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Sample records for current genetic vaccination

  1. [Current events in vaccination].

    PubMed

    Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C

    2011-11-01

    The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

  2. [Current events in vaccination].

    PubMed

    Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J L; Strady, C

    2011-05-01

    The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

  3. Genetically engineered vaccines.

    PubMed

    Thomas, Wayne R; Hales, Belinda J; Smith, Wendy-Anne

    2005-05-01

    The application of recombinant DNA technology to allergen research has provided the sequence information and genetic material to produce new types of allergy vaccines. One general strategy has been to use the knowledge to produce synthetic peptides that represent selected T-cell or B-cell epitopes. The production of genetically engineered allergens provides an alternative strategy to construct hypoallergenic vaccines, which can provide a better and less selected representation of the epitopes. Many strategies have been used to produce such hypoallergens, and their ability to reduce allergenicity has been amply demonstrated by skin and nasal provocation tests. The retention of T cell-stimulating activity has also been demonstrated, and a consistent feature of the vaccines has been, despite the reduced immunoglobulin E (IgE)-binding reactivity, the ability to induce anti-allergen IgG antibody. The lead hypoallergens have been polypeptide fragments and trimeric constructs of the birch allergen Bet v 1. A clinical trial with these medicaments has shown the ability to modify IgE and IgG antibody production, skin test reactivity, and symptom scores. This is the first trial of a recombinant allergy vaccine, and it has set a benchmark for further studies. A new generation of hypoallergens is now being produced based on the detailed knowledge of the tertiary structures of the allergens and of the T-cell and B-cell epitopes. The modifications have been made to change the topography of the allergens while retaining a stable, folding structure. In the case of Bet v 1, tertiary structures of hypoallergens have been determined. Structurally modeled hypoallergens have been produced for pollen, venom, food, and latex allergens, with promising characteristics from preclinical studies. PMID:15842957

  4. Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice.

    PubMed

    Rodrigues, Mauricio M; de Alencar, Bruna C; Claser, Carla; Tzelepis, Fanny; Silveira, Eduardo L; Haolla, Filipe A; Dominguez, Mariana R; Vasconcelos, José Ronnie

    2009-07-01

    Vaccines have had an unquestionable impact on public health during the last century. The most likely reason for the success of vaccines is the robust protective properties of specific antibodies. However, antibodies exert a strong selective pressure and many microorganisms, such as the obligatory intracellular parasite Trypanosoma cruzi, have been selected to survive in their presence. Although the host develops a strong immune response to T. cruzi, they do not clear the infection and instead progress to the chronic phase of the disease. Parasite persistence during the chronic phase of infection is now considered the main factor contributing to the chronic symptoms of the disease. Based on this finding, containment of parasite growth and survival may be one method to avoid the immunopathology of the chronic phase. In this context, vaccinologists have looked over the past 20 years for other immune effector mechanisms that could eliminate these antibody-resistant pathogens. We and others have tested the hypothesis that non-antibody-mediated cellular immune responses (CD4+ Th1 and CD8+ Tc1 cells) to specific parasite antigens/genes expressed by T. cruzi could indeed be used for the purpose of vaccination. This hypothesis was confirmed in different mouse models, indicating a possible path for vaccine development. PMID:19753486

  5. RNA Virus Reverse Genetics and Vaccine Design

    PubMed Central

    Stobart, Christopher C.; Moore, Martin L.

    2014-01-01

    RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. PMID:24967693

  6. Reverse genetics technology for Rift Valley fever virus: current and future applications for the development of therapeutics and vaccines.

    PubMed

    Bouloy, Michele; Flick, Ramon

    2009-11-01

    The advent of reverse genetics technology has revolutionized the study of RNA viruses, making it possible to manipulate their genomes and evaluate the effects of these changes on their biology and pathogenesis. The fundamental insights gleaned from reverse genetics-based studies over the last several years provide a new momentum for the development of designed therapies for the control and prevention of these viral pathogens. This review summarizes the successes and stumbling blocks in the development of reverse genetics technologies for Rift Valley fever virus and their application to the further dissection of its pathogenesis and the design of new therapeutics and safe and effective vaccines. PMID:19682499

  7. Current Status of Veterinary Vaccines

    PubMed Central

    Meeusen, Els N. T.; Walker, John; Peters, Andrew; Pastoret, Paul-Pierre; Jungersen, Gregers

    2007-01-01

    The major goals of veterinary vaccines are to improve the health and welfare of companion animals, increase production of livestock in a cost-effective manner, and prevent animal-to-human transmission from both domestic animals and wildlife. These diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations, and naked DNA injections. The final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace or that will be used in the field to achieve desired outcomes. As detailed in this review, successful veterinary vaccines have been produced against viral, bacterial, protozoal, and multicellular pathogens, which in many ways have led the field in the application and adaptation of novel technologies. These veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies and preventing animal-to-human transmission of infectious diseases. The continued interaction between animals and human researchers and health professionals will be of major importance for adapting new technologies, providing animal models of disease, and confronting new and emerging infectious diseases. PMID:17630337

  8. Current Vaccine Shortages and Delays

    MedlinePlus

    ... Patient Education Programs and Tools VTrckS (Vaccine Tracking System) Immunization Registries (IIS) Vaccines for Children (VFC) Stop Transmission of Polio (STOP) Vaccine Management Business Improvement Project (VMBIP) Global Immunizations & Vaccinations Immunization Program ...

  9. Fish Vaccines: Current State and Future Advances

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In aquaculture, the development and use of vaccines is now making rapid progress to achieve its full potential as an effective disease prevention tool. Currently, USDA, APHIS, CVB licenses 17 fish vaccines of which 2 are modified live and 14 are killed vaccines. The objective of vaccination is to pr...

  10. Current status and future prospects of yellow fever vaccines.

    PubMed

    Beck, Andrew S; Barrett, Alan D T

    2015-11-01

    Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized historically for its immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be lifelong. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease. PMID:26366673

  11. Japanese encephalitis vaccines: current vaccines and future prospects.

    PubMed

    Monath, T P

    2002-01-01

    Vaccination against JE ideally should be practiced in all areas of Asia where the virus is responsible for human disease. The WHO has placed a high priority on the development of a new vaccine for prevention of JE. Some countries in Asia (Japan, South Korea, North Korea, Taiwan, Vietnam, Thailand, and the PRC) manufacture JE vaccines and practice childhood immunization, while other countries suffering endemic or epidemic disease (India, Nepal, Laos, Cambodia, Bangladesh, Myanmar, Malaysia, Indonesia and the Philippines) have no JE vaccine manufacturing or policy for use. With the exception of the PRC, all countries practicing JE vaccination use formalin inactivated mouse brain vaccines, which are relatively expensive and are associated with rare but clinically significant allergic and neurological adverse events. New inactivated JE vaccines manufactured in Vero cells are in advanced preclinical or early clinical development in Japan, South Korea, Taiwan, and the PRC. An empirically derived, live attenuated vaccine (SA14-14-2) is widely used in the PRC. Trials in the PRC have shown SA14-14-2 to be safe and effective when administered in a two-dose regimen, but regulatory concerns over manufacturing and control have restricted international distribution. The genetic basis of attenuation of SA14-14-2 has been partially defined. A new live attenuated vaccine (ChimeriVax-JE) that uses a reliable flavivirus vaccine--yellow fever 17D--as a live vector for the envelope genes of SA14-14-2 virus is in early clinical trials and appears to be well tolerated and immunogenic after a single dose. Vaccinia and avipox vectored vaccines have also been tested clinically, but are no longer being pursued due to restricted effectiveness mediated by anti-vector immunity. Other approaches to JE vaccines--including naked DNA, oral vaccination, and recombinant subunit vaccines--have been reviewed. PMID:12082985

  12. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    PubMed Central

    Aurisicchio, Luigi; Ciliberto, Gennaro

    2011-01-01

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost. PMID:24212974

  13. Current progress in dengue vaccines

    PubMed Central

    2013-01-01

    Dengue is one of the most important emerging vector-borne viral diseases. There are four serotypes of dengue viruses (DENV), each of which is capable of causing self-limited dengue fever (DF) or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The major clinical manifestations of severe DENV disease are vascular leakage, thrombocytopenia, and hemorrhage, yet the detailed mechanisms are not fully resolved. Besides the direct effects of the virus, immunopathological aspects are also involved in the development of dengue symptoms. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, and live recombinant, DNA and subunit vaccines. The live attenuated virus vaccines and live chimeric virus vaccines are undergoing clinical evaluation. The other vaccine candidates have been evaluated in preclinical animal models or are being prepared for clinical trials. For the safety and efficacy of dengue vaccines, the immunopathogenic complications such as antibody-mediated enhancement and autoimmunity of dengue disease need to be considered. PMID:23758699

  14. Differential genetic variation of chickens and MD vaccine protective efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccine protective efficacy is determined by multiple factors including host genetics, the type of vaccine, vaccine dosage, the virulence and dose of challenging viruses, and the interval between vaccination and viral challenge. Studies on human immune responses to vaccinations suggest host genetic...

  15. Vaccine delivery--current trends and future.

    PubMed

    Azad, Neelam; Rojanasakul, Yon

    2006-04-01

    Since its discovery in 1796 by Edward Jenner, vaccines have been an integral aspect of therapeutics, combating a number of infectious diseases with remarkable success. In recent years, due to rapid advances in proteomics, genomics, biotechnology and immunology and the plethora of knowledge amassed in related fields, it is fair to expect vaccine development to progress at an exponential pace. However, as we march on into the 21st century, we are still struggling in our efforts to eradicate fatal diseases such as AIDS, malaria and hepatitis C due, in part, to the absence of effective vaccines against these diseases. Vaccine development faces major challenges both technologically and economically. Newer vaccines that are stable, economical, require fewer doses and can be administered using needle free systems are a worldwide priority. An ideal theoretical vaccine may not be cogent unless formulated and delivered aptly. Delivery of vaccines via oral, intranasal, transcutaneous and intradermal routes will decrease the risk of needle-borne diseases and may eliminate the need for trained personnel and sterile equipment. Crucial to the success of a vaccine is the delivery strategy that is to be employed. Currently, various techniques involving DNA vaccines, adjuvants, microparticles and transgenic plants are being developed and evaluated. Although, no major breakthrough is in prospect, these systems have potential and will take immunization to a new technological level. This review will focus on the current development of some novel vaccine delivery systems and will explore the non-parenteral routes of vaccine administration. PMID:16611000

  16. [Diarrhea and vaccines: current developments].

    PubMed

    Landry, P

    2006-05-10

    Diarrhoea is a main concern for travellers, populations of developing countries and children. Causative pathogens are numerous. An efficient vaccine against cholera is available, also offering a 50% cross-protection against E. Coli enterotoxin (ETEC), however its efficacy is only 23% against all-causes traveller's diarrhoea. Rotavirus can be responsible for severe diarrhoea in infants but rarely causes traveller's diarrhoea. Two new vaccines being under development appear effective and well-tolerated but too expensive for developing countries which most need them. To date, the live oral Ty21a vaccine remains frequently prescribed in Switzerland, with limited indications and suboptimal efficacy. A new oral vaccine is under development. PMID:16767878

  17. Current controversies in childhood vaccination.

    PubMed

    Carrillo-Marquez, Maria; White, Lisa

    2013-01-01

    As pediatric practitioners, one of the contemporary challenges in providing medical care for children is the increasing proportion of vaccination refusal. This occurs in spite of the demonstrated individual and collective benefit and cost effectiveness of vaccination. Controversies regarding vaccine components and side effects have misled parents to believe that vaccines might be harmful based on inaccurate data from the Internet, celebrities, as well as misinterpreted and frankly bad science. This belief of vaccines being harmful has led to fear and decreased immunization rates in spite of sound scientific evidence supporting the safety of vaccines and their lack of association with autism, developmental disabilities or other medical disorders. Some parents also believe in alternative ways to avoid disease, often adhering to practices that have little foundation in the best of empiric science. It is not a coincidence that recent outbreaks of vaccine-preventable diseases, including measles and pertussis (whooping cough), have occurred in areas where vaccination has declined largely due to exemptors. This article intends to review some of the common vaccine myths and controversies and to serve as a resource to provide accurate information and references for busy practitioners and the families that we serve. PMID:23444591

  18. Oral vaccination of raccoons (Procyon lotor) with genetically modified rabies virus vaccines

    PubMed Central

    Blanton, Jesse D.; Self, Joshua; Niezgoda, Michael; Faber, Marie-Luise; Dietzschold, Bernhard; Rupprecht, Charles

    2007-01-01

    Oral vaccination is an important tool currently in use to control the spread of rabies in wildlife populations in various programs around the world. Oral rabies vaccination (ORV) of raccoons represents the largest targeted program to control wildlife rabies in the United States. Currently, the vaccinia-rabies glycoprotein recombinant virus vaccine (V-RG) is the only licensed oral rabies vaccine in the US. In the current study, captive raccoons were used to evaluate two previously described constructs of a rabies virus vaccine developed by reverse genetics (SPBNGAS and SPBNGAS-GAS) for immunogenicity and efficacy compared to the V-RG vaccine. Four of five control animals succumbed to rabies virus after severe challenge, while three of five animals vaccinated orally with SPBNGAS succumbed. No mortality was observed for animals administered SPBNGAS-GAS or the V-RG vaccine. The results of this preliminary study suggest that SPBNGAS-GAS provides comparable efficacy to V-RG. Additional studies will be needed to determine the duration of immunity and optimal dosage of SPBNGAS-GAS and to examine its efficacy in other reservoir species. PMID:17826874

  19. Oral vaccination of raccoons (Procyon lotor) with genetically modified rabies virus vaccines.

    PubMed

    Blanton, Jesse D; Self, Joshua; Niezgoda, Michael; Faber, Marie-Luise; Dietzschold, Bernhard; Rupprecht, Charles

    2007-10-16

    Oral vaccination is an important tool currently in use to control the spread of rabies in wildlife populations in various programs around the world. Oral rabies vaccination (ORV) of raccoons represents the largest targeted program to control wildlife rabies in the United States. Currently, the vaccinia-rabies glycoprotein recombinant virus vaccine (V-RG) is the only licensed oral rabies vaccine in the US. In the current study, captive raccoons were used to evaluate two previously described constructs of a rabies virus vaccine developed by reverse genetics (SPBNGAS and SPBNGAS-GAS) for immunogenicity and efficacy compared to the V-RG vaccine. Four of five control animals succumbed to rabies virus after severe challenge, while three of five animals vaccinated orally with SPBNGAS succumbed. No mortality was observed for animals administered SPBNGAS-GAS or the V-RG vaccine. The results of this preliminary study suggest that SPBNGAS-GAS provides comparable efficacy to V-RG. Additional studies will be needed to determine the duration of immunity and optimal dosage of SPBNGAS-GAS and to examine its efficacy in other reservoir species. PMID:17826874

  20. HPV vaccine: Current status and future directions

    PubMed Central

    Kumar, Sushil; Biswas, Manash; Jose, Tony

    2015-01-01

    HPV Vaccine was introduced to prevent cervical cancer known to be caused by infection with one or more of the high risk subtypes of the Human papilloma virus (HPV). Since introduction, trials have proven its efficacy in preventing Cervical intraepithelial neoplasia (CIN) beyond doubt and its effectiveness in preventing cervical cancer though presumptive is reasonably certain as per mathematical modelling. It also prevents other HPV related anogenital and oropharyngeal malignancies in both sexes. HPV vaccines have courted many controversies related to its efficacy, safety, ideal age of vaccination, use in HPV infected individuals and use in males. The currently available vaccines are based on L1 Viral like particles (VLP) and hence highly species specific, thermolabile, costly and are purely prophylactic. The quest for a cheaper, thermostable and broad spectrum vaccine has led to many newer prophylactic vaccines. Therapeutic vaccines were born out of the inescapable necessity considering high HPV related morbidity projected in the non HPV naïve population. Therapeutic vaccines would immediately reduce this burden and also help in the management of HPV related cancers alone or as part of combination strategies. Ongoing research is aimed at a total control over HPV related malignancies in the near future. PMID:25859081

  1. Peptide vaccination is superior to genetic vaccination using a recombineered bacteriophage λ subunit vaccine.

    PubMed

    Thomas, Brad S; Nishikawa, Sandra; Ito, Kenichi; Chopra, Puja; Sharma, Navneet; Evans, David H; Tyrrell, D Lorne J; Bathe, Oliver F; Rancourt, Derrick E

    2012-02-01

    Genetic immunization holds promise as a vaccination method, but has so far proven ineffective in large primate and human trials. Herein, we examined the relative merits of genetic immunization and peptide immunization using bacteriophage λ. Bacteriophage λ has proven effective in immune challenge models using both immunization methods, but there has never been a direct comparison of efficacy and of the quality of immune response. In the current study, this vector was produced using a combination of cis and trans phage display. When antibody titers were measured from immunized animals together with IL-2, IL-4 and IFNγ production from splenocytes in vitro, we found that proteins displayed on λ were superior at eliciting an immune response in comparison to genetic immunization with λ. We also found that the antibodies produced in response to immunization with λ displayed proteins bound more epitopes than those produced in response to genetic immunization. Finally, the general immune response to λ inoculation, whether peptide or genetic, was dominated by a Th1 response, as determined by IFNγ and IL-4 concentration, or by a higher concentration of IgG2a antibodies. PMID:22210400

  2. Current status of human papillomavirus vaccines

    PubMed Central

    Yi, Seokjae

    2014-01-01

    Cervical cancer is a malignant neoplasm arising from cells that originate in the cervix uteri. It is the second most prevalent cancer among women. It can have several causes; an infection with some type of human papillomavirus (HPV) is the greatest risk factor for cervical cancer. Over 100 types of HPVs have been identified, and more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region. Among these, a number of HPVs types, containing types 16 and 18, are classified as "high-risk" HPVs that can cause cervical cancer. The HPVs vaccine prevents infection with certain species of HPVs associated with the development of cervical cancer, genital warts, and some less common cancers. Two HPVs vaccines are currently on the global market: quadrivalent HPVs vaccine and bivalent HPV vaccine that use virus-like particles as a vaccine antigen. This review discusses the current status of HPVs vaccines on the global market, clinical trials, and the future of HPVs vaccine development. PMID:25003090

  3. Leishmaniasis: Current Status of Vaccine Development

    PubMed Central

    Handman, Emanuela

    2001-01-01

    Leishmaniae are obligatory intracellular protozoa in mononuclear phagocytes. They cause a spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Worldwide, there are 2 million new cases each year and 1/10 of the world's population is at risk of infection. To date, there are no vaccines against leishmaniasis and control measures rely on chemotherapy to alleviate disease and on vector control to reduce transmission. However, a major vaccine development program aimed initially at cutaneous leishmaniasis is under way. Studies in animal models and humans are evaluating the potential of genetically modified live attenuated vaccines, as well as a variety of recombinant antigens or the DNA encoding them. The program also focuses on new adjuvants, including cytokines, and delivery systems to target the T helper type 1 immune responses required for the elimination of this intracellular organism. The availability, in the near future, of the DNA sequences of the human and Leishmania genomes will extend the vaccine program. New vaccine candidates such as parasite virulence factors will be identified. Host susceptibility genes will be mapped to allow the vaccine to be targeted to the population most in need of protection. PMID:11292637

  4. Bead-Selected Antitumor Genetic Cell Vaccines

    PubMed Central

    Herrero, MJ; R, Botella; R, Algás; Marco, FM; Aliño, SF

    2008-01-01

    Cancer vaccines have always been in the scope of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. However, to become a clinical reality, tumor cells must suffer a long and risky process from the extraction from the patient to the reimplantation as a vaccine. In this work, we explain our group’s approach to reduce the cell number required to achieve an immune response against a melanoma murine model, employing bead-selected B16 tumor cells expressing GM-CSF and B7.2. PMID:21892287

  5. Plague vaccines: current developments and future perspectives

    PubMed Central

    Feodorova, Valentina A; Motin, Vladimir L

    2012-01-01

    Despite many decades of intensive studies of Yersinia pestis, the causative agent of plague, there is no safe and efficient vaccine against this devastating disease. A recently developed F1/V subunit vaccine candidate, which relies mainly on humoral immunity, showed promising results in animal studies; however, its efficacy in humans still has to be carefully evaluated. In addition, those developing next-generation plague vaccines need to pay particular attention to the importance of eliciting cell-mediated immunity. In this review, we analyzed the current progress in developing subunit, DNA and live carrier platforms of delivery by bacterial and viral vectors, as well as approaches for controlled attenuation of virulent strains of Y. pestis. PMID:26038406

  6. Host genetic variation is a contributable factor for imperfectly-immunizing vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccine protective efficacy is determined by multiple factors including host genetics, vaccine type, vaccine dosage, challenge virus virulence, challenge virus dose, and interval between vaccination and exposure to challenge viruses. About two decades ago, studies conducted to evaluate host genetic ...

  7. Genetic engineering of live rabies vaccines.

    PubMed

    Morimoto, K; McGettigan, J P; Foley, H D; Hooper, D C; Dietzschold, B; Schnell, M J

    2001-05-14

    Rabies virus is not a single entity but consists of a wide array of variants that are each associated with different host species. These viruses differ greatly in the antigenic makeup of their G proteins, the primary determinant of pathogenicity and major inducer of protective immunity. Due to this diversity, existing rabies vaccines have largely been targeted to individual animal species. In this report, a novel approach to the development of rabies vaccines using genetically modified, reverse-engineered live attenuated rabies viruses is described. This approach entails the engineering of vaccine rabies virus containing G proteins from virulent strains and modification of the G protein to further reduce pathogenicity. Strategies employed included exchange of the arginine at position 333 for glutamine and modification of the cytoplasmic domain. The recombinant viruses obtained were non-neuroinvasive when administered via a peripheral route. The ability to confer protective immunity depended largely upon conservation of the G protein antigenic structure between the vaccine and challenge virus, as well as on the route of immunization. PMID:11348722

  8. Current status of Plasmodium vivax vaccine.

    PubMed

    Arévalo-Herrera, Myriam; Chitnis, Chetan; Herrera, Sócrates

    2010-01-01

    From a total of 2.6 billion people at permanent risk of suffering malaria infection worldwide, 80-300 million experience Plasmodium vivax infections every year, with clinical manifestations ranging from asymptomatic to mild and chronic infection that in some cases lead to severe disease and death. The increasing P. vivax drug resistance and reports of severe and lethal cases, the relapsing parasite behavior and the existence of Plasmodium spp. co-infections must prompt more investment and greater efforts for the development of P. vivax vaccine. Currently there are only two P. vivax vaccine candidates being tested in clinical trials and few others are being assessed in preclinical studies which contrast with the numerous P. falciparum vaccines candidates under evaluation. The recent availability of the P. vivax genome and ongoing proteomic analysis are likely to accelerate P. vivax vaccine development. Recent development of human sporozoite-challenge models would contribute to move clinical development forward and to identify mechanisms of immunity. PMID:20009526

  9. Current status and prospects for development of an HSV vaccine.

    PubMed

    Johnston, Christine; Koelle, David M; Wald, Anna

    2014-03-20

    Herpes simplex virus type 2 (HSV-2) infects 530million people, is the leading cause of genital ulcer disease, and increases the risk of HIV-1 acquisition. Although several candidate vaccines have been promising in animal models, prophylactic and therapeutic vaccines have not been effective in clinical trials thus far. Null results from the most recent prophylactic glycoprotein D2 subunit vaccine trial suggest that we must reevaluate our approach to HSV-2 vaccine development. We discuss HSV-2 pathogenesis, immunity, and vaccine efforts to date, as well as the current pipeline of candidate vaccines and design of trials to evaluate new vaccine constructs. PMID:24016811

  10. Emergency deployment of genetically engineered veterinary vaccines in Europe.

    PubMed

    Ramezanpour, Bahar; de Foucauld, Jean; Kortekaas, Jeroen

    2016-06-24

    On the 9th of November 2015, preceding the World Veterinary Vaccine Congress, a workshop was held to discuss how veterinary vaccines can be deployed more rapidly to appropriately respond to future epizootics in Europe. Considering their potential and unprecedented suitability for surge production, the workshop focussed on vaccines based on genetically engineered viruses and replicon particles. The workshop was attended by academics and representatives from leading pharmaceutical companies, regulatory experts, the European Medicines Agency and the European Commission. We here outline the present regulatory pathways for genetically engineered vaccines in Europe and describe the incentive for the organization of the pre-congress workshop. The participants agreed that existing European regulations on the deliberate release of genetically engineered vaccines into the environment should be updated to facilitate quick deployment of these vaccines in emergency situations. PMID:27208587

  11. [Influenza vaccination. Effectiveness of current vaccines and future challenges].

    PubMed

    Ortiz de Lejarazu, Raúl; Tamames, Sonia

    2015-01-01

    Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. PMID:26232121

  12. Use of a current varicella vaccine as a live polyvalent vaccine vector.

    PubMed

    Murakami, Kouki; Mori, Yasuko

    2016-01-01

    Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The varicella vaccine was developed to control VZV infection in children. The currently available Oka vaccine strain is the only live varicella vaccine approved by the World Health Organization. We previously cloned the complete genome of the Oka vaccine strain into a bacterial artificial chromosome vector and then successfully reconstituted the virus. We then used this system to generate a recombinant Oka vaccine virus expressing mumps virus gene(s). The new recombinant vaccine may be an effective polyvalent live vaccine that provides protection against both varicella and mumps viruses. In this review, we discussed about possibility of polyvalent live vaccine(s) using varicella vaccine based on our recent studies. PMID:25444800

  13. Limited genetic and antigenic diversity within parasite isolates used in a live vaccine against Theileria parva.

    PubMed

    Hemmink, Johanneke D; Weir, William; MacHugh, Niall D; Graham, Simon P; Patel, Ekta; Paxton, Edith; Shiels, Brian; Toye, Philip G; Morrison, W Ivan; Pelle, Roger

    2016-07-01

    An infection and treatment protocol is used to vaccinate cattle against Theileria parva infection. Due to incomplete cross-protection between different parasite isolates, a mixture of three isolates, termed the Muguga cocktail, is used for vaccination. While vaccination of cattle in some regions provides high levels of protection, some animals are not protected against challenge with buffalo-derived T. parva. Knowledge of the genetic composition of the Muguga cocktail vaccine is required to understand how vaccination is able to protect against field challenge and to identify the potential limitations of the vaccine. The aim of the current study was to determine the extent of genetic and antigenic diversity within the parasite isolates that constitute the Muguga cocktail. High throughput multi-locus sequencing of antigen-encoding loci was performed in parallel with typing using a panel of micro- and mini-satellite loci. The former focused on genes encoding CD8(+) T cell antigens, believed to be relevant to protective immunity. The results demonstrate that each of the three component stocks of the cocktail contains limited parasite genotypic diversity, with single alleles detected at many gene/satellite loci and, moreover, that two of the components show a very high level of similarity. Thus, the vaccine incorporates very little of the genetic and antigenic diversity observed in field populations of T. parva. The presence of alleles at low frequency (<10%) within vaccine component populations also points to the possibility of variability in the content of vaccine doses and the potential for loss of allelic diversity during tick passage. The results demonstrate that there is scope to modify the content of the vaccine in order to enhance its diversity and thus its potential for providing broad protection. The ability to accurately quantify genetic diversity in vaccine component stocks will facilitate improved quality control procedures designed to ensure the long

  14. A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens

    PubMed Central

    Daniels, Calvin C.; Rogers, P. David

    2016-01-01

    This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines. PMID:26997927

  15. A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens.

    PubMed

    Daniels, Calvin C; Rogers, P David; Shelton, Chasity M

    2016-01-01

    This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines. PMID:26997927

  16. Heterogeneity of porcine reproductive and respiratory syndrome virus: implications for current vaccine efficacy and future vaccine development.

    PubMed

    Meng, X J

    2000-06-12

    Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a major problem to the pork industry worldwide. Increasing data indicate that PRRSV strains differ in virulence in infected pigs and are biologically, antigenically, and genetically heterogeneous. It is evident that the current vaccines, based on a single PRRSV strain, are not effective in protecting against infections with the genetically diverse field strains of PRRSV. The recent outbreaks of atypical or acute PRRS in vaccinated pigs have raised a serious concern about the efficacy of the current vaccines and provided the impetus for developing more effective vaccines. Special attention in this review is given to published work on antigenic, pathogenic and genetic variations of PRRSV and its potential implications for vaccine efficacy and development. Although there are ample data documenting the heterogeneous nature of PRRSV strains, information regarding how the heterogeneity is generated and what clinical impact it may have is very scarce. The observed heterogeneity will likely pose a major obstacle for effective prevention and control of PRRS. There remains an urgent need for fundamental research on this virus to understand the basic biology and the mechanism of heterogeneity and pathogenesis of PRRSV. PMID:10831854

  17. Current aspects of vitiligo genetics

    PubMed Central

    Męcińska-Jundziłł, Kaja

    2014-01-01

    Vitiligo is a common acquired depigmentation disorder of the skin manifested by the presence of white macules. The disease occurs at a frequency of approximately 1–4% of the world population. Currently, the most popular theory of vitiligo development is a multifactorial hypothesis according to which genetic conditions predispose vitiligo macules to occur as a result of specific environmental factors. According to the genetic hypothesis, vitiligo inheritance is multigenic. Genetic studies conducted so far concern patients with non-segmental vitiligo. There are three basic techniques of genetic studies: candidate gene association studies, genomewide linkage studies and genome-wide association studies (GWAS). The GWAS are the “gold standard” for detecting susceptibility genes. Up to now, approximately 36 convincing non-segmental vitiligo susceptibility loci have been identified. Approximately 90% of them encode immunoregulatory proteins, while approximately 10% encode melanocyte proteins. The existence of various associations between vitiligo and other autoimmune diseases may provide new knowledge on the causes of many disorders. Examples include the inverse relationship between vitiligo and melanoma and association of vitiligo with other autoimmune diseases. The main goal of all researches is to find new, optimal therapeutic strategies for vitiligo and other autoimmune diseases. PMID:25254010

  18. Review: New Vaccine Against Tuberculosis: Current Developments and Future Challenges

    NASA Astrophysics Data System (ADS)

    Liu, Jun

    2009-04-01

    Tuberculosis (TB) continues to be a global health threat. BCG was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, BCG is not an ideal vaccine and has two major limitations: its poor efficacy against adult pulmonary TB and its disconcerting safety in immunocompromised individuals. A safer and more effective TB vaccine is urgently needed. This review article discusses current strategies to develop the next generation of TB vaccines to replace BCG. While some progresses have been made in the past decade, significant challenges lie ahead.

  19. The history of vaccination and current vaccination policies in Korea

    PubMed Central

    2012-01-01

    There may be many reasons for the significant decrease in the incidence of the pediatric infectious diseases in modern Korea; this could be due to the improvement of sanitary facilities, significant growth of Korean economy, improvement of nutrition, development and dissemination of antibiotics and implantation of vaccination, and overall improvement of medical technology. The development of vaccination has been highlighted as a striking achievement of the modern medical sciences with new technologies in many fields of medicine. Since 1876, the method for vaccination has opened its new era by Suk-Young Jee, known as the Jenner in Korea who wrote a book about smallpox vaccination, and it led an opportunity to propagate the needs for the vaccination in Korea. There was a time when pediatric wards were full of patients with parasitic diseases and many vaccine-preventable diseases such as diphtheria, pertussis, Japanese B encephalitis, and poliomyelitis in 1950s-1960s. We do not see those infectious diseases that often any more in recent years. However, we still have patients with water-borne diseases and other communicable diseases related to increasing international travels. We just experienced the first pandemic influenza of the 21st century in 2009 and avian influenza is still a threat to humans in other parts of the world with an unpredictable potential of pandemicity. In addition, we have tough battles with emerging antibiotic resistance in many strains of bacteria and increased opportunistic infections due to improvement of medical technology involving more aggressive treatment modality and use of medical devices. Researches in many areas are under way and we hope that some of them may be preventable and decreased with a development of new vaccines in the future. PMID:23596573

  20. Dengue vaccines: challenges, development, current status and prospects.

    PubMed

    Ghosh, A; Dar, L

    2015-01-01

    Infection with dengue virus (DENV) is the most rapidly spreading mosquito-borne viral disease in the world. The clinical spectrum of dengue, caused by any of the four serotypes of DENV, ranges from mild self-limiting dengue fever to severe dengue, in the form dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Increased rates of hospitalization due to severe dengue, during outbreaks, result in massive economic losses and strained health services. In the absence of specific antiviral therapy, control of transmission of DENV by vector management is the sole method available for decreasing dengue-associated morbidity. Since vector control strategies alone have not been able to satisfactorily achieve reduction in viral transmission, the implementation of a safe, efficacious and cost-effective dengue vaccine as a supplementary measure is a high public health priority. However, the unique and complex immunopathology of dengue has complicated vaccine development. Dengue vaccines have also been challenged by critical issues like lack of animal models for the disease and absence of suitable markers of protective immunity. Although no licensed dengue vaccine is yet available, several vaccine candidates are under phases of development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored vaccines. Although some vaccine candidates have progressed from animal trials to phase II and III in humans, a number of issues regarding implementation of dengue vaccine in countries like India still need to be addressed. Despite the current limitations, collaborative effects of regulatory bodies like World Health Organization with vaccine manufacturers and policy makers, to facilitate vaccine development and standardize field trials can make a safe and efficacious dengue vaccine a reality in near future. PMID:25559995

  1. Will the current measles vaccines ever eradicate measles?

    PubMed

    Stephenson, John

    2002-10-01

    Measles virus is the most infectious transmissible agent causing human disease and has probably been responsible for the deaths of more children than any other single cause. In addition, infection with the natural virus causes many severe complications, including encephalitis, deafness and pneumonia. The introduction of live attenuated vaccines, either singly or as the measles-mumps-rubella combined vaccine, has dramatically reduced the occurrence of disease and in countries where vaccine uptake is high, indigenous disease has been virtually eliminated. Even though the current vaccines are very efficient, they do have their limitations. Children are most at risk during the first year of life and for most of this period, maternal antibodies prevent effective immunization. In addition, the current measles vaccines are relatively heat labile which causes difficulty in tropical areas. In recent years, vaccination rates in some industrial countries have been adversely affected by fears that measles vaccines are linked to inflammatory bowel diseases and autism. Although there is no conclusive evidence to support these fears, they still remain and probably contribute to poor vaccine uptake in some regions and sections of society. Although severe complications from vaccination are extremely rare, mild local reactions are more common. Consequently, in countries where measles is declining or has been eliminated, the fear of side effects of vaccination may encourage the development of vaccines that do not rely on virus replication to take effect. PMID:12901574

  2. Genetics and Vaccines in the Era of Personalized Medicine

    PubMed Central

    Castiblanco, John; Anaya, Juan-Manuel

    2015-01-01

    Vaccines represent the most successful and sustainable tactic to prevent and counteract infection. A vaccine generally improves immunity to a particular disease upon administration by inducing specific protective and efficient immune responses in all of the receiving population. The main known factors influencing the observed heterogeneity for immune re-sponses induced by vaccines are gender, age, co-morbidity, immune system, and genetic background. This review is mainly focused on the genetic status effect to vaccine immune responses and how this could contribute to the development of novel vaccine candidates that could be better directed and predicted relative to the genetic history of an individual and/or population. The text offers a brief history of vaccinology as a field, a description of the genetic status of the most relevant and studied genes and their functionality and correlation with exposure to specific vaccines; followed by an inside look into autoimmunity as a concern when designing vaccines as well as perspectives and conclusions looking towards an era of personalized and predictive vaccinology instead of a one size fits all approach. PMID:25937813

  3. Genetics and vaccines in the era of personalized medicine.

    PubMed

    Castiblanco, John; Anaya, Juan-Manuel

    2015-02-01

    Vaccines represent the most successful and sustainable tactic to prevent and counteract infection. A vaccine generally improves immunity to a particular disease upon administration by inducing specific protective and efficient immune responses in all of the receiving population. The main known factors influencing the observed heterogeneity for immune re-sponses induced by vaccines are gender, age, co-morbidity, immune system, and genetic background. This review is mainly focused on the genetic status effect to vaccine immune responses and how this could contribute to the development of novel vaccine candidates that could be better directed and predicted relative to the genetic history of an individual and/or population. The text offers a brief history of vaccinology as a field, a description of the genetic status of the most relevant and studied genes and their functionality and correlation with exposure to specific vaccines; followed by an inside look into autoimmunity as a concern when designing vaccines as well as perspectives and conclusions looking towards an era of personalized and predictive vaccinology instead of a one size fits all approach. PMID:25937813

  4. [Rabies vaccines: Current status and prospects for development].

    PubMed

    Starodubova, E S; Preobrazhenskaia, O V; Kuzmenko, Y V; Latanova, A A; Yarygina, E I; Karpov, V L

    2015-01-01

    Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. Since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. Progress in molecular biology and biotechnology enabled the development of effective and safe technologies of vaccine production. Currently, new-generation vaccines are being developed based on recombinant rabies virus strains or on the production of an individual recombinant rabies antigen-glycoprotein (G protein), either as a component of nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this review, the main modern trends in the development of rabies vaccines have been discussed. PMID:26299857

  5. Current status of new tuberculosis vaccine in children.

    PubMed

    Pang, Yu; Zhao, Aihua; Cohen, Chad; Kang, Wanli; Lu, Jie; Wang, Guozhi; Zhao, Yanlin; Zheng, Suhua

    2016-04-01

    Pediatric tuberculosis contributes significantly to the burden of TB disease worldwide. In order to achieve the goal of eliminating TB by 2050, an effective TB vaccine is urgently needed to prevent TB transmission in children. BCG vaccination can protect children from the severe types of TB such as TB meningitis and miliary TB, while its efficacy against pediatric pulmonary TB ranged from no protection to very high protection. In recent decades, multiple new vaccine candidates have been developed, and shown encouraging safety and immunogenicity in the preclinical experiments. However, the limited data on protective efficacy in infants evaluated by clinical trials has been disappointing, an example being MVA85A. To date, no vaccine has been shown to be clinically safer and more effective than the presently licensed BCG vaccine. Hence, before a new vaccine is developed with more promising efficacy, we must reconsider how to better use the current BCG vaccine to maximize its effectiveness in children. PMID:27002369

  6. Dengue vaccines: recent developments, ongoing challenges and current candidates

    PubMed Central

    McArthur, Monica A.; Sztein, Marcelo B.; Edelman, Robert

    2013-01-01

    Summary Dengue is among the most prevalent and important arbovirus diseases of humans. In order to effectively control this rapidly spreading disease, control of the vector mosquito and a safe and efficacious vaccine are critical. Despite considerable efforts, the development of a successful vaccine has remained elusive. Multiple factors have complicated the creation of a successful vaccine, not the least of which are the complex, immune-mediated responses against four antigenically distinct serotypes necessitating a tetravalent vaccine providing long lasting protective immunity. Despite the multiple impediments, there are currently many promising vaccine candidates in pre-clinical and clinical development. Here we review the recent advances in dengue virus vaccine development and briefly discuss the challenges associated with the use of these vaccines as a public health tool. PMID:23984962

  7. Fish Vaccines: Current State and Future Trends

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A vaccine is a preventive tool used in a health management strategy for the control of infectious diseases. For more than 100 years, vaccines have proved to be effective for preventing infectious disease outbreaks in humans, poultry and other food animals. In aquaculture, the development and use of...

  8. Fish Vaccines: Current State and Future Trends

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A vaccine is a preventive tool used in a health management strategy for the control of infectious diseases. For more than 100 years, vaccines have proved to be effective for preventing infectious disease outbreaks in humans, poultry and other food animals. In aquaculture, the development and use o...

  9. Tick vaccines: current status and future directions.

    PubMed

    de la Fuente, José; Contreras, Marinela

    2015-01-01

    Ticks and tick-borne diseases are a growing problem affecting human and animal health worldwide. Traditional control methods, based primarily on chemical acaricides, have proven not to be sustainable because of the selection of acaricide-resistant ticks. Tick vaccines appear to be a promising and effective alternative for control of tick infestations and pathogen transmission. The purpose of this review is to summarize previous tick vaccine development and performance and formulate critical issues and recommendations for future directions for the development of improved and effective tick vaccines. The development of effective screening platforms and algorithms using omics approaches focused on relevant biological processes will allow the discovery of new tick-protective antigens. Future vaccines will likely combine tick antigens with different protective mechanisms alone or pathogen-derived antigens. The application of tick vaccines as a part of integrated control strategies will ultimately result in the control of tick-borne diseases. PMID:26289976

  10. Current status of vaccines against infectious bursal disease.

    PubMed

    Müller, Hermann; Mundt, Egbert; Eterradossi, Nicolas; Islam, M Rafiqul

    2012-01-01

    Infectious bursal disease virus (IBDV) is the aetiological agent of the acute and highly contagious infectious bursal disease (IBD) or "Gumboro disease". IBD is one of the economically most important diseases that affects commercially produced chickens worldwide. Along with strict hygiene management of poultry farms, vaccination programmes with inactivated and live attenuated viruses have been used to prevent IBD. Live vaccines show a different degree of attenuation; many of them may cause bursal atrophy and thus immunosuppression with poor immune response to vaccination against other pathogens and an increase in vulnerability to various types of infections as possible consequences. Depending on their intrinsic characteristics or on the vaccination procedures, some of the vaccines may not induce full protection against the very virulent IBDV strains and antigenic variants observed in the last three decades. As chickens are most susceptible to IBDV in their first weeks of life, active immunity to the virus has to be induced early after hatching. However, maternally derived IBDV-specific antibodies may interfere with early vaccination with live vaccines. Thus new technologies and second-generation vaccines including rationally designed and subunit vaccines have been developed. Recently, live viral vector vaccines have been licensed in several countries and are reaching the market. Here, the current status of IBD vaccines is discussed. PMID:22515532

  11. Genetic stability of vaccine strain Salmonella Typhi Ty21a over 25 years.

    PubMed

    Kopecko, Dennis J; Sieber, Heike; Ures, Jose A; Fürer, Andreas; Schlup, Jacqueline; Knof, Ulrich; Collioud, Andre; Xu, Deqi; Colburn, Kevin; Dietrich, Guido

    2009-04-01

    The attenuated live bacterial vaccine strain Salmonella enterica Serovar Typhi Ty21a is the main constituent of Vivotif, the only licensed oral vaccine against typhoid fever. The strain was developed in the 1970s by chemical mutagenesis. In the course of this mutagenesis, a number of mutations were introduced into the vaccine strain. Characterisation of the vaccine strain during development as well as release of master- and working seed lots (MSL and WSL) and commercial batches is based on phenotypic assays assessing microbiological and biochemical characteristics of Ty21a. In the current study, we have analysed by DNA sequencing the specific mutations originally correlated with the attenuation of strain Ty21a. These data demonstrate the stability of these mutations for MSLs and WSLs of Ty21a produced between 1980 and 2005. Finally, we have confirmed the correlation of these genetic mutations with the expected phenotypic attenuations for the seed lots used in vaccine manufacture over 25 years. PMID:19121604

  12. Human papilloma virus vaccines: Current scenario.

    PubMed

    Pandhi, Deepika; Sonthalia, Sidharth

    2011-07-01

    Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection with an estimated worldwide prevalence of 9-13% and approximately 6 million people being infected each year. Mostly acquired during adolescence or young adulthood, HPV presents clinically as anogenital warts and may progress to precancerous lesions and cancers of the cervix, vagina, vulva, penis and anus, and oropharynx. HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40-60% of vulvar, vaginal, and penile cancers. At present, two prophylactic HPV vaccines are commercially available and both are prepared from purified L1 structural proteins. These proteins self-assemble to form virus-like particles that induce a protective immunity. Gardasil(®) is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9-26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9-26 years of age for the prevention of genital warts. Cervarix™ is a bivalent vaccine approved for the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18, in females 10-25 years. HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer. The vaccines are most effective when given before the onset of sexual activity and provide long-term protection. Effective vaccination coverage in young adolescent females will substantially reduce the incidence of these anogenital malignancy-related morbidity and mortality. There is need to generate India-specific data on HPV epidemiology and HPV vaccination efficacy as well as continue worldwide surveillance and development of newer vaccines. PMID:22021967

  13. Current Trends in Antifertility Vaccine Research

    PubMed Central

    Moore, Donald E.; Covey, Dana C.; O'Brien, Kelvin D.

    1985-01-01

    We review the major advances that have recently occurred in the area of antifertility vaccines by examining the immunogenic potential of gamete, embryonic and placental antigens. In human trials using β-human chorionic gonadotropin coupled with tetanus toxoid as the immunogen, the major problems with antifertility vaccines relate to specificity and maintaining an adequate antibody titer to disrupt gestation. Possible complications include cross-reaction with other body tissues, immune complex deposition, cytotoxicity, impaired immunologic tumor surveillance and nonreversibility. PMID:3892913

  14. Current status of vaccine development for tularemia preparedness

    PubMed Central

    Hong, Kee-Jong; Park, Pil-Gu; Seo, Sang-Hwan; Rhie, Gi-eun

    2013-01-01

    Tularemia is a high-risk infectious disease caused by Gram-negative bacterium Francisella tularensis. Due to its high fatality at very low colony-forming units (less than 10), F. tularensis is considered as a powerful potential bioterrorism agent. Vaccine could be the most efficient way to prevent the citizen from infection of F. tularensis when the bioterrorism happens, but officially approved vaccine with both efficacy and safety is not developed yet. Research for the development of tularemia vaccine has been focusing on the live attenuated vaccine strain (LVS) for long history, still there are no LVS confirmed for the safety which should be an essential factor for general vaccination program. Furthermore the LVS did not show protection efficacy against high-risk subspecies tularensis (type A) as high as the level against subspecies holarctica (type B) in human. Though the subunit or recombinant vaccine candidates have been considered for better safety, any results did not show better prevention efficacy than the LVS candidate against F. tularensis infection. Currently there are some more trials to develop vaccine using mutant strains or nonpathogenic F. novicida strain, but it did not reveal effective candidates overwhelming the LVS either. Difference in the protection efficacy of LVS against type A strain in human and the low level protection of many subunit or recombinant vaccine candidates lead the scientists to consider the live vaccine development using type A strain could be ultimate answer for the tularemia vaccine development. PMID:23596588

  15. History of vaccines and positioning of current trends.

    PubMed

    Payette, P J; Davis, H L

    2001-11-01

    The history of vaccine development spans a relatively short period of time in comparison to the history of human civilization. However, monumental advances in the field of vaccines have been made in effort to combat infectious disease. These advances have led to a reduction, and in one case the complete eradication, of the burden of some infectious diseases of the world. Throughout the history of vaccine development, milestone discoveries can be identified that have shaped the field of vaccine development, as we know it. These milestones include the first official use of a vaccine by Edward Jenner, the attenuation principals observed by Pasteur, the development of cell culture for the propagation of viruses, and the production of first recombinant protein based vaccine for hepatitis B. As vaccine development progresses into the 21st century, it will be important to build on the experience and knowledge generated in the past, in an effort to surpass the limitations that currently hamper the development of new and more effective vaccine technologies. Presented here is an overview on the history of vaccine development and its influence on the positioning of current trends and future considerations. PMID:12455398

  16. Current developments in avian influenza vaccines, including safety of vaccinated birds as food.

    PubMed

    Swayne, D E; Suarez, D L

    2007-01-01

    Until recently, most vaccines against avian influenza were based on oil-emulsified inactivated low- or high-pathogenicity viruses. Now, recombinant fowl pox and avian paramyxovirus type 1 vaccines with avian influenza H5 gene inserts (+ or - N1 gene insert) are available and licensed. New technologies might overcome existing limitations to make available vaccines that can be grown in tissue culture systems for more rapid production; provide optimized protection, as a result of closer genetic relations to field viruses; allow mass administration by aerosol, in drinking-water or in ovo; and allow easier strategies for identifying infected birds within vaccinated populations (DIVA). The technologies include avian influenza viruses with partial gene deletions, avian influenza-Newcastle disease virus chimeras, vectored vaccines such as adenoviruses and Marek's disease virus, and subunit vaccines. These new methods should be licensed only after their purity, safety, efficacy and potency against avian influenza viruses have been demonstrated, and, for live vectored vaccines, restriction of viral transmission to unvaccinated birds. Use of vaccines in countries affected by highly pathogenic avian influenza will not only protect poultry but will provide additional safety for consumers. Experimental studies have shown that birds vaccinated against avian influenza have no virus in meat and minimal amounts in eggs after HPAI virus challenge, and that replication and shedding from their respiratory and alimentary tracts is greatly reduced. PMID:18411943

  17. Vaccination coverage of children with rare genetic diseases and attitudes of their parents toward vaccines.

    PubMed

    Esposito, Susanna; Cerutti, Marta; Milani, Donatella; Menni, Francesca; Principi, Nicola

    2016-03-01

    Despite the fact that the achievement of appropriate immunization coverage for routine vaccines is a priority for health authorities worldwide, vaccination delays or missed opportunities for immunization are common in children with chronic diseases. The main aim of this cross-sectional study was to evaluate immunization coverage and the timeliness of vaccination in children suffering from 3 different rare genetic diseases: Rubinstein-Taybi syndrome (RSTS), Sotos syndrome (SS), and Beckwith-Wiedemann syndrome (BWS). A total of 57 children with genetic diseases (15 with RSTS, 14 children with SS, and 28 with BWS) and 57 healthy controls with similar characteristics were enrolled. The coverage of all the recommended vaccines in children with genetic syndromes was significantly lower than that observed in healthy controls (p < 0.05 for all the comparisons). However, when vaccinated, all of the patients, independent of the genetic syndrome from which they suffer, were administered the primary series and the booster doses at a similar time to healthy controls. In comparison with parents of healthy controls, parents of children with genetic diseases were found to more frequently have negative attitudes toward vaccination (p < 0.05 for all the comparisons), mainly for fear of the emergence of adverse events or deterioration of the underlying disease. This study shows that vaccination coverage is poor in pediatric patients with RSTS, BWS, and SS and significantly lower than that observed in healthy children. These results highlight the need for educational programs specifically aimed at both parents and pediatricians to increase immunization coverage in children with these rare genetic diseases. PMID:26337545

  18. Therapeutic Cancer Vaccines: Current Status and Moving Forward

    PubMed Central

    2012-01-01

    Concurrent with US Food and Drug Administration (FDA) approval of the first therapeutic cancer vaccine, a wide spectrum of other cancer vaccine platforms that target a diverse range of tumor-associated antigens is currently being evaluated in randomized phase II and phase III trials. The profound influence of the tumor microenvironment and other immunosuppressive entities, however, can limit the effectiveness of these vaccines. Numerous strategies are currently being evaluated both preclinically and clinically to counteract these immunosuppressive entities, including the combined use of vaccines with immune checkpoint inhibitors, certain chemotherapeutics, small-molecule targeted therapies, and radiation. The potential influence of the appropriate patient population and clinical trial endpoint in vaccine therapy studies is discussed, as well as the potential importance of biomarkers in future directions of this field. PMID:22395641

  19. Current state in the development of candidate therapeutic HPV vaccines.

    PubMed

    Yang, Andrew; Jeang, Jessica; Cheng, Kevin; Cheng, Ting; Yang, Benjamin; Wu, T-C; Hung, Chien-Fu

    2016-08-01

    The identification of human papillomavirus (HPV) as an etiological factor for HPV-associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines. PMID:26901118

  20. Therapeutic human papillomavirus vaccines: current clinical trials and future directions

    PubMed Central

    Hung, Chien-Fu; Ma, Barbara; Monie, Archana; Tsen, Shaw-Wei; Wu, T-C

    2011-01-01

    Background Cervical cancer is the second largest cause of cancer deaths in women worldwide. It is now evident that persistent infection with high-risk human papillomavirus (HPV) is necessary for the development and maintenance of cervical cancer. Thus, effective vaccination against HPV represents an opportunity to restrain cervical cancer and other important cancers. The FDA recently approved the HPV vaccine Gardasil for the preventive control of HPV, using HPV virus-like particles (VLP) to generate neutralizing antibodies against major capsid protein, L1. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and HPV-associated lesions. Furthermore, due to the considerable burden of HPV infections worldwide, it would take decades for preventive vaccines to affect the prevalence of cervical cancer. Thus, in order to speed up the control of cervical cancer and treat current infections, the continued development of therapeutic vaccines against HPV is critical. Therapeutic HPV vaccines can potentially eliminate pre-existing lesions and malignant tumors by generating cellular immunity against HPV-infected cells that express early viral proteins such as E6 and E7. Objective This review discusses the future directions of therapeutic HPV vaccine approaches for the treatment of established HPV-associated malignancies, with emphasis on current progress of HPV vaccine clinical trials. Methods Relevant literature is discussed. Results/conclusion Though their development has been challenging, many therapeutic HPV vaccines have been shown to induce HPV-specific antitumor immune responses in preclinical animal models and several promising strategies have been applied in clinical trials. With continued progress in the field of vaccine development, HPV therapeutic vaccines may provide a potentially promising approach for the control of lethal HPV-associated malignancies. PMID:18352847

  1. Development of improved vaccines against whooping cough: current status.

    PubMed

    Marzouqi, Ibrahim; Richmond, Peter; Fry, Scott; Wetherall, John; Mukkur, Trilochan

    2010-07-01

    Prior to the introduction of killed whole cell pertussis vaccine [wP] in the 1940s, whooping cough was a major cause of infant death worldwide. Widespread vaccination of children with this vaccine caused a significant reduction in mortality. However in the 1990s and now more recently, there has been a resurgence of pertussis in several countries even in populations previously vaccinated with an acellular pertussis vaccine [aP]. In this review, we describe the epidemiology of whooping cough, the vast array of virulence factors produced by this pathogen potentially contributing to the resurgence of pertussis even in previously vaccinated populations of infants and children, history of whooping cough prophylaxis, possible mechanisms of immunity, lack of availability of a suitable non-toxic adjuvant capable of inducing both arms of the immune response, and the current status of development of improved vaccines with potential to induce longer-lasting protection, than is currently possible with the wP or aP vaccines, against whooping cough. PMID:20448470

  2. Biological safety concepts of genetically modified live bacterial vaccines.

    PubMed

    Frey, Joachim

    2007-07-26

    Live vaccines possess the advantage of having access to induce cell-mediated and antibody-mediated immunity; thus in certain cases they are able to prevent infection, and not only disease. Furthermore, live vaccines, particularly bacterial live vaccines, are relatively cheap to produce and easy to apply. Hence they are suitable to immunize large communities or herds. The induction of both cell-mediated immunity as well as antibody-mediated immunity, which is particularly beneficial in inducing mucosal immune responses, is obtained by the vaccine-strain's ability to colonize and multiply in the host without causing disease. For this reason, live vaccines require attenuation of virulence of the bacterium to which immunity must be induced. Traditionally attenuation was achieved simply by multiple passages of the microorganism on growth medium, in animals, eggs or cell cultures or by chemical or physical mutagenesis, which resulted in random mutations that lead to attenuation. In contrast, novel molecular methods enable the development of genetically modified organisms (GMOs) targeted to specific genes that are particularly suited to induce attenuation or to reduce undesirable effects in the tissue in which the vaccine strains can multiply and survive. Since live vaccine strains (attenuated by natural selection or genetic engineering) are potentially released into the environment by the vaccinees, safety issues concerning the medical as well as environmental aspects must be considered. These involve (i) changes in cell, tissue and host tropism, (ii) virulence of the carrier through the incorporation of foreign genes, (iii) reversion to virulence by acquisition of complementation genes, (iv) exchange of genetic information with other vaccine or wild-type strains of the carrier organism and (v) spread of undesired genes such as antibiotic resistance genes. Before live vaccines are applied, the safety issues must be thoroughly evaluated case-by-case. Safety assessment

  3. Poliomyelitis in the United States: A Historical Perspective and Current Vaccination Policy.

    ERIC Educational Resources Information Center

    Farizo, Karen M.; And Others

    1990-01-01

    Examines poliomyelitis in the United States by reviewing clinical manifestations and outcomes, history, recent epidemiologic characteristics, characteristics of currently available vaccines, controversies surrounding vaccination policy, current poliovirus vaccination recommendations, and prospects for worldwide eradication. Poliomyelitis remains…

  4. [New vaccines in the age of genetic engineering].

    PubMed

    Nolte, F

    1993-10-01

    The era of genetic engineering is merely 20 years of age, yet has already borne completely new perspectives for vaccine development. Important insights are gained by elucidating the genetic information of a disease-causing microorganism and its pathogenic and attenuated variants. Site-directed mutagenesis can then be employed to specifically alter the genetic information in a variety of ways. Upon transfer of the corresponding gene to pro- or eucaryotic cells, large quantities of microbial components can be produced. A new generation of such subunit vaccines is already undergoing clinical testing. Recently, hybrid vaccines have been constructed, which utilize highly successful traditional live vaccines such as polio- and vaccinia-virus or the Tbc-bacterium as carriers for components of other microorganisms. We should bear in mind that the same new technologies can be abused for the construction of potentially dangerous biological weapons. The scientific community bears the responsibility to prevent such abuse and to lobby for an easy access to the new vaccines by the world's poorest inhabitants. PMID:8253480

  5. Second-generation prophylactic HPV vaccines: current options and future strategies for vaccines development.

    PubMed

    Fruscalzo, Arrigo; Londero, Ambrogio P; Bertozzi, Serena; Lellè, Ralf J

    2016-02-01

    Two vaccines focused on the prevention of HPV-related diseases have been introduced in the last decade, the quadrivalent vaccine Gardasil and the bivalent vaccine Cervarix. They are targeted to prevent precancerous and cancerous lesions not only of the cervix, but also of the vulva, vagina, anal and head-neck region. Furthermore, the protection of the quadrivalent vaccine Gardasil includes also genital warts and recurrent respiratory Papillomatosis, two benign conditions with high socio-economic impact. Although their efficacy in reducing the burden of HPV-related pathologies has been already documented, second-generation HPV vaccines are being developed in order to overcome major limitations, above all the cost of production, distribution and acceptance, thus promoting an easier access to vaccination, especially in developing countries. Recently a new multivalent VLP vaccine active against nine HPV subtypes, called Gardasil 9 (Merck & Co., Inc., Whitehouse Station, NJ, USA), has been approved, showing promising preliminary results. In this article, we outline the strategies adopted for second-generation HPV vaccine engineering, the latest HPV vaccines available at this time, as well as those currently in development. PMID:26473283

  6. Current progress in development of hepatitis C virus vaccines.

    PubMed

    Liang, T Jake

    2013-07-01

    Despite major advances in the understanding and treatment of hepatitis C, a preventive vaccine remains elusive. The marked genetic diversity and multiple mechanisms of persistence of hepatitis C virus, combined with the relatively poor immune response of the infected host against the virus, are major barriers. The lack of robust and convenient model systems further hampers the effort to develop an effective vaccine. Advances in our understanding of virus-host interactions and protective immunity in hepatitis C virus infection provide an important roadmap to develop potent and broadly directed vaccine candidates targeting both humoral and cellular immune responses. Multiple approaches to generating and testing viral immunogens have met with variable success. Several candidates have advanced to clinical trials based on promising results in chimpanzees. The ultimate path to a successful preventive vaccine requires comprehensive evaluations of all aspects of protective immunity, innovative application of state-of-the-art vaccine technology and properly designed vaccine trials that can affirm definitive endpoints of efficacy. PMID:23836237

  7. Live vaccines for human metapneumovirus designed by reverse genetics.

    PubMed

    Buchholz, Ursula J; Nagashima, Kunio; Murphy, Brian R; Collins, Peter L

    2006-10-01

    Human metapneumovirus (HMPV) was first described in 2001 and has quickly become recognized as an important cause of respiratory tract disease worldwide, especially in the pediatric population. A vaccine against HMPV is required to prevent severe disease associated with infection in infancy. The primary strategy is to develop a live-attenuated virus for intranasal immunization, which is particularly well suited against a respiratory virus. Reverse genetics provides a means of developing highly characterized 'designer' attenuated vaccine candidates. To date, several promising vaccine candidates have been developed, each using a different mode of attenuation. One candidate involves deletion of the G glycoprotein, providing attenuation that is probably based on reduced efficiency of attachment. A second candidate involves deletion of the M2-2 protein, which participates in regulating RNA synthesis and whose deletion has the advantageous property of upregulating transcription and increasing antigen synthesis. A third candidate involves replacing the P protein gene of HMPV with its counterpart from the related avian metapneumovirus, thereby introducing attenuation owing to its chimeric nature and host range restriction. Another live vaccine strategy involves using an attenuated parainfluenza virus as a vector to express HMPV protective antigens, providing a bivalent pediatric vaccine. Additional modifications to provide improved vaccines will also be discussed. PMID:17181442

  8. Genetically engineered Mengo virus vaccination of multiple captive wildlife species.

    PubMed

    Backues, K A; Hill, M; Palmenberg, A C; Miller, C; Soike, K F; Aguilar, R

    1999-04-01

    Encephalomyocarditis virus (EMCV), has caused the deaths of many species of animals in zoological parks and research institutions. The Audubon Park Zoo, (New Orleans, Louisiana, USA) attempted vaccination of several species with a killed EMCV vaccine with mixed results. This paper reports an attempt at vaccination against EMCV using a genetically engineered, live attenuated Mengo virus (vMC0) at the Audubon Park Zoo and Miami Metro Zoo, (Miami, Florida, USA) from December 1996 to June 1997. Several species of animals were vaccinated with vMC0, which is serologically indistinguishable from the field strain of EMCV. Serum samples were taken at the time of vaccination and again 21 days later, then submitted for serum neutralization titers against EMCV. The vaccinate species included red capped mangebey (Cercocebus torquatus), colobus (Colobus guereza), angolan colobus (Colobus angolensis), ruffed lemur (Lemur variegatus ruber and Lemur variegatus variegatus), back lemur (Lemur macaco), ring-tailed lemur (Lemur catta), siamang (Hylobates syndactylus), diana guenon (Cercopithicus diana), spider monkey (Ateles geoffroyi), common marmoset (Callithrix jacchus), talapoin monkey (Cercopithecus talapoin), Brazilian tapir (Tapirus terrestris), Baird's tapir (Tapirus bairdii), Malayan tapir (Tapirus indicus), dromedary camel (Camelus dromedarius), bactrian camel (Camelus bactrianus), gerenuk (Litocranius walleri), guanaco (Lama glama guanicoe), black duiker (Cephalophus niger), Vietnamese potbellied pig (Sus scrofa), babirusa (Babyrousa babyrussa), collard peccary (Tayass tajacu), and African crested porcupine (Hystrix africaeaustralis). The vaccine response was variable, with high virus neutralizing antibody titer responses in some primate species and mixed to poor responses for other species. No ill effects were seen with vaccination. PMID:10231768

  9. HIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions.

    PubMed

    Rubens, Muni; Ramamoorthy, Venkataraghavan; Saxena, Anshul; Shehadeh, Nancy; Appunni, Sandeep

    2015-01-01

    HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines. PMID:26579546

  10. HIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions

    PubMed Central

    Rubens, Muni; Ramamoorthy, Venkataraghavan; Saxena, Anshul; Shehadeh, Nancy; Appunni, Sandeep

    2015-01-01

    HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines. PMID:26579546

  11. Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction.

    PubMed

    Renukaradhya, Gourapura J; Meng, Xiang-Jin; Calvert, Jay G; Roof, Michael; Lager, Kelly M

    2015-08-01

    Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork

  12. Genetically Engineered Poxviruses for Recombinant Gene Expression, Vaccination, and Safety

    NASA Astrophysics Data System (ADS)

    Moss, Bernard

    1996-10-01

    Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure--function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.

  13. [Vaccination perspectives].

    PubMed

    Saliou, P; Plotkin, S

    1994-01-01

    The aim of vaccinology is to improve the available vaccines and to develop new ones in the light of progress in immunology, molecular biology and biotechnologies. But it must go beyond this, and aim to protect all populations and control diseases, even eradicate them where possible. New vaccine strategies must be developed taking into account the epidemiology of diseases and the inherent logistic problems of implementing these strategies under local conditions. There are three major thrusts to the progress of the discipline. The improvement of the vaccines available. One of the drives of vaccinology is not only to deliver vaccines of increasing safety (replacement of the current vaccine for whooping cough with an acellular vaccine for example), but also to improve vaccine efficacy and immunogenicity (in particular for flu, tuberculosis, cholera and rabies vaccines). The optimisation of vaccination programmes and strategies for vaccinations. The ideal is to protect against the greatest possible number of diseases with the smallest number of vaccinations. The development of combinations of vaccines is central to this goal. The objective for the year 2000 is a hexavalent vaccine DTPP Hib HB. The development of new vaccines. Classic techniques continue to be successfully used (inactivated hepatitis A vaccine; attenuated live vaccines for chicken pox and dengue fever; conjugated polyosidic bacterial vaccines for meningococci and Streptococcus pneumoniae). However, it will become possible to prepare vaccines against most transmissible diseases using genetic engineering techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921696

  14. Genetic characterisation of attenuated SAD rabies virus strains used for oral vaccination of wildlife.

    PubMed

    Geue, Lutz; Schares, Susann; Schnick, Christina; Kliemt, Jeannette; Beckert, Aline; Freuling, Conrad; Conraths, Franz J; Hoffmann, Bernd; Zanoni, Reto; Marston, Denise; McElhinney, Lorraine; Johnson, Nicholas; Fooks, Anthony R; Tordo, Noel; Müller, Thomas

    2008-06-19

    The elimination of rabies from the red fox (Vulpes vulpes) in Western Europe has been achieved by the oral rabies vaccination (ORV) of wildlife with a range of attenuated rabies virus strains. With the exception of the vaccinia rabies glycoprotein recombinant vaccine (VRG), all strains were originally derived from a common ancestor; the Street Alabama Dufferin (SAD) field strain. However, after more than 30 years of ORV it is still not possible to distinguish these vaccine strains and there is little information on the genetic basis for their attenuation. We therefore sequenced and compared the full-length genome of five commercially available SAD vaccine viruses (SAD B19, SAD P5/88, SAG2, SAD VA1 and SAD Bern) and four other SAD strains (the original SAD Bern, SAD VA1, ERA and SAD 1-3670 Wistar). Nucleotide sequencing allowed identifying each vaccine strain unambiguously. Phylogenetic analysis revealed that the majority of the currently used commercial attenuated rabies virus vaccines appear to be derived from SAD B19 rather than from SAD Bern. One commercially available vaccine virus did not contain the SAD strain mentioned in the product information of the producer. Two SAD vaccine strains appeared to consist of mixed genomic sequences. Furthermore, in-del events targeting A-rich sequences (in positive strand) within the 3' non-coding regions of M and G genes were observed in SAD-derivates developed in Europe. Our data also supports the idea of a possible recombination that had occurred during the derivation of the European branch of SAD viruses. If confirmed, this recombination event would be the first one reported among RABV vaccine strains. PMID:18485548

  15. Optimal vaccination schedule search using genetic algorithm over MPI technology

    PubMed Central

    2012-01-01

    Background Immunological strategies that achieve the prevention of tumor growth are based on the presumption that the immune system, if triggered before tumor onset, could be able to defend from specific cancers. In supporting this assertion, in the last decade active immunization approaches prevented some virus-related cancers in humans. An immunopreventive cell vaccine for the non-virus-related human breast cancer has been recently developed. This vaccine, called Triplex, targets the HER-2-neu oncogene in HER-2/neu transgenic mice and has shown to almost completely prevent HER-2/neu-driven mammary carcinogenesis when administered with an intensive and life-long schedule. Methods To better understand the preventive efficacy of the Triplex vaccine in reduced schedules we employed a computational approach. The computer model developed allowed us to test in silico specific vaccination schedules in the quest for optimality. Specifically here we present a parallel genetic algorithm able to suggest optimal vaccination schedule. Results & Conclusions The enormous complexity of combinatorial space to be explored makes this approach the only possible one. The suggested schedule was then tested in vivo, giving good results. Finally, biologically relevant outcomes of optimization are presented. PMID:23148787

  16. Vaccinations in paediatric rheumatology: an update on current developments.

    PubMed

    Groot, Noortje; Heijstek, Marloes W; Wulffraat, Nico M

    2015-07-01

    In 2011, the European League Against Rheumatism (EULAR) published recommendations regarding the vaccination of children with rheumatic diseases. These recommendations were based on a systematic literature review published in that same year. Since then, the evidence body on this topic has grown substantially. This review provides an update of the systematic literature study of 2011, summarizing all the available evidence on the safety and immunogenicity of vaccination in paediatric patients with rheumatic diseases. The current search yielded 21 articles, in addition to the 27 articles described in the 2011 review. In general, vaccines are immunogenic and safe in this patient population. The effect of immunosuppressive drugs on the immunogenicity of vaccines was not detrimental for glucocorticosteroids and methotrexate. Biologicals could accelerate a waning of antibody levels over time, although most patients were initially protected adequately. Overall, persistence of immunological memory may be reduced in children with rheumatic diseases, which shows the need for (booster) vaccination. This update of the 2011 systematic literature review strengthens the evidence base for the EULAR recommendations, and it must be concluded that vaccinations in patients with rheumatic diseases should be advocated. PMID:26025339

  17. Ebola hemorrhagic Fever and the current state of vaccine development.

    PubMed

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

    2014-12-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine. PMID:25562048

  18. Ebola Hemorrhagic Fever and the Current State of Vaccine Development

    PubMed Central

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-il

    2014-01-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine. PMID:25562048

  19. Shigella vaccine development: prospective animal models and current status.

    PubMed

    Kim, Yeon-Jeong; Yeo, Sang-Gu; Park, Jae-Hak; Ko, Hyun-Jeong

    2013-01-01

    Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines. Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity. The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal models currently available, including the newly developed mouse model. PMID:24372251

  20. Current and Emerging Cell Culture Manufacturing Technologies for Influenza Vaccines

    PubMed Central

    Milián, Ernest; Kamen, Amine A.

    2015-01-01

    Annually, influenza virus infects millions of people worldwide. Vaccination programs against seasonal influenza infections require the production of hundreds of million doses within a very short period of time. The influenza vaccine is currently produced using a technology developed in the 1940s that relies on replicating the virus in embryonated hens' eggs. The monovalent viral preparation is inactivated and purified before being formulated in trivalent or tetravalent influenza vaccines. The production process has depended on a continuous supply of eggs. In the case of pandemic outbreaks, this mode of production might be problematic because of a possible drastic reduction in the egg supply and the low flexibility of the manufacturing process resulting in a lack of supply of the required vaccine doses in a timely fashion. Novel production systems using mammalian or insect cell cultures have emerged to overcome the limitations of the egg-based production system. These industrially well-established production systems have been primarily selected for a faster and more flexible response to pandemic threats. Here, we review the most important cell culture manufacturing processes that have been developed in recent years for mass production of influenza vaccines. PMID:25815321

  1. Current and emerging cell culture manufacturing technologies for influenza vaccines.

    PubMed

    Milián, Ernest; Kamen, Amine A

    2015-01-01

    Annually, influenza virus infects millions of people worldwide. Vaccination programs against seasonal influenza infections require the production of hundreds of million doses within a very short period of time. The influenza vaccine is currently produced using a technology developed in the 1940s that relies on replicating the virus in embryonated hens' eggs. The monovalent viral preparation is inactivated and purified before being formulated in trivalent or tetravalent influenza vaccines. The production process has depended on a continuous supply of eggs. In the case of pandemic outbreaks, this mode of production might be problematic because of a possible drastic reduction in the egg supply and the low flexibility of the manufacturing process resulting in a lack of supply of the required vaccine doses in a timely fashion. Novel production systems using mammalian or insect cell cultures have emerged to overcome the limitations of the egg-based production system. These industrially well-established production systems have been primarily selected for a faster and more flexible response to pandemic threats. Here, we review the most important cell culture manufacturing processes that have been developed in recent years for mass production of influenza vaccines. PMID:25815321

  2. Genetic Imprint of Vaccination on Simian/Human Immunodeficiency Virus Type 1 Transmitted Viral Genomes in Rhesus Macaques

    PubMed Central

    Varela, Mariana; Verschoor, Ernst; Lai, Rachel P. J.; Hughes, Joseph; Mooj, Petra; McKinley, Trevelyan J.; Fitzmaurice, Timothy J.; Landskron, Lisa; Willett, Brian J.; Frost, Simon D. W.; Bogers, Willy M.; Heeney, Jonathan L.

    2013-01-01

    Understanding the genetic, antigenic and structural changes that occur during HIV-1 infection in response to pre-existing immunity will facilitate current efforts to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the population level but little with regard to specific changes occurring in the envelope glycoprotein within a host in response to immune pressure elicited by antibodies. The aim of this study was to track and map specific early genetic changes occurring in the viral envelope gene following vaccination using a highly controlled viral challenge setting in the SHIV macaque model. We generated 449 full-length env sequences from vaccinees, and 63 from the virus inoculum. Analysis revealed a different pattern in the distribution and frequency of mutations in the regions of the envelope gene targeted by the vaccine as well as different patterns of diversification between animals in the naïve control group and vaccinees. Given the high stringency of the model it is remarkable that we were able to identify genetic changes associated with the vaccination. This work provides insight into the characterization of breakthrough viral populations in less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV challenge model in macaques to unravel the mechanisms driving HIV-1 envelope genetic diversity in the presence of vaccine induced-responses. PMID:23967111

  3. From The Cover: Poly- amino ester-containing microparticles enhance the activity of nonviral genetic vaccines

    NASA Astrophysics Data System (ADS)

    Little, Steven R.; Lynn, David M.; Ge, Qing; Anderson, Daniel G.; Puram, Sidharth V.; Chen, Jianzhu; Eisen, Herman N.; Langer, Robert

    2004-06-01

    Current nonviral genetic vaccine systems are less effective than viral vaccines, particularly in cancer systems where epitopes can be weakly immunogenic and antigen-presenting cell processing and presentation to T cells is down-regulated. A promising nonviral delivery method for genetic vaccines involves microencapsulation of antigen-encoding DNA, because such particles protect plasmid payloads and target them to phagocytic antigen-presenting cells. However, conventional microparticle formulations composed of poly lactic-co-glycolic acid take too long to release encapsulated payload and fail to induce high levels of target gene expression. Here, we describe a microparticle-based DNA delivery system composed of a degradable, pH-sensitive poly- amino ester and poly lactic-co-glycolic acid. These formulations generate an increase of 3-5 orders of magnitude in transfection efficiency and are potent activators of dendritic cells in vitro. When used as vaccines in vivo, these microparticle formulations, unlike conventional formulations, induce antigen-specific rejection of transplanted syngenic tumor cells.

  4. Ocean currents help explain population genetic structure

    PubMed Central

    White, Crow; Selkoe, Kimberly A.; Watson, James; Siegel, David A.; Zacherl, Danielle C.; Toonen, Robert J.

    2010-01-01

    Management and conservation can be greatly informed by considering explicitly how environmental factors influence population genetic structure. Using simulated larval dispersal estimates based on ocean current observations, we demonstrate how explicit consideration of frequency of exchange of larvae among sites via ocean advection can fundamentally change the interpretation of empirical population genetic structuring as compared with conventional spatial genetic analyses. Both frequency of larval exchange and empirical genetic difference were uncorrelated with Euclidean distance between sites. When transformed into relative oceanographic distances and integrated into a genetic isolation-by-distance framework, however, the frequency of larval exchange explained nearly 50 per cent of the variance in empirical genetic differences among sites over scales of tens of kilometres. Explanatory power was strongest when we considered effects of multiple generations of larval dispersal via intermediary locations on the long-term probability of exchange between sites. Our results uncover meaningful spatial patterning to population genetic structuring that corresponds with ocean circulation. This study advances our ability to interpret population structure from complex genetic data characteristic of high gene flow species, validates recent advances in oceanographic approaches for assessing larval dispersal and represents a novel approach to characterize population connectivity at small spatial scales germane to conservation and fisheries management. PMID:20133354

  5. Capripox disease in Ethiopia: Genetic differences between field isolates and vaccine strain, and implications for vaccination failure.

    PubMed

    Gelaye, Esayas; Belay, Alebachew; Ayelet, Gelagay; Jenberie, Shiferaw; Yami, Martha; Loitsch, Angelika; Tuppurainen, Eeva; Grabherr, Reingard; Diallo, Adama; Lamien, Charles Euloge

    2015-07-01

    Sheeppox virus (SPPV), goatpox virus (GTPV) and lumpy skin disease virus (LSDV) of the genus Capripoxvirus (CaPV) cause capripox disease in sheep, goats and cattle, respectively. These viruses are not strictly host-specific and their geographical distribution is complex. In Ethiopia, where sheep, goats and cattle are all affected, a live attenuated vaccine strain (KS1-O180) is used for immunization of both small ruminants and cattle. Although occurrences of the disease in vaccinated cattle are frequently reported, information on the circulating isolates and their relation to the vaccine strain in use are still missing. The present study addressed the parameters associated with vaccination failure in Ethiopia. Retrospective outbreak data were compiled and isolates collected from thirteen outbreaks in small ruminants and cattle at various geographical locations and years were analyzed and compared to the vaccine strain. Isolates of GTPV and LSDV genotypes were responsible for the capripox outbreaks in small ruminants and cattle, respectively, while SPPV was absent. Pathogenic isolates collected from vaccinated cattle were identical to those from the non-vaccinated ones. The vaccine strain, genetically distinct from the outbreak isolates, was not responsible for these outbreaks. This study shows capripox to be highly significant in Ethiopia due to low performance of the local vaccine and insufficient vaccination coverage. The development of new, more efficient vaccine strains, a GTPV strain for small ruminants and a LSDV for cattle, is needed to promote the acceptance by farmers, thus contribute to better control of CaPVs in Ethiopia. PMID:25907637

  6. Synthetic DNA Vaccines: Improved Vaccine Potency by Electroporation and Co-Delivered Genetic Adjuvants

    PubMed Central

    Flingai, Seleeke; Czerwonko, Matias; Goodman, Jonathan; Kudchodkar, Sagar B.; Muthumani, Kar; Weiner, David B.

    2013-01-01

    In recent years, DNA vaccines have undergone a number of technological advancements that have incited renewed interest and heightened promise in the field. Two such improvements are the use of genetically engineered cytokine adjuvants and plasmid delivery via in vivo electroporation (EP), the latter of which has been shown to increase antigen delivery by nearly 1000-fold compared to naked DNA plasmid delivery alone. Both strategies, either separately or in combination, have been shown to augment cellular and humoral immune responses in not only mice, but also in large animal models. These promising results, coupled with recent clinical trials that have shown enhanced immune responses in humans, highlight the bright prospects for DNA vaccines to address many human diseases. PMID:24204366

  7. Vaccines against Gonorrhea: Current status and Future Challenges

    PubMed Central

    Jerse, Ann E.; Bash, Margaret C.; Russell, Michael W.

    2013-01-01

    Gonorrhea occurs at high incidence throughout the world and significantly impacts reproductive health and the spread of human immunodeficiency virus. Current control measures are inadequate and seriously threatened by the rapid emergence of antibiotic resistance. Progress on gonorrhea vaccines has been slow; however, recent advances justify significant effort in this area. Conserved vaccine antigens have been identified that elicit bactericidal antibodies and, or play key roles in pathogenesis that could be targeted by a vaccine-induced response. A murine genital tract infection model is available for systematic testing of antigens, immunization routes and adjuvants, and transgenic mice exist to relieve some host restrictions. Furthermore, mechanisms by which N. gonorrhoeae avoids inducing a protective adaptive response are being elucidated using human cells and the mouse model. Induction of a Th1 response in mice clears infection and induces a memory response, which suggests Th1-inducing adjuvants may be key in vaccine-induced protection. Continued research in this area should include human testing and clinical studies to confirm or negate findings from experimental systems and to define protective host factors. PMID:24016806

  8. Live attenuated vaccines: Historical successes and current challenges

    SciTech Connect

    Minor, Philip D.

    2015-05-15

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.

  9. Circulating vaccine-derived polioviruses: current state of knowledge.

    PubMed Central

    Kew, Olen M.; Wright, Peter F.; Agol, Vadim I.; Delpeyroux, Francis; Shimizu, Hiroyuki; Nathanson, Neal; Pallansch, Mark A.

    2004-01-01

    Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence. PMID:15106296

  10. [Genetics of depression. Current knowledge and perspectives].

    PubMed

    Maier, W

    2004-05-01

    Depression is a common disorder (lifetime prevalence nearly 20% in industrialized countries) that presents in two etiologically different forms (unipolar depression, bipolar disorder). Both forms are subject to a genetic influence, which is stronger in bipolar disorder. Unipolar depression is also strongly influenced by nongenetic environmental factors (e. g., traumas, socialization, critical life events). There is strong evidence for a gene-- environmental interaction in unipolar depression. The search for genes was recently very successful in bipolar disorder. There is currently no evidence for disposition genes with strong effects. The prediction of response to selective serotonin-reuptake inhibitors (SSRI) by genetic markers presents currently the best confirmed molecular-genetic findings for unipolar depression. Complicating factors are gene--environmental interaction, only small to modest effects of disposition genes, and putative epigenetic mechanisms. PMID:15205762

  11. [VACCINES].

    PubMed

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs. PMID:26685562

  12. Current Knowledge on Genetic Biofortification in Lentil.

    PubMed

    Kumar, Jitendra; Gupta, Debjyoti Sen; Kumar, Shiv; Gupta, Sanjeev; Singh, Narendra Pratap

    2016-08-24

    Micronutrient deficiency in the human body, popularly known as "hidden hunger", causes many health problems. It presently affects >2 billion people worldwide, especially in South Asia and sub-Saharan Africa. Biofortification of food crop varieties is one way to combat the problem of hidden hunger using conventional plant breeding and transgenic methods. Lentils are rich sources of protein, micronutrients, and vitamins including iron, zinc, selenium, folates, and carotenoids. Lentil genetic resources including germplasm and wild species showed genetic variability for these traits. Studies revealed that a single serving of lentils could provide a significant amount of the recommended daily allowance of micronutrients and vitamins for adults. Therefore, lentils have been identified as a food legume for biofortification, which could provide a whole food solution to the global micronutrient malnutrition. The present review discusses the current ongoing efforts toward genetic biofortification in lentils using classical breeding and molecular marker-assisted approaches. PMID:27507630

  13. Nontyphoidal salmonella disease: Current status of vaccine research and development.

    PubMed

    Tennant, Sharon M; MacLennan, Calman A; Simon, Raphael; Martin, Laura B; Khan, M Imran

    2016-06-01

    Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally. The global incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases, approximately 80 million of which were contracted via food-borne transmission. It is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children. Symptoms of iNTS are similar to malaria, often including fever (>90%) and splenomegaly (>40%). The underlying reasons for the high rates of iNTS disease in Africa are still being elucidated. Evidence from animal and human studies supports the feasibility of developing a safe and effective vaccine against iNTS. Both antibodies and complement can kill Salmonella species in vitro. Proof-of-principle studies in animal models have demonstrated efficacy for live attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of serovars Typhimurium and Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been developed: the Generalized Modules for Membrane Antigens (GMMA) technology which presents surface polysaccharides and outer membrane proteins in their native conformation. GMMA technology is self-adjuvanting, as it delivers multiple pathogen-associated molecular pattern molecules. GMMA may be particularly relevant for low- and middle-income countries as it has the potential for high immunologic potency at a low cost and involves a relatively simple production process without the need for complex conjugation. Several vaccines for the predominant NTS serovars Typhimurium and Enteritidis, are

  14. How can plant genetic engineering contribute to cost-effective fish vaccine development for promoting sustainable aquaculture?

    PubMed

    Clarke, Jihong Liu; Waheed, Mohammad Tahir; Lössl, Andreas G; Martinussen, Inger; Daniell, Henry

    2013-09-01

    Aquaculture, the fastest growing food-producing sector, now accounts for nearly 50 % of the world's food fish (FAO in The state of world fisheries and aquaculture. FAO, Rome, 2010). The global aquaculture production of food fish reached 62.7 million tonnes in 2011 and is continuously increasing with an estimated production of food fish of 66.5 million tonnes in 2012 (a 9.4 % increase in 1 year, FAO, www.fao.org/fishery/topic/16140 ). Aquaculture is not only important for sustainable protein-based food fish production but also for the aquaculture industry and economy worldwide. Disease prevention is the key issue to maintain a sustainable development of aquaculture. Widespread use of antibiotics in aquaculture has led to the development of antibiotic-resistant bacteria and the accumulation of antibiotics in the environment, resulting in water and soil pollution. Thus, vaccination is the most effective and environmentally-friendly approach to combat diseases in aquaculture to manage fish health. Furthermore, when compared to >760 vaccines against human diseases, there are only about 30 fish vaccines commercially available, suggesting the urgent need for development and cost-effective production of fish vaccines for managing fish health, especially in the fast growing fish farming in Asia where profit is minimal and therefore given high priority. Plant genetic engineering has made significant contributions to production of biotech crops for food, feed, valuable recombinant proteins etc. in the past three decades. The use of plants for vaccine production offers several advantages such as low cost, safety and easy scaling up. To date a large number of plant-derived vaccines, antibodies and therapeutic proteins have been produced for human health, of which a few have been made commercially available. However, the development of animal vaccines in plants, especially fish vaccines by genetic engineering, has not yet been addressed. Therefore, there is a need to exploit

  15. DNA vaccination of poultry: The current status in 2015.

    PubMed

    Meunier, Marine; Chemaly, Marianne; Dory, Daniel

    2016-01-01

    DNA vaccination is a promising alternative strategy for developing new human and animal vaccines. The massive efforts made these past 25 years to increase the immunizing potential of this kind of vaccine are still ongoing. A relatively small number of studies concerning poultry have been published. Even though there is a need for new poultry vaccines, five parameters must nevertheless be taken into account for their development: the vaccine has to be very effective, safe, inexpensive, suitable for mass vaccination and able to induce immune responses in the presence of maternal antibodies (when appropriate). DNA vaccination should meet these requirements. This review describes studies in this field performed exclusively on birds (chickens, ducks and turkeys). No evaluations of avian DNA vaccine efficacy performed on mice as preliminary tests have been taken into consideration. The review first describes the state of the art for DNA vaccination in poultry: pathogens targeted, plasmids used and different routes of vaccine administration. Second, it presents strategies designed to improve DNA vaccine efficacy: influence of the route of administration, plasmid dose and age of birds on their first inoculation; increasing plasmid uptake by host cells; addition of immunomodulators; optimization of plasmid backbones and codon usage; association of vaccine antigens and finally, heterologous prime-boost regimens. The final part will indicate additional properties of DNA vaccines in poultry: fate of the plasmids upon inoculation, immunological considerations and the use of DNA vaccines for purposes other than preventing infectious diseases. PMID:26620840

  16. Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea.

    PubMed

    Zhang, Weiping; Sack, David A

    2015-09-01

    Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development. PMID:26135975

  17. Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea

    PubMed Central

    Sack, David A.

    2015-01-01

    Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development. PMID:26135975

  18. Vaccination as part of an AI control strategy -- currently available tools for emergency vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interest in vaccination for avian influenza virus is growing because of the perceived value vaccination has to offer. Vaccination can either be used for disease control or as part of an eradication strategy. Proper vaccination will not only prevent clinical disease, but it will also reduce virus s...

  19. Current developments for improving efficacy of allergy vaccines.

    PubMed

    Sandrini, Alessandra; Rolland, Jennifer M; O'Hehir, Robyn E

    2015-01-01

    Allergic diseases are prevalent worldwide. Allergen immunotherapy (AIT) is a current treatment for allergy, leading to modification of the natural course of disease. Mechanisms of efficacy include Treg through release of IL-10 and TGF-β and specific IgG4 blocking antibodies. Subcutaneous and sublingual routes are popular, but uptake is limited by inconvenience and safety concerns. Inclusion criteria limit application to a small proportion of allergic patients. New forms of immunotherapy are being investigated for more efficacious, convenient and safer options with promising advances in recent years. The rationale of reducing vaccine allergenicity to increase safety while improving immunogenicity led to investigation of T-cell epitope-based peptides and recombinant allergen derivatives. Additionally, different routes of administration and adjuvants and adjunct therapies are being explored. This review discusses the current status of AIT and recent advances to improve clinical efficacy, safety and long-term immune tolerance. PMID:26013124

  20. The Current State of Vaccine Development for Ocular HSV-1 Infection

    PubMed Central

    Royer, DJ; Cohen, A; Carr, DJJ

    2015-01-01

    Summary HSV-1 continues to be the leading cause of infectious corneal blindness. Clinical trials for vaccines against genital HSV infection have been ongoing for more than three decades. Despite this, no approved vaccine exists, and no formal clinical trials have evaluated the impact of HSV vaccines on eye health. We review here the current state of development for an efficacious HSV-1 vaccine and call for involvement of ophthalmologists and vision researchers. PMID:25983856

  1. Assessment of inactivated human rabies vaccines: biochemical characterization and genetic identification of virus strains.

    PubMed

    Finke, Stefan; Karger, Axel; Freuling, Conrad; Müller, Thomas

    2012-05-21

    The World Health Organization (WHO) recommends the periodic evaluation of the purity of the cell lines used in the production of rabies vaccines, as well as the antigenic identity of the virus strains. Here, we analyzed seventeen marketed inactivated human rabies virus vaccines for viral and non-viral proteins by SDS-PAGE and Coomassie/silver staining. Mass spectrometric analysis of an abundant 60-70 kDa signal indicated that in most vaccines serum albumin of human origin (HSA) was the major component. Quantification of HSA in the vaccines revealed a mean concentration of 22 mg HSA/dose in all tested PVRV (purified vero cell rabies vaccine), HDCV (human diploid cell rabies vaccine) and PHK (primary hamster kidney) vaccines. In contrast, 1000-fold lower HSA levels and no HSA were detected in PCECV (purified chick embryo cell-culture vaccine) and PDEV (duck embryo rabies vaccine), respectively. Western blot analyses further confirmed a high bias in the HSA content, whereas the virus protein levels were rather similar in all tested vaccines. In addition, the vaccine viruses were sequenced within the N- and G-genes to identify the strain. In the majority of sequenced vaccines, the declared vaccine strain was confirmed. However, some discrepancies in the genetic identification were observed, supporting WHO's recommendation for the molecular characterization of vaccine seed strains. This research highlights the variation in purity found between different human rabies virus vaccines, and suggests that further research is needed to establish the impact non-active components have on the potency of such vaccines. PMID:22469862

  2. Genetic testing for melanoma predisposition: current challenges.

    PubMed

    Gerstenblith, Meg R; Goldstein, Alisa M; Tucker, Margaret A; Fraser, Mary C

    2007-01-01

    A complex interaction of genetic, host, and environmental factors results in cutaneous malignant melanoma, the fifth most common cancer among men and the sixth among women in the United States. Mortality rates for cutaneous malignant melanoma depend on stage at diagnosis; thus, efforts are aimed at early detection and identification of risk factors for melanoma to distinguish those individuals requiring close surveillance. Melanoma susceptibility genes CDKN2A and CDK4 play a role in the development of melanoma, especially among some familial melanoma kindreds. The functions of CDKN2A and CDK4 in melanoma development, however, are currently incompletely understood. Therefore, at this time, predictive genetic testing for CDKN2A mutations outside of defined research protocols is not recommended because of the low likelihood of detecting mutations even in high-risk groups, the present inadequacy of interpreting a test result due to variations in penetrance and unclear associations with other cancers, and the minimal influence knowledge of mutation status currently has on medical management. Oncology nurses have an important role in identifying individuals at high risk for melanoma regardless of CDKN2A mutation status, encouraging enrollment in skin surveillance programs, and providing patient education regarding sun protection, prevention and early detection of melanoma. PMID:18025917

  3. In vivo and in vitro genetic recombination between conventional and gene-deleted vaccine strains of pseudorabies virus.

    PubMed

    Henderson, L M; Katz, J B; Erickson, G A; Mayfield, J E

    1990-10-01

    Pseudorabies virus (PRV), an alpha-herpesvirus, causes substantial economic losses in the swine industry and is currently the focus of eradication and control programs. Some of these programs rely on the ability of veterinarians to differentiate animals exposed to virulent strains of PRV from animals exposed to avirulent vaccine strains of PRV on the basis of a serologic response to nonessential glycoproteins that are deleted in some vaccine strains of PRV. Genetic recombination resulting in the creation of virulent strains of PRV with the same negative immunologic markers as vaccine strains could disrupt these programs. Two strains of PRV were coinoculated either into tissue culture or into sheep to facilitate recombination. Progeny viruses were selected to detect a specific recombinant phenotype. We were able to detect genetic recombination between vaccine strains of PRV following in vitro or in vivo coinoculation of 2 strains of PRV. The selected recombinants had marker-deleted phenotypes in strains with restored virulence genes. Increased virulence was observed in sheep after coinoculation of 2 avirulent vaccine strains of PRV. PMID:2173449

  4. Current Trends in West Nile Virus Vaccine Development

    PubMed Central

    Amanna, Ian J.; Slifka, Mark K.

    2014-01-01

    West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999-2012, there have been 37,088 reported cases of WNV and 1,549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been 8 clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost-effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged. PMID:24689659

  5. [Biotechnology and vaccinations].

    PubMed

    Peret, R

    1990-12-01

    Current biotechnologies used in the manufacture of new vaccines are of three kinds: Genetic recombinations leading to either vaccinal sub-units or living vaccines represented by recombinant vectors; Chemical synthesis techniques; Use of the spatial configuration of an anti-antibody similar to the initial antigen. These are the anti-idiotype vaccines. Genetic engineering is the basis of a new generation of vaccines, sought with the aim of attempting to eradicate a number of diseases throughout the world. However, there is presently an inadequacy in resources, most often linked to financial considerations, which limits widespread systematic vaccination. In the future, vaccines against dental caries will probably be obtained from purified proteins of hydrolase fractions common to cariogenic bacteria and resulting from genetic recombinations in the form of vaccinal sub-units. PMID:2077866

  6. Public vaccine manufacturing capacity in the Latin American and Caribbean region: current status and perspectives.

    PubMed

    Cortes, Maria de los Angeles; Cardoso, Daniel; Fitzgerald, James; DiFabio, Jose Luis

    2012-01-01

    The vaccine global market is currently growing at a rate of 16.52%. Nowadays the vaccine manufacturing industry is limited in the sense that not all vaccine manufacturers have the capacity to execute all the steps necessary to produce a successful product. The biological variation inherent to vaccine manufacturing and the initial investment required to bring a vaccine to the market are some of the factors that discourage vaccine manufacturing initiatives. Given the current global context in vaccine innovation and production, and the increasing participation of vaccine manufacturers from developing countries in global markets, this paper aims to review vaccine manufacturing capacity in Latin American and Caribbean (LAC) countries with specific focus on trends in national or public sector manufacturing, presenting current challenges and future opportunities for the sector in meeting national and regional (LAC) needs. Despite the overall low vaccine manufacturing capacity reported within the LAC region within this paper, it is considered that the relatively high and concentrated capacity that exists within a number of countries, combined with political commitment of all countries within the Region, can provide the necessary platform for the continued development of capacity in vaccine development and manufacture within LAC. PMID:22033155

  7. Current developments in avian influenza vaccines including food safety aspects in vaccinated birds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Historically, vaccines against avian influenza (AI) have had more limited use in poultry than vaccines for other poultry diseases such as Newcastle disease (ND) and infectious bronchitis. These AI vaccines have been primarily based on low or high pathogenicity (HP) AI viruses that were grown in emb...

  8. Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

    PubMed Central

    Wolfe, Daniel N.; Heppner, D. Gray; Gardner, Shea N.; Jaing, Crystal; Dupuy, Lesley C.; Schmaljohn, Connie S.; Carlton, Kevin

    2014-01-01

    Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure. PMID:24842880

  9. Prophylactic vaccinations in chronic kidney disease: Current status

    PubMed Central

    Grzegorzewska, Alicja E

    2015-01-01

    In this review, recent data on results concerning prophylactic vaccinations against hepatitis B virus, influenza viruses, and pneumococci are presented. Effects of active immunization in chronic kidney disease depend on category of glomerular filtration rate (GFR). The lower GFR category the better results of response to vaccination. Abnormalities in toll-like receptors and down-regulation of B-cell activating factor receptor in transitional B cells were recently included into uremia-associated deficits in immunocompetence. Development of novel, more potent vaccines containing toll-like receptor agonists as adjuvants may help to achieve more effective immunization against hepatitis B virus in immunocompromised patients. Experimental studies announce further vaccine adjuvants. A vaccine against hepatitis C virus is not available yet, but promising results were already obtained in the experimental and preliminary clinical studies. Prophylactic vaccinations against influenza viruses and pneumococci become increasingly popular in dialysis facilities due to their proved benefits. PMID:25911956

  10. Therapeutic vaccination to treat chronic infectious diseases: current clinical developments using MVA-based vaccines.

    PubMed

    Boukhebza, Houda; Bellon, Nadine; Limacher, Jean Marc; Inchauspé, Geneviève

    2012-12-01

    A famous milestone in the vaccine field has been the first successful vaccination against smallpox, in 1798, by Edward Jenner. Using the vaccinia cowpox virus, Jenner was able to protect vaccinees from variola or smallpox. The Modified Virus Ankara (MVA) poxvirus strain has been one of the vaccines subsequently developed to prevent smallpox infection and was selected by the US government in their Biodefense strategy. Progress in molecular biology and immunology associated with MVA infection has led to the development of MVA as vaccine platform, both in the field of preventive and therapeutic vaccines. This later class of therapeutics has witnessed growing interest that has translated into an increasing number of vaccine candidates reaching the clinics. Among those, MVA-based therapeutic vaccines have addressed four major chronic infections including viral hepatitis, AIDS, human papillomavirus-linked pathologies and tuberculosis. Clinical trials encompass phase 1 and 2 and have started to show significant results and promises. PMID:22894957

  11. TB vaccine development and the End TB Strategy: importance and current status

    PubMed Central

    Fletcher, Helen A.; Schrager, Lewis

    2016-01-01

    TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some of the key strategies being embraced by the field to overcome these challenges. Currently, 8 of the 13 vaccines in clinical development are subunit vaccines; 6 of these contain or express either Ag85A or Ag85B proteins. A major challenge to TB vaccine development is the lack of diversity in both the antigens included in TB vaccines, and the immune responses elicited by TB vaccine candidates. Both will need to be expanded to maximise the potential for developing a successful candidate by 2025. Current research efforts are focused on broadening both antigen selection and the range of vaccine-mediated immune responses. Previous and ongoing TB vaccine efficacy trials have built capacity, generated high quality data on TB incidence and prevalence, and provided insight into immune correlates of risk of TB disease. These gains will enable the design of better TB vaccines and, importantly, move these vaccines into efficacy trials more rapidly and at a lower cost than was possible for previous TB vaccine candidates. PMID:27076508

  12. TB vaccine development and the End TB Strategy: importance and current status.

    PubMed

    Fletcher, Helen A; Schrager, Lewis

    2016-04-01

    TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some of the key strategies being embraced by the field to overcome these challenges. Currently, 8 of the 13 vaccines in clinical development are subunit vaccines; 6 of these contain or express either Ag85A or Ag85B proteins. A major challenge to TB vaccine development is the lack of diversity in both the antigens included in TB vaccines, and the immune responses elicited by TB vaccine candidates. Both will need to be expanded to maximise the potential for developing a successful candidate by 2025. Current research efforts are focused on broadening both antigen selection and the range of vaccine-mediated immune responses. Previous and ongoing TB vaccine efficacy trials have built capacity, generated high quality data on TB incidence and prevalence, and provided insight into immune correlates of risk of TB disease. These gains will enable the design of better TB vaccines and, importantly, move these vaccines into efficacy trials more rapidly and at a lower cost than was possible for previous TB vaccine candidates. PMID:27076508

  13. Vaccine adjuvants - Current status and prospects on controlled release adjuvancity.

    PubMed

    Sivakumar, S M; Safhi, Mohammed M; Kannadasan, M; Sukumaran, N

    2011-10-01

    The strategy of World Health Organization is to develop efficient and inexpensive vaccine against various infectious diseases amongst children's population. Vaccination is considered as the most cost effective health intervention known to public. Since 90 years various substances have been added in vaccine formulation but still alum is considered as the safest adjuvant for human use licensed by United States Food and Drug Administration. MF 59 and ASO4 are the adjuvants were developed recently and approved for human use. Due to poor adjuvancity, conventional vaccines require multiple recall injection at approximately time intervals to attain optimal immune response. For past approximately two decades the vaccine research has been focused towards the alternation of alum type of adjuvant in order to increase the immunogenicity. The development of new vaccines, is more efficacious or easier to deliver, or both have become an area of research that can certainly benefit from controlled release technology. Especially, the conversion of multiple administration vaccine into single administration vaccine may represent an improved advancement towards the betterment of human health care and welfare. Biodegradable polymer microparticles have been evaluated for delivering antigens in native form, sustained release keeping in mind the safety aspects. In this article we review the overall concept of adjuvants in vaccine technology with special focus towards the prospects of controlled release antigens. PMID:23960760

  14. Adjuvants and delivery systems for antifungal vaccines: current state and future developments.

    PubMed

    Portuondo, Deivys Leandro F; Ferreira, Lucas S; Urbaczek, Ana C; Batista-Duharte, Alexander; Carlos, Iracilda Z

    2015-01-01

    Mycoses are gaining increasing attention in modern medicine because of the increase in diseases associated with opportunistic fungal infections. Despite the recognized role of the immune system in the control of fungal infections, no antifungal vaccines are currently licensed for use in humans. However, numerous vaccine candidates are being developed in many laboratories, as proof of the renewed interest in integrating or replacing chemotherapy with vaccines to reduce antibiotic use and consequently limit drug resistance and toxicity. In the effort to use safer and simpler fungal antigens for vaccinations, adjuvants have become relevant as immunostimulators to elicit successful protective immune responses. To address the relevant role of adjuvants as determinants in the balance of vaccine efficacy and safety, an updated and critical review of the adjuvants used in preclinical antifungal vaccines is presented, and prospective trends are addressed. Selected recent papers and other historically relevant and innovative strategies using adjuvants in experimental fungal vaccines are highlighted. PMID:25362733

  15. DNA vaccines and their applications in veterinary practice: current perspectives.

    PubMed

    Dhama, K; Mahendran, Mahesh; Gupta, P K; Rai, A

    2008-06-01

    Inoculation of plasmid DNA, encoding an immunogenic protein gene of an infectious agent, stands out as a novel approach for developing new generation vaccines for prevention of infectious diseases of animals. The potential of DNA vaccines to act in presence of maternal antibodies, its stability and cost effectiveness and the non-requirement of cold chain have heightened the prospects. Even though great strides have been made in nucleic acid vaccination, still there are many areas that need further research for its wholesome practical implementation. Major areas of concern are vaccine delivery, designing of suitable vectors and cytotoxic T cell responses. Also, the induction of immune responses by DNA vaccines is inconclusive due to the lack of knowledge regarding the concentration of the protein expressed in vivo. Alternative delivery systems having higher transfection efficiency and the use of cytokines, as immunomodulators, needs to be further explored. Recently, efforts are being made to modulate and prolong the active life of dendritic cells, in order to make antigen presentation a more efficacious one. For combating diseases like acquired immunodeficiency syndrome (AIDS), influenza, malaria and tuberculosis in humans; and foot and mouth disease, Aujesky's disease, swine fever, rabies, canine distemper and brucellosis in animals, DNA vaccine clinical trials are underway. This review highlights the salient features of DNA vaccines, and measures to enhance their efficacy so as to devise an effective and novel vaccination strategy against animal diseases. PMID:18425596

  16. Vaccines against invasive Salmonella disease: current status and future directions.

    PubMed

    MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

    2014-01-01

    Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

  17. Genetic stability of vaccine strains by multilocus sequence typing and pulsed-field gel electrophoresis analysis: Implications for quality control of the leptospiral vaccine

    PubMed Central

    Xu, Yinghua; Zhang, Jinlong; Cui, Shenghui; Li, Min; Zhang, Ying; Xue, Honggang; Xin, Xiaofang; Wang, Junzhi

    2015-01-01

    Quality control of vaccine strains is directly associated with the safety and efficacy of inactivated whole bacterial vaccines. The assessment of genetic stability is one of the essential elements to guarantee the quality of vaccine strains. The multiple-valence inactivated leptospiral vaccine, comprising the main circulating serogroups, has played an important role in the control of Leptospira infection in China. In the present study, to assess the genetic stability of vaccine strains and develop novel quality control tests that enhance and extend the existing procedures, 7 Chinese leptospiral vaccine strains were characterized during in vivo and in vitro passages by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) analysis. The seven vaccine strains were found to have distinct sequence types (STs) and PFGE profiles. Further analysis showed that the ST and PFGE pattern of each vaccine strain, after in vivo or serial in vitro passages (up to 20 passages), were identical to those of the initial strain, demonstrating that these strains were genetically stable and homogeneous. Taken together, PFGE and MLST provide a reproducible and reliable means for confirming the identity and genetic stability of vaccine seeds, suggesting that these approaches can be used to evaluate the quality of leptospiral vaccine strains. PMID:25806658

  18. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    PubMed Central

    2012-01-01

    Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus

  19. Current status of GV1001 and other telomerase vaccination strategies in the treatment of cancer.

    PubMed

    Shaw, V E; Naisbitt, D J; Costello, E; Greenhalf, W; Park, B K; Neoptolemos, J P; Middleton, G W

    2010-09-01

    GV1001 is a telomerase-specific, promiscuous class II peptide vaccine which is currently in an advanced stage of clinical development. This article reviews the biological rationale underpinning the design of ongoing studies with the vaccine as well as its immunogenicity and clinical activity. It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer. PMID:20822343

  20. Syndactyly: phenotypes, genetics and current classification

    PubMed Central

    Malik, Sajid

    2012-01-01

    Syndactyly is one of the most common hereditary limb malformations depicting the fusion of certain fingers and/or toes. It may occur as an isolated entity or a component of more than 300 syndromic anomalies. Syndactylies exhibit great inter- and intra-familial clinical variability. Even within a subject, phenotype can be unilateral or bilateral and symmetrical or asymmetrical. At least nine non-syndromic syndactylies with additional sub-types have been characterized. Most of the syndactyly types are inherited as autosomal dominant but two autosomal recessive and an X-linked recessive entity have also been described. Whereas the underlying genes/mutations for types II-1, III, IV, V, and VII have been worked out, the etiology and molecular basis of the other syndactyly types remain unknown. In this communication, based on an overview of well-characterized isolated syndactylies, their cardinal phenotypes, inheritance patterns, and clinical and genetic heterogeneities, a ‘current classification scheme' is presented. Despite considerable progress in the understanding of syndactyly at clinical and molecular levels, fundamental questions regarding the disturbed developmental mechanisms leading to fused digits, remain to be answered. PMID:22333904

  1. Immunogenicity and safety of currently available Japanese encephalitis vaccines: A systematic review

    PubMed Central

    Li, Xing; Ma, Shu-Juan; Liu, Xie; Jiang, Li-Na; Zhou, Jun-Hua; Xiong, Yi-Quan; Ding, Hong; Chen, Qing

    2015-01-01

    A number of Japanese encephalitis (JE) vaccines have been used for preventing Japanese encephalitis around the world. We here reviewed the immunogenicity and safety of the currently available Japanese encephalitis vaccines. We searched Pubmed, Embase, Web of Science, the Cochrane Library and other online databases up to March 25, 2014 for studies focusing on currently used JE vaccines in any language. The primary outcomes were the seroconversion rate against JEV and adverse events. Meta-analysis was performed for the primary outcome when available. A total of 51 articles were included. Studies were grouped on the basic types of vaccines. This systematic review led to 2 aspects of the conclusions. On one hand, all the currently available JE vaccines are safe and effective. On the other hand, the overall of JE vaccine evaluation is disorganized, the large variation in study designs, vaccine types, schedules, doses, population and few hand-to-hand trails, make direct comparisons difficult. In order to make a more evidence-based decision on optimizing the JE vaccine, it is warranted to standardize the JE vaccine evaluation research. PMID:25668666

  2. Current Role of Genetics in Hematologic Malignancies.

    PubMed

    Prakash, Gaurav; Kaur, Anupriya; Malhotra, Pankaj; Khadwal, Alka; Sharma, Prashant; Suri, Vikas; Varma, Neelam; Varma, Subhash

    2016-03-01

    Rapidly changing field of genetic technology and its application in the management of hematological malignancies has brought significant improvement in treatment and outcome of these disorders. Today, genetics plays pivotal role in diagnosis and prognostication of most hematologic neoplasms. The utilization of genetic tests in deciding specific treatment of various hematologic malignancies as well as for evaluation of depth of treatment response is rapidly advancing. Therefore, it is imperative for practitioners working in the field of hemato-oncology to have sufficient understanding of the basic concepts of genetics in order to comprehend upcoming molecular research in this area and to translate the same for patient care. PMID:26855503

  3. Current developments in avian influenza vaccines including food safety aspects in vaccinated birds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oil emulsified inactivated low or high pathogenicity (HP) avian influenza AI viruses were the only type of vaccines available for many years. More recently, recombinant fowl poxvirus and avian paramyxovirus type 1 vaccines with AI H5 gene inserts (+ or - N1 gene insert) have been licensed for use. ...

  4. [Vaccinations for travelers--a review of current recommendations].

    PubMed

    Katzir, Michal; Giladi, Michael

    2010-09-01

    The number of travelers abroad rises every year. Concurrently, the age and health conditions of the travelers are becoming increasingly varied as are their destinations and the degree of risk involved. In the face of this complexity, it is recommended that travelers seek medical advice at specializing travel medicine clinics before leaving for their trip. The object of the consultation is to fit the general guidelines regarding preventative behavior and vaccinations to the specific traveler. Several sources of information are available for receiving updated vaccination recommendations for travelers. Usually these sources provide similar recommendations but occasionally different instructions can be found. In this review, the authors discuss vaccination recommendations for travelers while pointing out the similarities and differences among the various information sources. The different recommendations for travelers groups and types are noted. The available vaccinations are reviewed, detailing the indications and contraindications as well as side effects. PMID:21302475

  5. Current perspective in tuberculosis vaccine development for high TB endemic regions.

    PubMed

    Husain, Aliabbas A; Daginawala, Hatim F; Singh, Lokendra; Kashyap, Rajpal S

    2016-05-01

    Tuberculosis (TB) continues to be a global epidemic, despite of the availability of Bacillus Calmette Guerin (BCG) vaccine for more than six decades. In an effort to eradicate TB, vaccinologist around the world have made considerable efforts to develop improved vaccine candidates, based on the understanding of BCG failure in developing world and immune response thought to be protective against TB. The present review represents a current perspective on TB vaccination research, including additional research strategies needed for increasing the efficacy of BCG, and for the development of new effective vaccines for high TB endemic regions. PMID:27156631

  6. Myeloproliferative neoplasms: Current molecular biology and genetics.

    PubMed

    Saeidi, Kolsoum

    2016-02-01

    Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by increased production of mature blood cells. Philadelphia chromosome-negative MPNs (Ph-MPNs) consist of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A number of stem cell derived mutations have been identified in the past 10 years. These findings showed that JAK2V617F, as a diagnostic marker involving JAK2 exon 14 with a high frequency, is the best molecular characterization of Ph-MPNs. Somatic mutations in an endoplasmic reticulum chaperone, named calreticulin (CALR), is the second most common mutation in patients with ET and PMF after JAK2 V617F mutation. Discovery of CALR mutations led to the increased molecular diagnostic of ET and PMF up to 90%. It has been shown that JAK2V617F is not the unique event in disease pathogenesis. Some other genes' location such as TET oncogene family member 2 (TET2), additional sex combs-like 1 (ASXL1), casitas B-lineage lymphoma proto-oncogene (CBL), isocitrate dehydrogenase 1/2 (IDH1/IDH2), IKAROS family zinc finger 1 (IKZF1), DNA methyltransferase 3A (DNMT3A), suppressor of cytokine signaling (SOCS), enhancer of zeste homolog 2 (EZH2), tumor protein p53 (TP53), runt-related transcription factor 1 (RUNX1) and high mobility group AT-hook 2 (HMGA2) have also identified to be involved in MPNs phenotypes. Here, current molecular biology and genetic mechanisms involved in MNPs with a focus on the aforementioned factors is presented. PMID:26697989

  7. Genetic detoxification of bacterial toxins: a new approach to vaccine development.

    PubMed

    Rappuoli, R; Douce, G; Dougan, G; Pizza, M

    1995-12-01

    Chemically detoxified bacterial toxins (toxoids) have been successfully used as vaccines for the prevention of many bacterial infectious diseases. Today, nontoxic derivatives of bacterial toxins can be obtained by mutagenesis of the toxin genes. These genetically inactivated toxins are superior to the classical toxoids both in safety and in immunogenicity and therefore they should replace the old toxoids in the existing vaccines. In addition, they represent a novel class of immunogens with unique properties, some of which may be used for innovative approaches to vaccination. PMID:7580303

  8. [Study on the efficacy of genetically engineered vaccines against hepatitis B for interruption of perinatal transmission].

    PubMed

    Kang, P; Shen, X M; Yu, H M

    1995-07-01

    The infectivity rate of newborn babies who had been borne from HBsAG(+), HBeAg(+) and anti-HBc(+) mothers was very high (85%). 142 babies born in the hospital were divided into three groups, in this study. In the group 1, 57 babies were inoculated with 20 micrograms recombinant DNA vaccinia vaccines against hepatitis B. The injections were given at newborn, 1 month, and 6 months, respectively. In group 2, 41 babies were inoculated with 20 micrograms genetic engineering vaccines against hepatitis B at same time were intervals as group 1. In group 3, 44 newborn babies were inoculated with 10 micrograms as same vaccines as group 2 HBIG plus 1ml (200 U/ml), at same time intervals as group 1. The immune pretection rates of newborn babies in three groups were 88.2%, 85.9% and 100%, respectively. The anti-HBs pasitive conversion rates were 82%, 86% and 98%, respectively. The group 3 was compared with group 1 and 2. Statistical analysis showed the significant differences (P < 0.05). The result showed the immune program of group 3 was superior to that of group 1 and 2, and none of the 44 babies in group 3 were infected. The efficacy of immunization by genetic engineering vaccines were superior to that of blood-derived vaccine. The genetic engineering vaccines against hepatitis B would be more useful for interruption of perinatal transmission of HBV. PMID:8631089

  9. Current Status of Syphilis Vaccine Development: Need, Challenges, Prospects

    PubMed Central

    Cameron, Caroline E.; Lukehart, Sheila A.

    2013-01-01

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community’s accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding

  10. Current status of syphilis vaccine development: need, challenges, prospects.

    PubMed

    Cameron, Caroline E; Lukehart, Sheila A

    2014-03-20

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community's accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding

  11. A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses

    PubMed Central

    Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

    2015-01-01

    Background Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a “universal” LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Methodologies/principle findings Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Conclusions/significance Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever. PMID:25884628

  12. Methods to Evaluate the Preclinical Safety and Immunogenicity of Genetically Modified Live-Attenuated Leishmania Parasite Vaccines.

    PubMed

    Gannavaram, Sreenivas; Bhattacharya, Parna; Dey, Ranadhir; Ismail, Nevien; Avishek, Kumar; Salotra, Poonam; Selvapandiyan, Angamuthu; Satoskar, Abhay; Nakhasi, Hira L

    2016-01-01

    Live-attenuated parasite vaccines are being explored as potential vaccine candidates since other approaches of vaccination have not produced an effective vaccine so far. In order for live-attenuated parasite vaccines to be tested in preclinical studies and possibly in clinical studies, the safety and immunogenicity of these organisms must be rigorously evaluated. Here we describe methods to test persistence in the immunized host and immunogenicity, and to identify biomarkers of vaccine safety and efficacy with particular reference to genetically attenuated Leishmania parasites. PMID:27076157

  13. Speciation genetics: current status and evolving approaches

    PubMed Central

    Wolf, Jochen B. W.; Lindell, Johan; Backström, Niclas

    2010-01-01

    The view of species as entities subjected to natural selection and amenable to change put forth by Charles Darwin and Alfred Wallace laid the conceptual foundation for understanding speciation. Initially marred by a rudimental understanding of hereditary principles, evolutionists gained appreciation of the mechanistic underpinnings of speciation following the merger of Mendelian genetic principles with Darwinian evolution. Only recently have we entered an era where deciphering the molecular basis of speciation is within reach. Much focus has been devoted to the genetic basis of intrinsic postzygotic isolation in model organisms and several hybrid incompatibility genes have been successfully identified. However, concomitant with the recent technological advancements in genome analysis and a newfound interest in the role of ecology in the differentiation process, speciation genetic research is becoming increasingly open to non-model organisms. This development will expand speciation research beyond the traditional boundaries and unveil the genetic basis of speciation from manifold perspectives and at various stages of the splitting process. This review aims at providing an extensive overview of speciation genetics. Starting from key historical developments and core concepts of speciation genetics, we focus much of our attention on evolving approaches and introduce promising methodological approaches for future research venues. PMID:20439277

  14. Vaccinations

    MedlinePlus

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  15. The ontology of genetic susceptibility factors (OGSF) and its application in modeling genetic susceptibility to vaccine adverse events

    PubMed Central

    2014-01-01

    Background Due to human variations in genetic susceptibility, vaccination often triggers adverse events in a small population of vaccinees. Based on our previous work on ontological modeling of genetic susceptibility to disease, we developed an Ontology of Genetic Susceptibility Factors (OGSF), a biomedical ontology in the domain of genetic susceptibility and genetic susceptibility factors. The OGSF framework was then applied in the area of vaccine adverse events (VAEs). Results OGSF aligns with the Basic Formal Ontology (BFO). OGSF defines ‘genetic susceptibility’ as a subclass of BFO:disposition and has a material basis ‘genetic susceptibility factor’. The ‘genetic susceptibility to pathological bodily process’ is a subclasses of ‘genetic susceptibility’. A VAE is a type of pathological bodily process. OGSF represents different types of genetic susceptibility factors including various susceptibility alleles (e.g., SNP and gene). A general OGSF design pattern was developed to represent genetic susceptibility to VAE and associated genetic susceptibility factors using experimental results in genetic association studies. To test and validate the design pattern, two case studies were populated in OGSF. In the first case study, human gene allele DBR*15:01 is susceptible to influenza vaccine Pandemrix-induced Multiple Sclerosis. The second case study reports genetic susceptibility polymorphisms associated with systemic smallpox VAEs. After the data of the Case Study 2 were represented using OGSF-based axioms, SPARQL was successfully developed to retrieve the susceptibility factors stored in the populated OGSF. A network of data from the Case Study 2 was constructed by using ontology terms and individuals as nodes and ontology relations as edges. Different social network analys is (SNA) methods were then applied to verify core OGSF terms. Interestingly, a SNA hub analysis verified all susceptibility alleles of SNPs and a SNA closeness analysis verified

  16. Current status and future needs in diagnostics and vaccines for high pathogenicity avian influenza.

    PubMed

    Swayne, D E; Spackman, E

    2013-01-01

    Since 1959, 32 epizootics of high pathogenicity avian influenza (HPAI) have occurred in birds. Rapid detection and accurate identification of HPAI has been critical to controlling such epizootics in poultry. Specific paradigms for the detection and diagnosis of avian influenza virus (AIV) in poultry vary somewhat among different countries and industry compartments depending on specific needs and resources. Importantly, since HPAI and low pathogenicity (LP) AI of the H5 and H7 subtypes are reportable to the World Organization for Animal Health (OIE), diagnostic procedures are implemented for regulatory purposes and are harmonized to some degree. Most current tests are adequate and have been in use for some time, therefore they have been well validated and presently there is no reported new technology that will completely replace the current tests. However, some modifications, updates or additional tests could be beneficial. The element of AIV diagnostics that is most in need of improvement is in determining the hemagglutinin and neuraminidase subtype specificity of antibody to AIV. Most HPAI epizootics have been eradicated using traditional stamping-out programs, but beginning in 1995, five epizootics have added vaccination as an additional, interim control tool. From 2002-2010, >113 billion doses of AI vaccine have been used in poultry; 95.5% as oil-emulsified, inactivated whole AIV vaccines and 4.5% as live vectored vaccines. The majority of vaccine has been used in the four H5N1 HPAI enzootic countries (China [91%], Egypt [4.7%], Indonesia [2.3%], and Vietnam [1.4%]) where vaccination programs are directed to all poultry. The 10 other countries/regions have used less than 1% of the vaccine, administered in a focused, risk- based approach. Some vaccine "failures" have resulted from antigenic drift of field viruses away from the vaccine viruses, but most have resulted from failures in the vaccination process; i.e. failure to adequately administer the vaccine to at

  17. Anti-tumor effects of genetic vaccines against HPV major oncogenes

    PubMed Central

    Cordeiro, Marcelo Nazário; Paolini, Francesca; Massa, Silvia; Curzio, Gianfranca; Illiano, Elena; Duarte Silva, Anna Jéssica; Franconi, Rosella; Bissa, Massimiliano; Morghen, Carlo De Giuli; de Freitas, Antonio Carlos; Venuti, Aldo

    2014-01-01

    Expression of HPV E5, E6 and E7 oncogenes are likely to overcome the regulation of cell proliferation and to escape immunological control, allowing uncontrolled growth and providing the potential for malignant transformation. Thus, their three oncogenic products may represent ideal target antigens for immunotherapeutic strategies. In previous attempts, we demonstrated that genetic vaccines against recombinant HPV16 E7 antigen were able to affect the tumor growth in a pre-clinical mouse model. To improve this anti-HPV strategy we developed a novel approach in which we explored the effects of E5-based genetic immunization. We designed novel HPV16 E5 genetic vaccines based on two different gene versions: whole E5 gene and E5Multi. The last one is a long multi epitope gene designed as a harmless E5 version. Both E5 genes were codon optimized for mammalian expression. In addition, we demonstrated that HPV 16 E5 oncogene is expressed in C3 mouse cell line making it an elective model for the study of E5 based vaccine. In this mouse model the immunological and biological activity of the E5 vaccines were assessed in parallel with the activity of anti-E7 and anti-E6 vaccines already reported to be effective in an immunotherapeutic setting. These E7 and E6 vaccines were made with mutated oncogenes, the E7GGG mutant that does not bind pRb and the E6F47R mutant that is less effective in inhibiting p53, respectively. Results confirmed the immunological activity of genetic formulations based on attenuated HPV16 oncogenes and showed that E5-based genetic immunization provided notable anti-tumor effects. PMID:25483514

  18. Vaccines, adjuvants and dendritic cell activators – Current Status and Future Challenges

    PubMed Central

    Obeid, Joseph M.; Hu, Yinin; Slingluff, Craig L.

    2015-01-01

    Cancer vaccines offer a low-toxicity approach to induce anticancer immune responses. They have shown promise for clinical benefit with one cancer vaccine approved in the U.S. for advanced prostate cancer. As other immune therapies are now clearly effective for treatment of advanced cancers of many histologies, there is renewed enthusiasm for optimizing cancer vaccines for use to prevent recurrence in early stage cancers and/or to combine with other immune therapies for therapy of advanced cancers. Future advancements in vaccine therapy will involve the identification and selection of effective antigen formulations, optimization of adjuvants, dendritic cell activation, and combination therapies. In this summary we present the current practice, the broad collection of challenges, and the promising future directions of vaccine therapy for cancer. PMID:26320060

  19. Antitumor Cell-Complex Vaccines Employing Genetically Modified Tumor Cells and Fibroblasts

    PubMed Central

    Miguel, Antonio; Herrero, María José; Sendra, Luis; Botella, Rafael; Diaz, Ana; Algás, Rosa; Aliño, Salvador F.

    2014-01-01

    The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok) and a low producer (p2F). Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP) IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01). When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05). Significant survival (40%) was only observed in the groups vaccinated with free transfected B16 cells. PMID:24556729

  20. Antitumor cell-complex vaccines employing genetically modified tumor cells and fibroblasts.

    PubMed

    Miguel, Antonio; Herrero, María José; Sendra, Luis; Botella, Rafael; Diaz, Ana; Algás, Rosa; Aliño, Salvador F

    2014-02-01

    The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok) and a low producer (p2F). Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP) IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01). When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05). Significant survival (40%) was only observed in the groups vaccinated with free transfected B16 cells. PMID:24556729

  1. Evolutionary reversion of live viral vaccines: Can genetic engineering subdue it?

    PubMed Central

    Bull, J. J.

    2016-01-01

    Attenuated, live viral vaccines have been extraordinarily successful in protecting against many diseases. The main drawbacks in their development and use have been reliance on an unpredictable method of attenuation and the potential for evolutionary reversion to high virulence. Methods of genetic engineering now provide many safer alternatives to live vaccines, so if live vaccines are to compete with these alternatives in the future, they must either have superior immunogenicity or they must be able to overcome these former disadvantages. Several live vaccine designs that were historically inaccessible are now feasible because of advances in genome synthesis. Some of those methods are addressed here, with an emphasis on whether they enable predictable levels of attenuation and whether they are stable against evolutionary reversion. These new designs overcome many of the former drawbacks and position live vaccines to be competitive with alternatives. Not only do new methods appear to retard evolutionary reversion enough to prevent vaccine-derived epidemics, but it may even be possible to permanently attenuate live vaccines that are transmissible but cannot evolve to higher virulence under prolonged adaptation. PMID:27034780

  2. Immunogenicity of Novel Mumps Vaccine Candidates Generated by Genetic Modification

    PubMed Central

    Xu, Pei; Chen, Zhenhai; Phan, Shannon; Pickar, Adrian

    2014-01-01

    Mumps is a highly contagious human disease, characterized by lateral or bilateral nonsuppurative swelling of the parotid glands and neurological complications that can result in aseptic meningitis or encephalitis. A mumps vaccination program implemented since the 1960s reduced mumps incidence by more than 99% and kept the mumps case numbers as low as hundreds of cases per year in the United States before 2006. However, a large mumps outbreak occurred in vaccinated populations in 2006 and again in 2009 in the United States, raising concerns about the efficacy of the vaccination program. Previously, we have shown that clinical isolate-based recombinant mumps viruses lacking expression of either the V protein (rMuVΔV) or the SH protein (rMuVΔSH) are attenuated in a neurovirulence test using newborn rat brains (P. Xu et al., Virology 417:126–136, 2011, http://dx.doi.org/10.1016/j.virol.2011.05.003; P. Xu et al., J. Virol. 86:1768–1776, 2012, http://dx.doi.org/10.1128/JVI.06019-11) and may be good candidates for vaccine development. In this study, we examined immunity induced by rMuVΔSH and rMuVΔV in mice. Furthermore, we generated recombinant mumps viruses lacking expression of both the V protein and the SH protein (rMuVΔSHΔV). Analysis of rMuVΔSHΔV indicated that it was stable in tissue culture cell lines. Importantly, rMuVΔSHΔV was immunogenic in mice, indicating that it is a promising candidate for mumps vaccine development. PMID:24352450

  3. Vaccination for Disease

    NASA Astrophysics Data System (ADS)

    Oehen, Stephan; Hengartner, Hans; Zinkernagel, Rolf M.

    1991-01-01

    Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.

  4. Current status of immunization against anthrax: old vaccines may be here to stay for a while.

    PubMed

    Turnbull, Peter C.B.

    2000-04-01

    Anthrax vaccination has become a 'hot' topic. On the one hand, fears that Iraq holds secret caches of anthrax-based weaponry, that other countries may be developing or may have developed similar devices, or that hard-line groups may make their own anthrax-based devices for bioterrorist attacks have focused official attention on the need for means of protection, principally, though, for the military. On the other hand, the unsolved issues of the Gulf War illnesses have left elements of doubt in the minds of some as to the possible role of anthrax (among other) vaccines in this syndrome, and have drawn attention to the shortage of pre-clinical, clinical, pharmacological and safety data on the existing UK and US anthrax vaccines. In the middle are those hotly debating the US and Canadian policies of mandatory anthrax immunization for military personnel or, in the case of the UK policy of voluntary immunization, simply voting with their feet. Compounding matters have been the publicized failures of the US vaccine production facility and the less publicized UK problems of supply. Meanwhile, those in genuine at-risk occupations are left unsure whether, if they can get the vaccine at all, they really want it. Despite two decades of elegant science aimed at formulating alternative vaccines to overcome all the problems of efficacy, safety and supply, such an alternative is at least five years away, and the current status is that we must live with the old vaccines or not vaccinate. PMID:11964777

  5. Genetic characteristics of Neisseria meningitidis serogroup B strains carried by adolescents living in Milan, Italy: implications for vaccine efficacy.

    PubMed

    Esposito, Susanna; Zampiero, Alberto; Terranova, Leonardo; Montinaro, Valentina; Scala, Alessia; Ansuini, Valentina; Principi, Nicola

    2013-11-01

    Before a protein vaccine is introduced into a country, it is essential to evaluate its potential impact and estimate its benefits and costs. The aim of this study was to determine the genetic characteristics of Neisseria meningitidis B (NmB) in the pharyngeal secretions of 1375 healthy adolescents aged 13-19 y living in Milan, Italy, in September 2012, and the possible protection offered by the two currently available NmB protein vaccines. Ninety-one subjects were Nm carriers (6.6%), 29 (31.9%) of whom carried the NmB capsular gene. The 29 identified strains belonged to eight clonal complexes (CCs), the majority of which were in the ST-41/44/Lin.3 CC (n = 11; 37.9%). All of the identified strains harboured ƒHbp alleles representing a total of 15 sub-variants: the gene for NHBA protein was found in all but three of the studied strains (10.3%) with 13 identified sub-variants. There were 15 porA sub-types, seven of which were identified in just one CC. The findings of this study seem to suggest that both of the protein vaccines proposed for the prevention of invasive disease due to NmB (the 4-protein and the 2-protein products) have a composition that can evoke a theoretically effective antibody response against the meningococcal strains currently carried by adolescents living in Northern Italy. The genetic characteristics of NmB strains can be easily evaluated by means of molecular methods, the results of which can provide an albeit approximate estimate of the degree of protection theoretically provided by the available vaccines, and the possible future need to change their composition. PMID:23880917

  6. Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan.

    PubMed

    Nakayama, Yoshikazu; Aruga, Atsushi

    2015-01-01

    Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region. PMID:26344953

  7. Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

    PubMed Central

    Nakayama, Yoshikazu; Aruga, Atsushi

    2015-01-01

    Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region. PMID:26344953

  8. Vaccines

    MedlinePlus Videos and Cool Tools

    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  9. Current status of the development of an AIDS vaccine.

    PubMed

    Lasky, L A

    1989-01-01

    It is commonly agreed that the development of a vaccine that would prove effective against infection by the Human Immunodeficiency Virus, HIV, would be an important measure toward eliminating the Acquired Immunodeficiency Syndrome, AIDS. The biology of HIV is complex and very little is known regarding the host immune defenses against viral infection. The virus has evolved mechanisms to evade the immune system which would appear to make traditional vaccine approaches potentially inadequate. However, all of the diverse technologies which have recently been developed in the field of vaccinology have already been applied in large measure to this disease. These techniques include the use of subunits derived from the virus or by recombinant DNA methods, the use of peptides, the use of anti-idiotypes, and the use of various attenuated viruses which can be utilized as gene carriers. This review summarizes the status of these approaches in an attempt to give a critical overview of the field as it presently exists. PMID:2673294

  10. Considerations on the current universal vaccination policy against hepatitis A in Greece after recent outbreaks.

    PubMed

    Mellou, Kassiani; Sideroglou, Theologia; Papaevangelou, Vassiliki; Katsiaflaka, Anna; Bitsolas, Nikolaos; Verykouki, Eleni; Triantafillou, Eleni; Baka, Agoritsa; Georgakopoulou, Theano; Hadjichristodoulou, Christos

    2015-01-01

    Greece is the only European Union member state that in 2008 included hepatitis A (HAV) vaccine in the routine national childhood immunization program (NCIP). Given that the resources allocated to public health have dramatically decreased since 2008 and that Greece is a low endemicity country for the disease, the benefit from universal vaccination has been questioned. The aim of this paper is to summarize the available epidemiological data of the disease for 1982-2013, and discuss the effects of universal vaccination on disease morbidity. Descriptive analysis, ARIMA modeling and time series intervention analysis were conducted using surveillance data of acute HAV. A decreasing trend of HAV notification rate over the years was identified (p<0.001). However, universal vaccination (~ 80% vaccine coverage of children) had no significant effect on the annual number of reported cases (p = 0.261) and has resulted to a progressive increase of the average age of infection in the general population. The mean age of cases before the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In the last decade, one third of all reported cases were Roma (a population accounting for 1.5% of the country's total population) and in 2013 three outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating the decreased effectiveness of the current immunization strategy in this group. Data suggest that universal vaccination may need to be re-considered. Probably a more cost effective approach would be to implement a program that will include: a) vaccination of high risk groups, b) universal vaccination of Roma children and improving conditions at Roma camps, c) education of the population and travel advice, and d) enhancement of the control measures to increase safety of shellfish and other foods. PMID:25590132

  11. Vaccine industry perspective of current issues of good manufacturing practices regarding product inspections and stability testing.

    PubMed

    Monahan, T R

    2001-12-15

    I address 2 important topics of current good manufacturing practices as they apply to vaccine products: product inspections and stability testing. The perspective presented is that of regulated industry. There are 2 major categories of product/facility inspections: those occurring before licensure of a vaccine product and those occurring after a vaccine product is licensed. The logistics and focus of each inspection type, the preapproval inspection, and the required biennial inspection are discussed, as are guidance and recommendations for achieving successful inspections. The requirements, guidance, and recommendations regarding the type, amount, and extensiveness of stability data for vaccine products are presented. The discussion details the potential differences in the amount and type of data required for products that are not yet licensed versus marketed products. Guidance, from a regulated industry perspective, regarding the design and implementation of a successful stability program is also discussed. PMID:11709773

  12. Genetic variation in the Plasmodium falciparum circumsporozoite protein in India and its relevance to RTS,S malaria vaccine.

    PubMed

    Zeeshan, Mohammad; Alam, Mohammad Tauqeer; Vinayak, Sumiti; Bora, Hema; Tyagi, Rupesh Kumar; Alam, Mohd Shoeb; Choudhary, Vandana; Mittra, Pooja; Lumb, Vanshika; Bharti, Praveen Kumar; Udhayakumar, Venkatachalam; Singh, Neeru; Jain, Vidhan; Singh, Pushpendra Pal; Sharma, Yagya Dutta

    2012-01-01

    RTS,S is the most advanced malaria vaccine candidate, currently under phase-III clinical trials in Africa. This Plasmodium falciparum vaccine contains part of the central repeat region and the complete C-terminal T cell epitope region (Th2R and Th3R) of the circumsporozoite protein (CSP). Since naturally occurring polymorphisms at the vaccine candidate loci are critical determinants of the protective efficacy of the vaccines, it is imperative to investigate these polymorphisms in field isolates. In this study we have investigated the genetic diversity at the central repeat, C-terminal T cell epitope (Th2R and Th3R) and N-terminal T cell epitope regions of the CSP, in P. falciparum isolates from Madhya Pradesh state of India. These isolates were collected through a 5-year prospective study aimed to develop a well-characterized field-site for the future evaluation of malaria vaccine in India. Our results revealed that the central repeat (63 haplotypes, n = 161) and C-terminal Th2R/Th3R epitope (24 haplotypes, n = 179) regions were highly polymorphic, whereas N-terminal non-repeat region was less polymorphic (5 haplotypes, n = 161) in this population. We did not find any evidence of the role of positive natural selection in maintaining the genetic diversity at the Th2R/Th3R regions of CSP. Comparative analysis of the Th2R/Th3R sequences from this study to the global isolates (n = 1160) retrieved from the GenBank database revealed two important points. First, the majority of the sequences (~61%, n = 179) from this study were identical to the Dd2/Indochina type, which is also the predominant Th2R/Th3R haplotype in Asia (~59%, n = 974). Second, the Th2R/Th3R sequences in Asia, South America and Africa are geographically distinct with little allele sharing between continents. In conclusion, this study provides an insight on the existing polymorphisms in the CSP in a parasite population from India that could potentially influence the efficacy of RTS,S vaccine in this

  13. Antigenic and Genetic Evolution of Low-Pathogenicity Avian Influenza Viruses of Subtype H7N3 following Heterologous Vaccination

    PubMed Central

    Xu, Yifei; Long, Li-Ping; Capua, Ilaria; Wan, Xiu-Feng

    2014-01-01

    Outbreaks of low-pathogenicity avian influenza (LPAI) viruses of the H7N3 subtype were first detected in Italy in October 2002, and the virus continued to circulate between 2002 and 2004 in a densely populated poultry area in the northeast portion of that country. This virus circulated in unvaccinated and vaccinated poultry farms, and the infection was controlled in August 2003 by culling, control of movements, improved biosecurity, and heterologous vaccination. In 2004, H7N3 reoccurred in vaccinated poultry farms in which infection had been successfully controlled by the vaccination program. To shed light on this occurrence and the temporal pattern and genetic basis of antigenic drift for avian influenza viruses (AIVs) in the absence and presence of heterologous vaccination, a collection of H7N3 viruses isolated in 2002 and 2004 were characterized genetically and antigenically. Molecular analysis showed that viruses isolated in the 2004 outbreaks after the implementation of vaccination had acquired specific amino acid signatures, most of which were located at reported antibody binding sites of the hemagglutinin (HA) protein. Antigenic characterization of these 2004 isolates showed that they were antigenically different from those isolated prior to the implementation of vaccination. This is the first report on antigenic and genetic evolution of H7 LPAI viruses following the application of heterologous vaccination in poultry. These findings may have an impact on control strategies to combat AI infections in poultry based on vaccination. PMID:24554694

  14. Improving the immunogenicity of a trivalent Neisseria meningitidis native outer membrane vesicle vaccine by genetic modification.

    PubMed

    Zhang, Lan; Wen, Zhiyun; Lin, Jing; Xu, Hui; Herbert, Paul; Wang, Xin-Min; Mehl, John T; Ahl, Patrick L; Dieter, Lance; Russell, Ryann; Kosinski, Mike J; Przysiecki, Craig T

    2016-07-29

    Trivalent native outer membrane vesicles (nOMVs) derived from three genetically modified Neisseria meningitidis serogroup B strains have been previously evaluated immunologically in mice and rabbits. This nOMV vaccine elicited serum bactericidal activity (SBA) against multiple N. meningitidis serogroup B strains as well as strains from serogroups C, Y, W, and X. In this study, we used trivalent nOMVs isolated from the same vaccine strains and evaluated their immunogenicity in an infant Rhesus macaque (IRM) model whose immune responses to the vaccine are likely to be more predictive of the responses in human infants. IRMs were immunized with trivalent nOMV vaccines and sera were evaluated for exogenous human serum complement-dependent SBA (hSBA). Antibody responses to selected hSBA generating antigens contained within the trivalent nOMVs were also measured and we found that antibody titers against factor H binding protein variant 2 (fHbpv2) were very low in the sera from animals immunized with these original nOMV vaccines. To increase the fHbp content in the nOMVs, the vaccine strains were further genetically altered by addition of another fHbp gene copy into the porB locus. Trivalent nOMVs from the three new vaccine strains had higher fHbp antigen levels and generated higher anti-fHbp antibody responses in immunized mice and IRMs. As expected, fHbp insertion into the porB locus resulted in no PorB expression. Interestingly, higher expression of PorA, an hSBA generating antigen, was observed for all three modified vaccine strains. Compared to the trivalent nOMVs from the original strains, higher PorA levels in the improved nOMVs resulted in higher anti-PorA antibody responses in mice and IRMs. In addition, hSBA titers against other strains with PorA as the only hSBA antigen in common with the vaccine strains also increased. PMID:27269057

  15. Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development.

    PubMed

    Blake, Damer P; Clark, Emily L; Macdonald, Sarah E; Thenmozhi, Venkatachalam; Kundu, Krishnendu; Garg, Rajat; Jatau, Isa D; Ayoade, Simeon; Kawahara, Fumiya; Moftah, Abdalgader; Reid, Adam James; Adebambo, Ayotunde O; Álvarez Zapata, Ramón; Srinivasa Rao, Arni S R; Thangaraj, Kumarasamy; Banerjee, Partha S; Dhinakar-Raj, G; Raman, M; Tomley, Fiona M

    2015-09-22

    The phylum Apicomplexa includes serious pathogens of humans and animals. Understanding the distribution and population structure of these protozoan parasites is of fundamental importance to explain disease epidemiology and develop sustainable controls. Predicting the likely efficacy and longevity of subunit vaccines in field populations relies on knowledge of relevant preexisting antigenic diversity, population structure, the likelihood of coinfection by genetically distinct strains, and the efficiency of cross-fertilization. All four of these factors have been investigated for Plasmodium species parasites, revealing both clonal and panmictic population structures with exceptional polymorphism associated with immunoprotective antigens such as apical membrane antigen 1 (AMA1). For the coccidian Toxoplasma gondii only genomic diversity and population structure have been defined in depth so far; for the closely related Eimeria species, all four variables are currently unknown. Using Eimeria tenella, a major cause of the enteric disease coccidiosis, which exerts a profound effect on chicken productivity and welfare, we determined population structure, genotype distribution, and likelihood of cross-fertilization during coinfection and also investigated the extent of naturally occurring antigenic diversity for the E. tenella AMA1 homolog. Using genome-wide Sequenom SNP-based haplotyping, targeted sequencing, and single-cell genotyping, we show that in this coccidian the functionality of EtAMA1 appears to outweigh immune evasion. This result is in direct contrast to the situation in Plasmodium and most likely is underpinned by the biology of the direct and acute coccidian life cycle in the definitive host. PMID:26354122

  16. Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development

    PubMed Central

    Blake, Damer P.; Clark, Emily L.; Macdonald, Sarah E.; Thenmozhi, Venkatachalam; Kundu, Krishnendu; Garg, Rajat; Jatau, Isa D.; Ayoade, Simeon; Kawahara, Fumiya; Moftah, Abdalgader; Reid, Adam James; Adebambo, Ayotunde O.; Álvarez Zapata, Ramón; Srinivasa Rao, Arni S. R.; Thangaraj, Kumarasamy; Banerjee, Partha S.; Dhinakar-Raj, G.; Raman, M.; Tomley, Fiona M.

    2015-01-01

    The phylum Apicomplexa includes serious pathogens of humans and animals. Understanding the distribution and population structure of these protozoan parasites is of fundamental importance to explain disease epidemiology and develop sustainable controls. Predicting the likely efficacy and longevity of subunit vaccines in field populations relies on knowledge of relevant preexisting antigenic diversity, population structure, the likelihood of coinfection by genetically distinct strains, and the efficiency of cross-fertilization. All four of these factors have been investigated for Plasmodium species parasites, revealing both clonal and panmictic population structures with exceptional polymorphism associated with immunoprotective antigens such as apical membrane antigen 1 (AMA1). For the coccidian Toxoplasma gondii only genomic diversity and population structure have been defined in depth so far; for the closely related Eimeria species, all four variables are currently unknown. Using Eimeria tenella, a major cause of the enteric disease coccidiosis, which exerts a profound effect on chicken productivity and welfare, we determined population structure, genotype distribution, and likelihood of cross-fertilization during coinfection and also investigated the extent of naturally occurring antigenic diversity for the E. tenella AMA1 homolog. Using genome-wide Sequenom SNP-based haplotyping, targeted sequencing, and single-cell genotyping, we show that in this coccidian the functionality of EtAMA1 appears to outweigh immune evasion. This result is in direct contrast to the situation in Plasmodium and most likely is underpinned by the biology of the direct and acute coccidian life cycle in the definitive host. PMID:26354122

  17. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    PubMed Central

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-01-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host’s immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host’s immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  18. Immunogenicity and efficacy of a plasmid DNA rabies vaccine incorporating Myd88 as a genetic adjuvant

    PubMed Central

    Ullas, Padinjaremattathil Thankappan; Desai, Anita

    2014-01-01

    Purpose Myeloid differentiation factor 88 (Myd88), a ubiquitous Toll-like receptor adaptor molecule, has been reported to play important roles in B cell responses to infections and vaccination. The present study evaluated the effects of genetic adjuvanting with Myd88 on the immune responses to a plasmid DNA rabies vaccine. Materials and Methods Plasmids encoding rabies glycoprotein alone (pIRES-Rgp) or a fragment of Myd88 gene in addition (pIRES-Rgp-Myd) were constructed and administered intramuscularly or intrademally in Swiss albino mice (on days 0, 7, and 21). Rabies virus neutralizing antibody (RVNA) titres were estimated in the mice sera on days 14 and 28 by rapid fluorescent focus inhibition test. The protective efficacy of the constructs was evaluated by an intracerebral challenge with challenge virus standard virus on day 35. Results Co-expression of Myd88 increased RVNA responses to pIRES-Rgp by 3- and 2-folds, following intramuscular and intradermal immunization, respectively. pIRES-Rgp protected 80% of the mice following intramuscular and intradermal immunizations, while pIRES-Rgp-Myd afforded 100% protection following similar administrations. Conclusion Genetic adjuvanting with Myd88 enhanced the RVNA responses and protective efficacy of a plasmid DNA rabies vaccine. This strategy might be useful for rabies vaccination of canines in the field, and needs further evaluation. PMID:25003094

  19. Genetic Vaccine for Respiratory Syncytial Virus Provides Protection Without Disease Potentiation

    PubMed Central

    Johnson, Teresa R; Rangel, David; Graham, Barney S; Brough, Douglas E; Gall, Jason G

    2014-01-01

    Respiratory syncytial virus (RSV) is a major cause of infectious lower respiratory disease in infants and the elderly. As there is no vaccine for RSV, we developed a genetic vaccine approach that induced protection of the entire respiratory tract from a single parenteral administration. The approach was based on adenovirus vectors derived from newly isolated nonhuman primate viruses with low seroprevalence. We show for the first time that a single intramuscular (IM) injection of the replication-deficient adenovirus vectors expressing the RSV fusion (F0) glycoprotein induced immune responses that protected both the lungs and noses of cotton rats and mice even at low doses and for several months postimmunization. The immune response included high titers of neutralizing antibody that were maintained ≥24 weeks and RSV-specific CD8+ and CD4+ T cells. The vectors were as potently immunogenic as a human adenovirus 5 vector in these two key respiratory pathogen animal models. Importantly, there was minimal alveolitis and granulocytic infiltrates in the lung, and type 2 cytokines were not produced after RSV challenge even under conditions of partial protection. Overall, this genetic vaccine is highly effective without potentiating immunopathology, and the results support development of the vaccine candidate for human testing. PMID:23752342

  20. Genetic Vaccination against Experimental Infection with Myotropic Parasite Strains of Trypanosoma cruzi

    PubMed Central

    Araújo, Adriano Fernando; de Oliveira, Gabriel; Vasconcelos, Juliana Fraga; Ersching, Jonatan; Dominguez, Mariana Ribeiro; Vasconcelos, José Ronnie; Machado, Alexandre Vieira; Gazzinelli, Ricardo Tostes; Bruna-Romero, Oscar; Soares, Milena Botelho; Rodrigues, Mauricio Martins

    2014-01-01

    In earlier studies, we reported that a heterologous prime-boost regimen using recombinant plasmid DNA followed by replication-defective adenovirus vector, both containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote surface protein (ASP) 2, provided protective immunity against experimental infection with a reticulotropic strain of this human protozoan parasite. Herein, we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged with myotropic parasite strains (Brazil and Colombian). Initially, we determined that the coadministration during priming of a DNA plasmid containing the murine IL-12 gene improved the immune response and was essential for protective immunity elicited by the heterologous prime-boost regimen in susceptible male mice against acute lethal infections with these parasites. The prophylactic or therapeutic vaccination of resistant female mice led to a drastic reduction in the number of inflammatory infiltrates in cardiac and skeletal muscles during the chronic phase of infection with either strain. Analysis of the electrocardiographic parameters showed that prophylactic vaccination reduced the frequencies of sinus arrhythmia and atrioventricular block. Our results confirmed that prophylactic vaccination using the TS and ASP-2 genes benefits the host against acute and chronic pathologies caused by T. cruzi and should be further evaluated for the development of a veterinary or human vaccine against Chagas disease. PMID:25061263

  1. Immunomodulatory vaccination in autoimmune disease.

    PubMed

    Urbanek-Ruiz, Irene; Ruiz, Pedro J; Steinman, Lawrence; Fathman, C Garrison

    2002-06-01

    The development of vaccines is arguably the most significant achievement in medicine to date. The practice of innoculation with the fluid from a sore to protect from a disease actually dates back to ancient China; however, with the introduction of Jenner's smallpox vaccine, and greater understanding of the immune system, vaccines have become specific and systematic. Traditional vaccines have used killed pathogens (hepatitis A and the Salk polio vaccines), immunogenic subunits of a given pathogen (hepatitis B subunit vaccine), or live attenuated pathogens (measles, mumps, rubella, Sabin polio vaccines) to generate protective immunity. Currently, a new generation of vaccines that use the genetic material of a pathogen to elicit protective immunity are being developed. Although the most widespread and successful use of vaccines today remains in the arena of infectious diseases, manipulations of immune responses to protect against cancers, neurologic diseases, and autoimmunity are being explored rigorously. PMID:12092460

  2. Towards a Preventive Strategy for Toxoplasmosis: Current Trends, Challenges, and Future Perspectives for Vaccine Development.

    PubMed

    Fereig, Ragab M; Nishikawa, Yoshifumi

    2016-01-01

    With its facultative ability to induce various types of infection in its hosts, Toxoplasma gondii remains a fascinating and enigmatic pathogen. As a parasite, despite its primitive unicellular structure, it possesses a highly sophisticated arsenal of invasive and defensive tools. Toxoplasmosis has gained widespread significance as a zoonotic disease capable of inducing severe illnesses in humans and drastic economic losses in the veterinary field. Although around a third of the world's population is infected with Toxoplasma gondii, immunocompromised people, pregnant women, and neonates are more vulnerable to the most severe forms of the disease. Hence, development of a preventive strategy is urgently needed to combat T. gondii infection in both humans and animals. Successful triggering of host immune responses and development of specific immune responses against the different strains and antigens of T. gondii has encouraged researchers to focus on vaccination as a feasible preventive control strategy against toxoplasmosis. In the last few years, vaccine development against T. gondii infections has seen great advances and achievements being made at the research level and, to a lesser extent, in veterinary applications. Currently, only one live attenuated vaccine is available for reducing abortions and fetal losses in pregnant ewes. Otherwise, researchers have investigated numerous classes of vaccine, including live attenuated, recombinant subunit, and vectored. In this chapter we discuss the most commonly investigated vaccines against toxoplasmosis, recombinant DNA and protein vaccines, with special focus on their methodologies and mechanisms of action. PMID:27076296

  3. Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax

    PubMed Central

    2012-01-01

    Background A major concern in malaria vaccine development is genetic polymorphisms typically observed among Plasmodium isolates in different geographical areas across the world. Highly polymorphic regions have been observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins such as Circumsporozoite protein (CSP), Duffy-binding protein (DBP), Merozoite surface protein-1 (MSP-1), Apical membrane antigen-1 (AMA-1) and Thrombospondin related anonymous protein (TRAP). Methods Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens in P. vivax among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. Results The structured diversity found in P. vivax populations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of the trap, dbp and ama-1 genes. Conclusions It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity. PMID:22417572

  4. Genetic Diversity Underlying the Envelope Glycoproteins of Hepatitis C Virus: Structural and Functional Consequences and the Implications for Vaccine Design

    PubMed Central

    Tarr, Alexander W.; Khera, Tanvi; Hueging, Kathrin; Sheldon, Julie; Steinmann, Eike; Pietschmann, Thomas; Brown, Richard J. P.

    2015-01-01

    In the 26 years since the discovery of Hepatitis C virus (HCV) a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA) regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design. PMID:26193307

  5. Genetic Diversity Underlying the Envelope Glycoproteins of Hepatitis C Virus: Structural and Functional Consequences and the Implications for Vaccine Design.

    PubMed

    Tarr, Alexander W; Khera, Tanvi; Hueging, Kathrin; Sheldon, Julie; Steinmann, Eike; Pietschmann, Thomas; Brown, Richard J P

    2015-07-01

    In the 26 years since the discovery of Hepatitis C virus (HCV) a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA) regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design. PMID:26193307

  6. Genetic diversity of the Pneumococcal CbpA: Implications for next-generation vaccine development

    PubMed Central

    Abry, Muna F; Kimenyi, Kelvin M; Osowo, Fred O; Odhiambo, Willingtone O; Sewe, Steven O; Kulohoma, Benard W

    2015-01-01

    Pneumococci are capable of vaccine escape by genetic recombination at the targeted capsular locus, significantly reducing long-term vaccine effectiveness. Recently, efforts have been redirected to understanding pneumococcal biology related to potential next-generation vaccine candidates. A variety of serotype-independent protein antigens capable of inducing protective immune responses in tissue culture and animal models of infection have been identified. However, ideal vaccine candidates that are conserved across all genotypes, provide broad population coverage, and induce T-cell dependent immune responses are still under investigation. We examined whether immune responses due to the highly polymorphic CbpA antigen are due to a conserved domain capable of evoking specific immune “memory” across all genotypes of pneumococci. We defined the genotypes in a global dataset of 213 pneumococcal isolates. This isolate collection was genotypically diverse and ideal for establishing the presence of conserved CbpA epitopes as potential protein vaccine candidates. Examination of the CbpA locus sequence was highly polymorphic at both the nucleic acid and amino acid level. Despite this high polymorphism some domains are broadly conserved and consist of different amino acid residues with the same physicochemical properties, and therefore have similar tertiary structures. The two most common domains identified in the CbpA gene are modular teichoic acid phosphorylcholine esterase Pce (2bib:A), and R2 domain (1w9r:A). These conserved domains are immunogenic, therefore capable of inducing long-term host immune responses; moreover they are extracellularly located and thus accessible. We proposed their evaluation as suitable next-generation CbpA-fusion protein vaccine candidates. PMID:25902300

  7. Rough vaccines in animal brucellosis: structural and genetic basis and present status.

    PubMed

    Moriyón, Ignacio; Grilló, María Jesús; Monreal, Daniel; González, David; Marín, Clara; López-Goñi, Ignacio; Mainar-Jaime, Raúl C; Moreno, Edgardo; Blasco, José María

    2004-01-01

    Brucellosis control and eradication requires serological tests and vaccines. Effective classical vaccines (S19 in cattle and Rev 1 in small ruminants), however, induce antibodies to the O-polysaccharide of the lipopolysaccharide which may be difficult to distinguish from those resulting from infection and may thus complicate diagnosis. Rough attenuated mutants lack the O-polysaccharide and would solve this problem if eliciting protective immunity; the empirically obtained rough mutants 45/20 and RB51 have been used as vaccines. Strain 45/20 is reportedly unstable and it is not presently used. RB51 is increasingly used instead of S19 in some countries but it is rifampicin resistant and its effectiveness is controversial. Some controlled experiments have found good or absolute protection in adult cattle vaccinated orally (full dose) or subcutaneously (reduced dose) and in one field experiment, RB51 was reported to afford absolute protection to calves and to perform better than S19. Controlled experiments in calves, however, have shown reduced doses of RB51 to be ineffective, full doses only partially effective, and RB51 less effective than S19 against severe challenges. Moreover, other observations suggest that RB51 is ineffective when prevalence is high. RB51 is not useful in sheep and evidence in goats is preliminary and contradictory. Rough mutants obtained by molecular biology methods on the knowledge of the genetics and structure of Brucella lipopolysaccharide may offer alternatives. The B. abortus manBcore (rfbK) mutant seems promising in cattle, and analyses in mice suggest that mutations affecting only the O-polysaccharide result in better vaccines than those affecting both core and O-polysaccharide. Possible uses of rough vaccines also include boosting immunity by revaccination but solid evidence on its effectiveness, safety and practicality is not available. PMID:15099501

  8. Childhood and adolescent influenza vaccination in Europe: A review of current policies and recommendations for the future.

    PubMed

    McGuire, Alistair; Drummond, Mike; Keeping, Sam

    2016-05-01

    Children and adolescents experience some of the highest rates of influenza infection and the subsequent burden on both infected children and their parents/carers is substantial. Vaccinating children and adolescents against seasonal influenza has the potential to reduce the burden of disease in both vaccinated and unvaccinated individuals due to the pivotal role that younger age groups play in the transmission of infection. While countries such as the USA, Canada and the UK have consequently recommended the universal vaccination of children, the vast majority of European countries have not yet extended their vaccination policies to this age group. This review examines the rationale for childhood and adolescent vaccination against seasonal influenza and reviews current vaccination policies in Europe. We discuss key policy considerations for European countries that must be considered when extending vaccination programmes to younger age groups alongside recommendations for European policy makers based on our findings. PMID:26879817

  9. International regulatory requirements for Leptospira vaccine potency testing. Roundtable: current requirements and opportunity for harmonization.

    PubMed

    Draayer, Hans A; Bruckner, Lukas; Peña-Moctezuma, Alejandro de la; Srinivas, Geetha

    2013-09-01

    Progress continues to be made in the ongoing efforts to replace, reduce, or refine the use of laboratory animals for Leptospira vaccine potency testing in certain markets/regions. Leptospira-containing vaccines, as with many veterinary vaccines, are manufactured and distributed both on a regional basis by local manufacturers and internationally by large multinational firms. Three general scenarios exist for the international testing and distribution of veterinary vaccines including: 1) the importing country recognizes the country of origin's testing and batch release data with no additional testing; 2) the importing country requires the manufacturer to conduct a specific potency assay based on the current importing market's regulations for the importing country or 3) the importing country requires retesting of the product in country prior to distribution. Scenarios 2 and 3 both have the potential to significantly increase the usage of laboratory animals for what may be considered redundant testing. Specific requirements for the importation of Leptospira vaccines in the United States, Europe, and Mexico were presented as well as efforts to reduce the use of laboratory animal testing through the availability of internationally recognized tests. PMID:23890730

  10. Current rabies vaccines and prophylaxis schedules: preventing rabies before and after exposure.

    PubMed

    Warrell, M J

    2012-01-01

    Travellers are probably the largest group in the general population to receive rabies pre-exposure prophylaxis. The dangerous consequences of the unavailability of rabies immune globulin in many countries could be ameliorated if pre-exposure rabies vaccination were practised more widely, especially in children, living in dog rabies enzootic countries. The WHO has recommended several different regimens for post-exposure prophylaxis, while individual countries decide on protocols for local use. Intramuscular regimens are expensive and waste vaccine. Although failure to receive vaccine is usually the due to the cost, the economical potential of intradermal vaccination has still not been realised 19 years after its introduction. The currently recommended 2-site intradermal post-exposure regimen is not economical for use in rural areas where 80% of Indian rabies deaths occur. Most countries using it demand higher potency vaccine, indicating that they do not have complete confidence in the method. This intradermal regimen has only been used where immunoglobulin is likely to be available for severely bitten patients. Increased intradermal doses are sometimes used for selected patients. Provision of economical rabies prophylaxis can be improved. Decisions to change recommendations should take account of the immunological, financial, practical and logistical aspects of dog bite treatment in remote areas. PMID:22342356

  11. Genetic characterisation of the rabies virus vaccine strains used for oral immunization of foxes in Poland to estimate the effectiveness of vaccination.

    PubMed

    Orłowska, Anna; Żmudziński, Jan Franciszek

    2015-02-01

    The main reservoir of rabies virus in Poland has been the red fox. To control rabies in wildlife, oral immunization of foxes was introduced in 1993. The vaccine is effective when it confers immunity against the virus circulating in the environment. To assess the above issue, a study of the molecular characteristics of 570-bp fragments of the N and G genes of vaccine strains SAD B19 and SAD Bern against street virus strains was performed. The results confirmed the similarity of the vaccine strains and rabies virus strains circulating in the environment and also demonstrate the genetic stability of vaccine strains that have been distributed in Poland for 20 years. PMID:25408374

  12. A Reverse Genetics Approach for the Design of Methyltransferase-Defective Live Attenuated Avian Metapneumovirus Vaccines.

    PubMed

    Zhang, Yu; Sun, Jing; Wei, Yongwei; Li, Jianrong

    2016-01-01

    Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. aMPV belongs to the family Paramyxoviridae which includes many important human pathogens such as human respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (PIV3). The family also includes highly lethal emerging pathogens such as Nipah virus and Hendra virus, as well as agriculturally important viruses such as Newcastle disease virus (NDV). For many of these viruses, there is no effective vaccine. Here, we describe a reverse genetics approach to develop live attenuated aMPV vaccines by inhibiting the viral mRNA cap methyltransferase. The viral mRNA cap methyltransferase is an excellent target for the attenuation of paramyxoviruses because it plays essential roles in mRNA stability, efficient viral protein translation and innate immunity. We have described in detail the materials and methods used to generate recombinant aMPVs that lack viral mRNA cap methyltransferase activity. We have also provided methods to evaluate the genetic stability, pathogenesis, and immunogenicity of live aMPV vaccine candidates in turkeys. PMID:27076293

  13. Current and future effects of varicella and herpes zoster vaccination in Germany - Insights from a mathematical model in a country with universal varicella vaccination.

    PubMed

    Horn, Johannes; Karch, André; Damm, Oliver; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Hengel, Hartmut; Greiner, Wolfgang; Mikolajczyk, Rafael T

    2016-07-01

    Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies. PMID:26835890

  14. Expanding the Repertoire of Modified Vaccinia Ankara-Based Vaccine Vectors via Genetic Complementation Strategies

    PubMed Central

    Garber, David A.; O'Mara, Leigh A.; Zhao, Jun; Gangadhara, Sailaja; An, InChul; Feinberg, Mark B.

    2009-01-01

    Background Modified Vaccinia virus Ankara (MVA) is a safe, highly attenuated orthopoxvirus that is being developed as a recombinant vaccine vector for immunization against a number of infectious diseases and cancers. However, the expression by MVA vectors of large numbers of poxvirus antigens, which display immunodominance over vectored antigens-of-interest for the priming of T cell responses, and the induction of vector-neutralizing antibodies, which curtail the efficacy of subsequent booster immunizations, remain as significant impediments to the overall utility of such vaccines. Thus, genetic approaches that enable the derivation of MVA vectors that are antigenically less complex may allow for rational improvement of MVA-based vaccines. Principal Findings We have developed a genetic complementation system that enables the deletion of essential viral genes from the MVA genome, thereby allowing us to generate MVA vaccine vectors that are antigenically less complex. Using this system, we deleted the essential uracil-DNA-glycosylase (udg) gene from MVA and propagated this otherwise replication-defective variant on a complementing cell line that constitutively expresses the poxvirus udg gene and that was derived from a newly identified continuous cell line that is permissive for growth of wild type MVA. The resulting virus, MVAΔudg, does not replicate its DNA genome or express late viral gene products during infection of non-complementing cells in culture. As proof-of-concept for immunological ‘focusing’, we demonstrate that immunization of mice with MVAΔudg elicits CD8+ T cell responses that are directed against a restricted repertoire of vector antigens, as compared to immunization with parental MVA. Immunization of rhesus macaques with MVAΔudg-gag, a udg− recombinant virus that expresses an HIV subtype-B consensus gag transgene, elicited significantly higher frequencies of Gag-specific CD8 and CD4 T cells following both primary (2–4-fold) and booster (2

  15. Vaccine Safety

    MedlinePlus

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  16. Vaccines

    MedlinePlus Videos and Cool Tools

    ... help the body defend itself against foreign invaders. As the antigens invade the body's tissues, they attract ... the suppressor T cells stop the attack. After a vaccination, the body will have a memory of ...

  17. Leishmania tropica major in mice: vaccination against cutaneous leishmaniasis in mice of high genetic susceptibility.

    PubMed

    Mitchell, G F; Handman, E

    1983-02-01

    BALB/c and BALB/c.H-2b mice are genetically susceptible to development of persistent and severe disease following cutaneous injection of promastigotes of the protozoan parasite, Leishmania tropica major, whereas C57BL/6 are relatively resistant. Resistance in C57BL/6 can be further increased by intraperitoneal injection of living, but not killed, promastigotes prior to cutaneous challenge. Severely diseased BALB/c mice can show resistance to development of a second cutaneous lesion but apparently only in the advanced stages of systemic life-threatening disease. A striking level of resistance to persistent disease has been demonstrated in BALB/c.H-2b mice pre-injected with frozen and thawed L. t. major-infected macrophages of the continuous macrophage cell line IC-21 (H-2b) together with Corynebacterium parvum. No resistance is seen in recipients of either C. parvum or the crude antigen mixture alone. Protection is afforded by intraperitoneal and not subcutaneous injection of crude antigen plus adjuvant. In these vaccination studies all evidence points to the infected macrophage as most appropriate source of 'host-protective' antigens as well as being the most likely target of host-protective immunity. Resistance is expressed in vaccinated mice as minimal signs of cutaneous disease and rapid resolution of any small lesions which do develop. Frozen and thawed promastigotes plus C. parvum will not induce resistance to persistent disease in BALB/c.H-2b mice and preincubation of promastigotes with sera from resistant vaccinated mice does not influence their capacity to cause cutaneous disease. The results provide baseline data for vaccination attempts in genetically susceptible hosts using isolated L. t. major antigens (and, in particular, infected macrophage antigens) and highlight the utility of the intraperitoneal route of injection and the use of the therapeutic biological, C. parvum, as an adjuvant in such studies. PMID:6870673

  18. Genetic distribution of noncapsular meningococcal group B vaccine antigens in Neisseria lactamica.

    PubMed

    Lucidarme, Jay; Gilchrist, Stefanie; Newbold, Lynne S; Gray, Stephen J; Kaczmarski, Edward B; Richardson, Lynne; Bennett, Julia S; Maiden, Martin C J; Findlow, Jamie; Borrow, Ray

    2013-09-01

    The poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genus Neisseria that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal, Neisseria lactamica. All the isolates possessed nhba but were devoid of fhbp and nadA. The nhba alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented. PMID:23803905

  19. A non-human hepadnaviral adjuvant for hepatitis C virus-based genetic vaccines.

    PubMed

    Levander, Sepideh; Sällberg, Matti; Ahlén, Gustaf; Frelin, Lars

    2016-05-27

    Human hepatitis B virus (HBV) core antigen (HBcAg) can act as an adjuvant in hepatitis C virus (HCV)-based DNA vaccines. Since two billion people are, or have been, in contact with HBV, one may question the use of human HBV sequences as adjuvant. We herein evaluated non-human stork hepatitis B virus core gene-sequences from stork as DNA vaccine adjuvants. Full-length and fragmented stork HBcAg gene-sequences were added to an HCV non-structural (NS) 3/4A gene (NS3/4A-stork-HBcAg). This resulted in an enhanced priming of HCV-specific IFN-γ and IL-2 responses in both wild-type (wt)- and NS3/4A-transgenic (Tg) mice, the latter with dysfunctional NS3/4A-specific T cells. The NS3/4A-stork-HBcAg vaccine primed NS3/4A-specific T cells in hepatitis B e antigen (HBeAg)-Tg mice with dysfunctional T cells to HBcAg and HBeAg. Repeated immunizations boosted expansion of IFN-γ and IL-2-producing NS3/4A-specific T cells in wt- and NS3/4A-Tg mice. Importantly, NS3/4A-stork-HBcAg-DNA induced in vivo long-term functional memory T cell responses, whose maintenance required CD4(+) T cells. Thus, avian HBcAg gene-sequences from stork can effectively act as a DNA vaccine adjuvant. This technology can most likely be universally expanded to other genetic vaccine antigens, as this completely avoids the use of sequences from a human virus where a pre-existing immunity may interfere with its adjuvant effect. PMID:27109565

  20. Protection against exotic Newcastle disease virus (NDV) challenge of chickens vaccinated with NDV vaccines made from different genetic lineages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines for control of Newcastle Disease (ND) have been used for over fifty years in the United States. The available ND vaccines, both live and killed have been shown to prevent mortality and symptoms of disease. However, they typically do not prevent vaccinated birds from becoming infected and ...

  1. Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches.

    PubMed

    Aschenbroich, Sophie A; Lafontaine, Eric R; Hogan, Robert J

    2016-09-01

    Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures. PMID:27010618

  2. Current status of meningococcal group B vaccine candidates: capsular or noncapsular?

    PubMed Central

    Diaz Romero, J; Outschoorn, I M

    1994-01-01

    Meningococcal meningitis is a severe, life-threatening infection for which no adequate vaccine exists. Current vaccines, based on the group-specific capsular polysaccharides, provide short-term protection in adults against serogroups A and C but are ineffective in infants and do not induce protection against group B strains, the predominant cause of infection in western countries, because the purified serogroup B polysaccharide fails to elicit human bactericidal antibodies. Because of the poor immunogenicity of group B capsular polysaccharide, different noncapsular antigens have been considered for inclusion in a vaccine against this serogroup: outer membrane proteins, lipooligosaccharides, iron-regulated proteins, Lip, pili, CtrA, and the immunoglobulin A proteases. Alternatively, attempts to increase the immunogenicity of the capsular polysaccharide have been made by using noncovalent complexes with outer membrane proteins, chemical modifications, and structural analogs. Here, we review the strategies employed for the development of a vaccine for Neisseria meningitidis serogroup B; the difficulties associated with the different approaches are discussed. PMID:7834605

  3. A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites.

    PubMed

    van Schaijk, Ben C L; Ploemen, Ivo H J; Annoura, Takeshi; Vos, Martijn W; Foquet, Lander; van Gemert, Geert-Jan; Chevalley-Maurel, Severine; van de Vegte-Bolmer, Marga; Sajid, Mohammed; Franetich, Jean-Francois; Lorthiois, Audrey; Leroux-Roels, Geert; Meuleman, Philip; Hermsen, Cornelius C; Mazier, Dominique; Hoffman, Stephen L; Janse, Chris J; Khan, Shahid M; Sauerwein, Robert W

    2014-01-01

    A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. In this study, we present data on safety and protective efficacy using sporozoites with deletions of two genes, that is the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, PbΔb9ΔslarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high-level protection. The human PfΔb9ΔslarpGAP generated without drug resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a PfΔb9ΔslarpSPZ vaccine. PMID:25407681

  4. Porcine epidemic diarrhea: a review of current epidemiology and available vaccines

    PubMed Central

    Song, Daesub; Moon, Hyoungjoon

    2015-01-01

    Porcine epidemic diarrhea virus (PEDV), an Alphacoronavirus in the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. PEDV can also cause diarrhea, agalactia, and abnormal reproductive cycles in pregnant sows. Although PEDV was first identified in Europe, it has resulted in significant economic losses in many Asian swine-raising countries, including Korea, China, Japan, Vietnam, and the Philippines. However, from April 2013 to the present, major outbreaks of PEDV have been reported in the United States, Canada, and Mexico. Moreover, intercontinental transmission of PEDV has increased mortality rates in seronegative neonatal piglets, resulting in 10% loss of the US pig population. The emergence and re-emergence of PEDV indicates that the virus is able to evade current vaccine strategies. Continuous emergence of multiple mutant strains from several regions has aggravated porcine epidemic diarrhea endemic conditions and highlighted the need for new vaccines based on the current circulating PEDV. Epidemic PEDV strains tend to be more pathogenic and cause increased death in pigs, thereby causing substantial financial losses for swine producers. In this review, we described the epidemiology of PEDV in several countries and present molecular characterization of current strains. We also discuss PEDV vaccines and related issues. PMID:26273575

  5. Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario

    PubMed Central

    Rodriguez, Pedro C; Sanchez, Belinda

    2013-01-01

    This review is aimed to focus on NSCLC as an emerging and promising model for active immunotherapy and the challenges for its inclusion in the current clinical scenario. Cancer vaccines for NSCLC have been focused as a therapeutic option based on the identification of a tumor hallmark and the active immunization with the related molecules that triggers cellular and/or humoral responses that consequently destroy or delay the rate of malignant progression. This therapeutic intervention in an established disease state has been aimed to impact into prolonging patient´s survival with ethically accepted quality of life. Understanding of relationship between structure and function in cancer vaccines is essential to interpret their opportunities to impact into prolonging survival and increasing quality of life in cancer patients. It is widely accepted that the failure of the cancer vaccines in the NSCLC scenario is related with its introduction in the advanced disease stages and poor performance status of the patients due to the combination of the tumor induced immunosuppression with the immune senescence. Despite first, second and emerging third line of onco-specific treatments the life expectancy for NSCLC patients diagnosed at advanced stages is surrounding the 12 months of median survival and in facts the today real circumstances are extremely demanding for the success inclusion of cancer vaccines as therapeutic choice in the clinical scenario. The kinetics of the active immunizations encompasses a sequential cascade of clinical endpoints: starting by the activation of the immune system, followed by the antitumor response and finalizing with the consequential impact on patients’ overall survival. Today this cascade of clinical endpoints is the backbone for active immunization assessment and moreover the concept of cancer vaccines, applied in the NSCLC setting, is just evolving as a complex therapeutic strategy, in which the opportunities for cancer vaccines start

  6. Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine

    PubMed Central

    Davis, N A; Crowe, J E; Pajewski, N M; McKinney, B A

    2010-01-01

    The variation in antibody response to vaccination likely involves small contributions of numerous genetic variants, such as single-nucleotide polymorphisms (SNPs), which interact in gene networks and pathways. To accumulate the bits of genetic information relevant to the phenotype that are distributed throughout the interaction network, we develop a network eigenvector centrality algorithm (SNPrank) that is sensitive to the weak main effects, gene–gene interactions and small higher-order interactions through hub effects. Analogous to Google PageRank, we interpret the algorithm as the simulation of a random SNP surfer (RSS) that accumulates bits of information in the network through a dynamic probabilistic Markov chain. The transition matrix for the RSS is based on a data-driven genetic association interaction network (GAIN), the nodes of which are SNPs weighted by the main-effect strength and edges weighted by the gene–gene interaction strength. We apply SNPrank to a GAIN analysis of a candidate-gene association study on human immune response to smallpox vaccine. SNPrank implicates a SNP in the retinoid X receptor α (RXRA) gene through a network interaction effect on antibody response. This vitamin A- and D-signaling mediator has been previously implicated in human immune responses, although it would be neglected in a standard analysis because its significance is unremarkable outside the context of its network centrality. This work suggests SNPrank to be a powerful method for identifying network effects in genetic association data and reveals a potential vitamin regulation network association with antibody response. PMID:20613780

  7. Establishment of reverse genetics system for infectious bronchitis virus attenuated vaccine strain H120.

    PubMed

    Zhou, Ying Shun; Zhang, Yi; Wang, Hong Ning; Fan, Wen Qiao; Yang, Xin; Zhang, An Yun; Zeng, Fan Ya; Zhang, Zhi Kun; Cao, Hai Peng; Zeng, Cheng

    2013-02-22

    Infectious bronchitis virus (IBV) strain H120 was successfully rescued as infectious clone by reverse genetics. Thirteen 1.5-2.8 kb fragments contiguously spanning the virus genome were amplified and cloned into pMD19-T. Transcription grade complete length cDNA was acquired by a modified "No See'm" ligation strategy, which employed restriction enzyme Bsa I and BsmB I and ligated more than two fragments in one T4 ligase reaction. The full-length genomic cDNA was transcribed and its transcript was transfected by electroporation into BHK-21 together with the transcript of nucleocapsid gene. At 48 h post transfection, the medium to culture the transfected BHK-21 cells was harvested and inoculated into 10-days old SPF embryonated chicken eggs (ECE) to replicate the rescued virus. After passage of the virus in ECE five times, the rescued H120 virus (R-H120) was successfully recovered. R-H120 was subsequently identified to possess the introduced silent mutation site in its genome. Some biological characteristics of R-H120 such as growth curve, EID50 and HA titers, were tested and all of them were very similar to its parent strain H120. In addition, both R-H120 and H120 induced a comparable titer of HA inhibition (HI) antibody in immunized chickens and also provided up to 85% of immune protection to the chickens that were challenged with Mass41 IBV strain. The present study demonstrated that construction of infectious clone from IBV vaccine strain H120 is possible and IBV-H120 can be use as a vaccine vector for the development of novel vaccines through molecular recombination and the modified reverse genetics approach. PMID:22999521

  8. Molecular basis of vaccination.

    PubMed

    Del Giudice, G; Pizza, M; Rappuoli, R

    1998-02-01

    Vaccines represent the most cost-effective means to prevent infectious diseases. Most of the vaccines which are currently available were developed long before the era of molecular biology and biotechnology. They were obtained following empirical approaches leading to the inactivation or to the attenuation of microorganisms, without any knowledge neither of the mechanisms of pathogenesis of the disease they were expected to protect from, nor of the immune responses elicited by the infectious agents or by the vaccine itself. The past two decades have seen an impressive progress in the field of immunology and molecular biology, which have allowed a better understanding of the interactions occurring between microbes and their hosts. This basic knowledge has represented an impetus towards the generation of better vaccines and the development of new vaccines. In this monograph we briefly summarize some of the most important biotechnological approaches that are currently followed in the development of new vaccines, and provide details on an approach to vaccine development: the genetic detoxification of bacterial toxins. Such an approach has been particularly successful in the rational design of a new vaccine against pertussis, which has been shown to be extremely efficacious and safe. It has been applied to the construction of powerful mucosal adjuvants, for administration of vaccines at mucosal surfaces. PMID:9789264

  9. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    PubMed

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. PMID:26362098

  10. IL-17 and IL-22 genetic polymorphisms in HBV vaccine non- and low-responders among healthcare workers

    PubMed Central

    Borzooy, Zohreh; Streinu-Cercel, Adrian; Mirshafiey, Abbass; Khamseh, Azam; Mahmoudie, Masoud Karkhaneh; Navabi, Shadi Sadat; Nosrati, Marjan; Najafi, Zahra; Hosseini, Mostafa; Jazayeri, Seyed Mohammad

    2016-01-01

    Background Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers. Methods We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms. Results The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination. Conclusion These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers. PMID:27019828

  11. Biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.

    PubMed

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen(-/-) in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  12. Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

    PubMed Central

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L.

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen−/− in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  13. Genetic variability of porcine circovirus 2 (PCV2) field isolates from vaccinated and non-vaccinated pig herds in Germany.

    PubMed

    Reiner, Gerald; Hofmeister, Regina; Willems, Hermann

    2015-10-22

    Porcine circovirus 2 (PCV2) is responsible for a wide range of associated diseases (PCVD) affecting swine production worldwide. Highly efficient commercial vaccines induce protective immunity, but PCV2 is still circulating in vaccinated farms. Thus, and because of the viruś high mutation rate, recent findings provide concerns about PCV2 strains capable to escape vaccination. Based on 2156 samples from individual pigs of 315 herds from Germany we describe a high effectivity of vaccination between 2008 and the third quarter of 2011. In this period, virus load dropped continuously and at the end of this period it hardly reached the limit of quantification. Thereafter, virus loads re-increased, although most of the herds were still vaccinated. Sixty-two randomly selected samples from vaccinated (n=28) and non-vaccinated (n=26) herds between 2008 and 2012 were completely sequenced. As compared to the PCV2b reference sequence 259 polymorphisms were detected. Polymorhisms were analysed for associations to vaccination status, genotype (PCV2a/PCV2b), and virus load. PCV2a sequences were significantly repelled by PCV2b. One SNP at position 1182 (g.1182G>T), involved in capsid epitope formation, was significantly associated with the PCV2 genotype (2a/2b). Moreover, this SNP was affected by vaccination, with effects on allele frequencies and viral load, independent from the PCV2 genotype (2a/2b). We conclude that there is indeed evidence for a selectional impact of vaccination on the PCV2 sequence, especially on nucleotides involved in epitope formation. Such variation might be responsible for the observed re-increase of PCV2-loads in samples from the end of 2011 in Germany. PMID:26275852

  14. Protective efficacy of a high-growth reassortant swine H3N2 inactivated vaccine constructed by reverse genetic manipulation.

    PubMed

    Wen, Feng; Ma, Ji-Hong; Yu, Hai; Yang, Fu-Ru; Huang, Meng; Zhou, Yan-Jun; Li, Ze-Jun; Tong, Guang-Zhi

    2014-01-01

    Novel reassortant H3N2 swine influenza viruses (SwIV) with the matrix gene from the 2009 H1N1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the United States, indicating that H3N2 SwIV might be a potential threat to public health. Since southern China is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring H3N2 subtype SwIV infections, and thus limit the possibility of SwIV infection at agricultural fairs. In this study, a high-growth reassortant virus (GD/PR8) was generated by plasmid-based reverse genetics and tested as a candidate inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice by challenging them with another H3N2 SwIV isolate [A/Swine/Heilongjiang/1/05 (H3N2) (HLJ/05)]. Prime and booster inoculation with GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting antibodies and IgG antibodies. Complete protection of mice against H3N2 SwIV was observed, with significantly reduced lung lesion and viral loads in vaccine-inoculated mice relative to mock-vaccinated controls. These results suggest that the GD/PR8 vaccine may serve as a promising candidate for rapid intervention of H3N2 SwIV outbreaks in China. PMID:24675833

  15. Current state and perspectives of truffle genetics and sustainable biotechnology.

    PubMed

    Poma, Anna; Limongi, Tania; Pacioni, Giovanni

    2006-09-01

    Mycorrhizal fungi belonging to the genus Tuber produce, after the establishment of a productive interaction with a plant host, hypogeous fruitbodies of great economic value known as ''truffles''. This review summarizes the state of art on life cycle, genetic, and biotechnological investigations of Tuber spp. The ascocarp formation in truffles is a consequence of the activation of the sexual phase of the biological cycle. The formation of a dikaryotic secondary mycelium and the karyogamy in the ascal cell (followed by meiosis with ascospores formation) have been hypothesized by several authors but some doubts yet arise from the Tuber cycle by considering that a series of abnormalities have been pointed out in respect to other Ascomycetes. It is unclear if binucleated hyphal cells are derived from the fusion of mononucleated cells belonging to mycelia from different mating types or from one only. According to the karyotypes of Tuber melanosporum, Tuber magnatum, and Tuber borchii, the numbers of hyphal chromosomes suggest a chromosome number of eight (2n); these values are in the range of those of several Ascomycetes and observed for Tuber aestivum (2n=10). The importance and growth in interest during the last years in the fungi protoplasts isolation and transformation techniques can be related to current developments in Tuber genetics and biotechnology. T. borchii could be transformed through liposome-mediated delivery of genetic material as mycelial protoplasts isolation and fusion with liposomes has already been established. On the other hand, Agrobacterium-mediated transformation has been successfully established for T. borchii. PMID:16802150

  16. Bordetella bronchiseptica Pneumonia in an Infant and Genetic Comparison of Clinical Isolates with Veterinary Kennel Cough Vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An infant with recurrent episodes of respiratory failure was diagnosed with pertussis based on immunofluorescence testing, but culture revealed macrolide-resistant Bordetella bronchiseptica. Genetic analysis demonstrated that the child was not infected with a kennel cough vaccine strain, although th...

  17. Engineering of genetically detoxified pertussis toxin analogs for development of a recombinant whooping cough vaccine.

    PubMed Central

    Loosmore, S M; Zealey, G R; Boux, H A; Cockle, S A; Radika, K; Fahim, R E; Zobrist, G J; Yacoob, R K; Chong, P C; Yao, F L

    1990-01-01

    Pertussis toxin (PT) is an important protective antigen in vaccines against whooping cough, and a genetically detoxified PT analog is the preferred form of the immunogen. Several amino acids of the S1 subunit were identified as functionally critical residues by site-directed mutagenesis, specifically, those at positions 9, 13, 26, 35, 41, 58, and 129. Eighty-three mutated PT operons were introduced into Bordetella parapertussis, and the resultant toxin analogs were screened for expression levels, enzymatic activity, residual toxicity, and antigenicity. While more than half of the mutants were found to be poorly secreted or assembled, the rest were fully assembled and most were highly detoxified. Single mutations resulted in up to a 1,000-fold reduction in both toxic and enzymatic activities, while PT analogs with multiple mutations (Lys-9 Gly-129, Glu-58 Gly-129, and Lys-9 Glu-58 Gly-129) were 10(6)-fold detoxified. Operons coding for stable and nontoxic mutants shown to express a critical immunodominant protective epitope were returned to the chromosome of Bordetella pertussis by allelic exchange. In vivo analysis of the toxin analogs showed a dramatic reduction in histamine sensitization and lymphocytosis-promoting activities, paralleling the reduction in toxic activities. All mutants were protective in an intracerebral challenge test, and the Lys-9 Gly-129 analog was found to be significantly more immunogenic than the toxoid. PT analogs such as those described represent suitable components for the design of a recombinant whooping cough vaccine. Images PMID:2228237

  18. In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.

    PubMed

    Kumar, Hirdesh; Frischknecht, Friedrich; Mair, Gunnar R; Gomes, James

    2015-12-01

    Genetically attenuated parasites (GAPs) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. The genes targeted for deletion were often identified by trial and error. Here we present a systematic gene - protein and transcript - expression analyses of several Plasmodium species with the aim to identify candidate genes for the generation of novel GAPs. With a lack of liver stage expression data for human malaria parasites, we used data available for liver stage development of Plasmodium yoelii, a rodent malaria model, to identify proteins expressed in the liver stage but absent from blood stage parasites. An orthology-based search was then employed to identify orthologous proteins in the human malaria parasite Plasmodium falciparum resulting in a total of 310 genes expressed in the liver stage but lacking evidence of protein expression in blood stage parasites. Among these 310 possible GAP candidates, we further studied Plasmodium liver stage proteins by phyletic distribution and functional domain analyses and shortlisted twenty GAP-candidates; these are: fabB/F, fabI, arp, 3 genes encoding subunits of the PDH complex, dnaJ, urm1, rS5, ancp, mcp, arh, gk, lisp2, valS, palm, and four conserved Plasmodium proteins of unknown function. Parasites lacking one or several of these genes might yield new attenuated malaria parasites for experimental vaccination studies. PMID:26348884

  19. In vitro assessments of the genetic stability of a live recombinant human adenovirus vaccine against rabies.

    PubMed Central

    Lutze-Wallace, C; Sapp, T; Sidhu, M; Wandeler, A

    1995-01-01

    The genetic stability of a live human adenovirus 5: rabies glycoprotein recombinant vaccine has been assessed upon 20 serial passages in a permissive cell line of human origin. Restriction endonuclease analysis and the polymerase chain reaction were used to examine the integrity of the expression cassette for the rabies glycoprotein and the viral vector at the site of insertion of the cassette. It was found that the restriction endonuclease profile was identical for each sample assayed. A more detailed analysis of the expression cassette following amplification by the polymerase chain reaction revealed no changes in the size and number of fragments originating from the coding sequence for the glycoprotein nor the signals controlling the expression of the protein product. The amplified product obtained from the 10th and 20th passages was subjected to nucleotide sequencing. Additionally, 20 plaques isolated from the 20th passage of the virus expressed the rabies glycoprotein as demonstrated by fluorescent antibody staining with glycoprotein specific monoclonal antibodies. These results suggest that the recombinant vaccine maintains the integrity of the heterologous sequences upon passage in tissue culture. Images Fig. 1. Fig. 2. PMID:7648530

  20. Vaccination With a UV-Irradiated Genetically Attenuated Mutant of Staphylococcus aureus Provides Protection Against Subsequent Systemic Infection

    PubMed Central

    Burnside, Kellie; Lembo, Annalisa; Harrell, Maria Isabel; Klein, Jessica Abbey; Lopez-Guisa, Jesus; Siegesmund, Amy M.; Torgerson, Troy R.; Oukka, Mohamed; Molina, Douglas M.; Rajagopal, Lakshmi

    2012-01-01

    Staphylococcus aureus are gram-positive bacteria that cause clinically significant infections in humans. Severe S. aureus infections are particularly problematic in hospitalized patients and reoccur despite therapeutic measures. The absence of natural protective immune responses and the lack of high-throughput approaches to identify S. aureus antigens have imposed constraints in the development of effective vaccines. Here, we showed that vaccination with the genetically attenuated S. aureus mutant, inactivated using UV irradiation rather than heat, significantly increased survival and diminished bacterial burden and kidney abscesses when mice were challenged with virulent methicillin-sensitive or methicillin-resistant S. aureus. Protection conferred by immunization could be transferred to the naive host and was not observed in B-cell–deficient mice. Using a novel S. aureus whole-proteome microarray, we show that immunoglobulin G antibody responses to 83 proteins were observed in the immunized mice. These results suggest that protection against S. aureus infections requires antibody responses to the wide repertoire of antigens/virulence factors. Vaccination using UV-irradiated genetically attenuated S. aureus induces humoral immunity and provides a vaccine strategy for pathogens that fail to induce protective immunity. We also describe a novel, high-throughput technology to easily identify S. aureus antigens for vaccine development. PMID:22966130

  1. Invited review: Current state of genetic improvement in dairy sheep.

    PubMed

    Carta, A; Casu, Sara; Salaris, S

    2009-12-01

    Dairy sheep have been farmed traditionally in the Mediterranean basin in southern Europe, central Europe, eastern Europe, and in Near East countries. Currently, dairy sheep farming systems vary from extensive to intensive according to the economic relevance of the production chain and the specific environment and breed. Modern breeding programs were conceived in the 1960s. The most efficient selection scheme for local dairy sheep breeds is based on pyramidal management of the population with the breeders of nucleus flocks at the top, where pedigree and official milk recording, artificial insemination, controlled natural mating, and breeding value estimation are carried out to generate genetic progress. The genetic progress is then transferred to the commercial flocks through artificial insemination or natural-mating rams. Increasing milk yield is still the most profitable breeding objective for several breeds. Almost all milk is used for cheese production and, consequently, milk content traits are very important. Moreover, other traits are gaining interest for selection: machine milking ability and udder morphology, resistance to diseases (mastitis, internal parasites, scrapie), and traits related to the nutritional value of milk (fatty acid composition). Current breeding programs based on the traditional quantitative approach have achieved appreciable genetic gains for milk yield. In many cases, further selection goals such as milk composition, udder morphology, somatic cell count, and scrapie resistance have been implemented. However, the possibility of including other traits of selective interest is limited by high recording costs. Also, the organizational effort needed to apply the traditional quantitative approach limits the diffusion of current selection programs outside the European Mediterranean area. In this context, the application of selection schemes assisted by molecular information, to improve either traditional dairy traits or traits costly to record

  2. CD226 as a genetic adjuvant to enhance immune efficacy induced by Ag85A DNA vaccination.

    PubMed

    Li, Yan; Yang, Fangli; Zhu, Junfeng; Sang, Lixuan; Han, Xue; Wang, Danan; Shan, Fengping; Li, Shengjun; Sun, Xun; Lu, Changlong

    2015-03-01

    Antigen-85A (Ag85A) is one of the major proteins secreted by Mycobacterium tuberculosis. Many studies on animal models have shown that vaccination with the recombinant Ag85A-DNA or Ag85A protein induces powerful immune response. However, these vaccines cannot generate sufficient protective immunity in the systemic compartment. CD226, a member of the immunoglobulin superfamily, is expressed in the majority of NK cells, T cells, monocytes, and platelets, and can be served as a co-stimulator that contributes to multiple innate and adaptive responses. However, there has been no study where either CD226 protein or DNA has been used as an adjuvant for vaccine development. The aim of this study was to develop a novel Ag85A DNA vaccine with CD226 as the genetic adjuvant to increase the immune efficacy induced by Ag85A. Oral vaccination with pcDNA3.1-Ag85A-CD226 DNA induced potent immune responses in mice. CD226 was an effective genetic adjuvant that improved the immune efficacy induced by Ag85A and enhanced the activity of cytotoxic T lymphocytes (CTL) and NK cells in mice. Th1 dominant cytokines (i.e. IL-2, IFN-γ and TNF-α), cellular immunity (i.e. CD4(+)IFN-γ(+)T cells and CD8(+)IFN-γ(+)T cells in splenocytes) and MLNs were also significantly elevated by pcDNA3.1-Ag85A-CD226 DNA vaccination. Our results suggest that CD226 is an effective adjuvant to enhance the immune efficacy induced by Ag85A. Our findings provide a new strategy for the development of a DNA vaccine co-expressing Ag85A and CD226. PMID:25582686

  3. Development of a tailored vaccine against challenge with very virulent infectious bursal disease virus of chickens using reverse genetics.

    PubMed

    Gao, Li; Qi, Xiaole; Li, Kai; Gao, Honglei; Gao, Yulong; Qin, Liting; Wang, Yongqiang; Wang, Xiaomei

    2011-07-26

    Due to the problems associated with traditional methods for infectious bursal disease virus (IBDV) vaccine development and the pressure of evolution and variation of very virulent strains, it is urgent to develop IBDV vaccine rapidly with novel approaches. Using reverse genetics, the aim of this study was to generate a tailored vaccine strain (rGtHLJVP2) with its VP2 gene similar to very virulent IBDV (vvIBDV) to prevent the prevalence of IBDV. Characteristics of rGtHLJVP2 were evaluated in both cell culture and SPF chickens. rGtHLJVP2 replicated well as its parental strain Gt in vitro and in vivo. Immunization of SPF chickens with rGtHLJVP2 resulted in comparable antibody titers against IBDV as that of the medium virulent live vaccine B87, which was significant higher than that of attenuated vaccine Gt. Challenge studies with 10(4)ELD(50) of prevalent homogeneous or heterogeneous vvIBDV revealed complete (100%) protection in the groups immunized with rGtHLJVP2. No significant clinical and pathological lesions were observed in chickens immunized with rGtHLJVP2. Our data demonstrated that rGtHLJVP2 could be used as a novel vaccine candidate for prevention against vvIBDV. PMID:21658423

  4. Cyanobactins from Cyanobacteria: Current Genetic and Chemical State of Knowledge

    PubMed Central

    Martins, Joana; Vasconcelos, Vitor

    2015-01-01

    Cyanobacteria are considered to be one of the most promising sources of new, natural products. Apart from non-ribosomal peptides and polyketides, ribosomally synthesized and post-translationally modified peptides (RiPPs) are one of the leading groups of bioactive compounds produced by cyanobacteria. Among these, cyanobactins have sparked attention due to their interesting bioactivities and for their potential to be prospective candidates in the development of drugs. It is assumed that the primary source of cyanobactins is cyanobacteria, although these compounds have also been isolated from marine animals such as ascidians, sponges and mollusks. The aim of this review is to update the current knowledge of cyanobactins, recognized as being produced by cyanobacteria, and to emphasize their genetic clusters and chemical structures as well as their bioactivities, ecological roles and biotechnological potential. PMID:26580631

  5. Cyanobactins from Cyanobacteria: Current Genetic and Chemical State of Knowledge.

    PubMed

    Martins, Joana; Vasconcelos, Vitor

    2015-11-01

    Cyanobacteria are considered to be one of the most promising sources of new, natural products. Apart from non-ribosomal peptides and polyketides, ribosomally synthesized and post-translationally modified peptides (RiPPs) are one of the leading groups of bioactive compounds produced by cyanobacteria. Among these, cyanobactins have sparked attention due to their interesting bioactivities and for their potential to be prospective candidates in the development of drugs. It is assumed that the primary source of cyanobactins is cyanobacteria, although these compounds have also been isolated from marine animals such as ascidians, sponges and mollusks. The aim of this review is to update the current knowledge of cyanobactins, recognized as being produced by cyanobacteria, and to emphasize their genetic clusters and chemical structures as well as their bioactivities, ecological roles and biotechnological potential. PMID:26580631

  6. Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines.

    PubMed

    Miguel, A; Herrero, M J; Sendra, L; Botella, R; Algás, R; Sánchez, M; Aliño, S F

    2013-10-01

    Genetically modified cells have been shown to be one of the most effective cancer vaccine strategies. An evaluation is made of the efficacy of both preventive and therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and irradiated B16 tumor cells expressing granulocyte and macrophage colony-stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was transplanted by the injection of wild-type B16 cells. Tumor growth and survival were measured to evaluate the efficacy of vaccination. Specific humoral response and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and IgG2a subtypes against tumor membrane proteins of B16 cells. In preventive vaccination, all treated groups showed delayed tumor growth. In addition, the group vaccinated to express only GM-CSF achieved 100% animal survival (P<0.005). Vaccination with GM-CSF+IL-12-producing B16 cells yielded lesser results (60% survival, P<0.005). Furthermore, all surviving animals remained disease-free after second tumor implantation 1 year later. The therapeutic vaccination strategies resulted in significantly delayed tumor growth, mainly using B16 cells producing GM-CSF+IL-12 cytokines, with 70% tumor growth inhibition (P<0.001)-although none of the animals reached overall survival. The results obtained suggest that the GM-CSF+IL-12 combination only increases the efficacy of therapeutic vaccines. No differences in classical regulatory T cells were found among the different groups. PMID:23969885

  7. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

    PubMed

    Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

    2015-01-01

    Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine. PMID:26716832

  8. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System

    PubMed Central

    Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

    2015-01-01

    Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine. PMID:26716832

  9. Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough.

    PubMed Central

    Nencioni, L; Pizza, M; Bugnoli, M; De Magistris, T; Di Tommaso, A; Giovannoni, F; Manetti, R; Marsili, I; Matteucci, G; Nucci, D

    1990-01-01

    the introduction of two amino acid substitutions within the enzymatically active subunit S1 of pertussis toxin (PT) abolishes its ADP-ribosyltransferase activity and toxicity on CHO cells (Pizza et al., Science 246:497-500, 1989). These genetically inactivated molecules are also devoid of other in vivo adverse reactions typical of PT, such as induction of leukocytosis, potentiation of anaphylaxis, stimulation of insulin secretion, and histamine sensitivity. However, the mutant PT molecules are indistinguishable from wild-type PT in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and maintain all the physical and chemical properties of PT, including affinity for toxin-neutralizing poly- and monoclonal antibodies. Either alone or stabilized with formaldehyde, PT mutants are able to induce high levels of neutralizing antibodies and to protect mice in a dose-dependent fashion against intracerebral challenge with virulent B. pertussis. These results clearly show that these genetically inactivated PT molecules are nontoxic but still immunogenic and justify their development as a component of a new, safer acellular vaccine against whooping cough. Images PMID:2323818

  10. Genetic analysis of attenuation markers of cold-adapted X-31 influenza live vaccine donor strain.

    PubMed

    Jang, Yo Han; Jung, Eun-Ju; Lee, Kwang-Hee; Byun, Young Ho; Yang, Seung Won; Seong, Baik Lin

    2016-03-01

    Cold-adapted live attenuated influenza vaccines (CAIVs) have been considered as a safe prophylactic measure to prevent influenza virus infections. The safety of a CAIV depends largely on genetic markers that confer specific attenuation phenotypes. Previous studies with other CAIVs reported that polymerase genes were primarily responsible for the attenuation. Here, we analyzed the genetic mutations and their phenotypic contribution in the X-31 ca strain, a recently developed alternative CAIV donor strain. During the cold-adaptation of its parental X-31 virus, various numbers of sequence changes were accumulated in all six internal genes. Phenotypic analysis with single-gene and multiple-gene reassortant viruses suggests that NP gene makes the largest contribution to the cold-adapted (ca) and temperature-sensitive (ts) characters, while the remaining other internal genes also impart attenuation characters with varying degrees. A balanced contribution of all internal genes to the attenuation suggests that X-31 ca could serve as an ideal master donor strain for CAIVs preventing influenza epidemics and pandemics. PMID:26851733

  11. Current polio global eradication and control policy options: perspectives from modeling and prerequisites for oral poliovirus vaccine cessation.

    PubMed

    Thompson, Kimberly M; Tebbens, Radboud J Duintjer

    2012-04-01

    As the Global Polio Eradication Initiative progresses toward the eradication of wild polioviruses, national and global health leaders must still actively consider options for managing poliovirus risks, including risks associated with using oral poliovirus vaccine. Oral poliovirus vaccine continues to represent a highly effective tool, but its use causes noticeable, rare cases of vaccine-associated paralytic polio and with low coverage it can evolve to become circulating vaccine-derived polioviruse that causes outbreaks. National leaders face a wide range of options, but their choices depend in part on global policies. This article explores the current set of global options for poliovirus eradication or control, discusses constraints and prerequisites for their implementation and offers some insights based on dynamic modeling to inform discussions and frame future economic analyses. PMID:22551030

  12. Experimental rabies vaccines for humans

    PubMed Central

    McGettigan, James P

    2011-01-01

    Rabies remains a global public health threat that kills more than 55,000 people per year. Rabies disproportionately affects children and, therefore, is ranked the seventh most important infectious disease due to years lost. Prevention of human rabies is accomplished by controlling rabies in domestic and wild animals, including the use of vaccination programs. The usefulness of human rabies vaccines is hampered by high cost, complicated vaccination regimens and lack of compliance, especially in areas of Africa and Asia where human rabies infections are endemic. A single-dose vaccine would greatly benefit efforts to combat this global health threat. However, a single-dose vaccine based on current inactivated vaccines does not appear feasible and other approaches are needed. Technology has advanced since modern human rabies vaccines were developed over 40 years ago. In addition, our understanding of immunological principles that influence the outcome of vaccination has increased. This article describes the current status of inactivated rabies virus vaccines and recent developments arising from the use of reverse genetics technologies designed to develop replication-deficient or single-cycle live rabies virus-based vectors for use as a single-dose rabies vaccine for humans. PMID:20923268

  13. Experimental rabies vaccines for humans.

    PubMed

    McGettigan, James P

    2010-10-01

    Rabies remains a global public health threat that kills more than 55,000 people per year. Rabies disproportionately affects children and, therefore, is ranked the seventh most important infectious disease due to years lost. Prevention of human rabies is accomplished by controlling rabies in domestic and wild animals, including the use of vaccination programs. The usefulness of human rabies vaccines is hampered by high cost, complicated vaccination regimens and lack of compliance, especially in areas of Africa and Asia where human rabies infections are endemic. A single-dose vaccine would greatly benefit efforts to combat this global health threat. However, a single-dose vaccine based on current inactivated vaccines does not appear feasible and other approaches are needed. Technology has advanced since modern human rabies vaccines were developed over 40 years ago. In addition, our understanding of immunological principles that influence the outcome of vaccination has increased. This article describes the current status of inactivated rabies virus vaccines and recent developments arising from the use of reverse genetics technologies designed to develop replication-deficient or single-cycle live rabies virus-based vectors for use as a single-dose rabies vaccine for humans. PMID:20923268

  14. Comparative genomics of BCG vaccines.

    PubMed

    Behr, M A

    2001-01-01

    Bacille Calmette-Guérin (BCG) vaccines have been given to more people than any other vaccine. They have also probably resulted in as much controversy as any other vaccine. In clinical trials, the efficacy of BCG vaccination against pulmonary TB has been widely variable. At the same time, a number of investigators have observed phenotypic differences between BCG daughter strains, raising the possibility that differences between BCG products may in some way translate into different outcomes. With recent genomic analysis of BCG strains, it has become possible to piece together the molecular events that have resulted in current BCG vaccines. Between the derivation of BCG in 1921 and the lyophilization of BCG Pasteur 1173 in 1961, there have been at least seven genetic events, including deletions, duplications and a single nucleotide polymorphism. The phenotypic relevance of these changes in BCG vaccines remains to be explored. PMID:11463238

  15. [Efficacy and safety of vaccines against tuberculosis in the relation to genetic variability of Mycobacterium bovis BCG strains].

    PubMed

    Prygiel, Marta; Janaszek-Seydlitz, Wiesława; Bucholc, Bozena

    2011-01-01

    All vaccines against tuberculosis used actually over the world contain Mycobacterium bovis BCG strains (Bacillus Calmette-Guerin) as active substance. Strain BCG, that was obtained in 1921 by Calmette and Guerin after 13 years ofpassaging on the potato-glicerol medium with addition of bile, was distributed to many laboratories for vaccine production. The repeated passages of M. bovis BCG strain in different culture conditions caused the numerous mutations and formation of many BCG substrains that differed according to efficacy and safety. The review of many publications related to genetic differences between BCG substrains was performed for identify the genes responsible for their virulence and protective characteristics. Possibility of development of new generation vaccines against tuberculosis is discussed. PMID:22390050

  16. Current Advances in the Identification and Characterization of Putative Drug and Vaccine Targets in the Bacterial Genomes.

    PubMed

    Shahbaaz, Mohd; Bisetty, Krishna; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2016-01-01

    The development in sequencing technologies over the past few decades have increased the pace of decoding genetic and functional information present in the genomes of pathogenic microorganisms. The knowledge obtained through sequencing projects facilitated the identification of genes that codes for virulence factors. A major portion of genomes of pathogenic of bacteria contains genes which are classified as "hypothetical or uncharacterized". Due to unavailability of precise information about the functionality of these genes, the pathogenic mechanisms utilized by varieties of microorganisms are not fully understood. This respective class of proteins draws a significant interest of pharmaceutical research as they have potential to provide new clues regarding the development of novel therapeutics particularly against the multidrug resistant strains of bacteria. The in silico identification of putative drug and vaccine targets in the set of uncharacterized proteins through comparative and subtractive genome analyses facilitates the increase usability and efficiency of the present drugs. The functional annotation of these characterized target proteins can uncover varieties of biochemical pathways important for the survival and pathogenesis of bacteria. This review focuses on the current protocols available for identification and functional annotations of these uncharacterized potential therapeutic targets. PMID:26303422

  17. Rubella: Current Status, Diagnosis, Outbreak Control, and Use of Rubella Vaccine in Females of Childbearing Age.

    ERIC Educational Resources Information Center

    Preblud, Stephen R.

    1984-01-01

    Widespread rubella vaccination of young children with a secondary emphasis on vaccinating susceptible adolescents and young adults has prevented epidemics of rubella and congenital rubella syndrome. Benefits of ensuring high immunity levels in college students, quick response to disease outbreak, and safety and efficacy of rubella vaccine in this…

  18. Current status and uptake of influenza vaccination over time among senior adults in the United States.

    PubMed

    Lu, Peng-Jun; O'Halloran, Alissa; Ding, Helen; Greby, Stacie M; Williams, Walter W

    2015-01-01

    Influenza is a major cause of morbidity and mortality among older adults in the United States, who may also have chronic medical conditions that place them at high risk for complications from influenza. The U.S. Public Health Service recommended influenza vaccination of adults ≥ 65 y and chronically ill persons since 1961 and beginning with the 2010-11 influenza season, the Advisory Committee on Immunization Practices (ACIP) has expanded its recommendation to vaccinate all persons 6 months of age and older. Medicare coverage for influenza vaccination began in 1993. However, despite the presence of a safe and effective vaccine, long-standing recommendations on vaccination, and federal financial support for vaccination, vaccination levels among adults ≥ 65 y are not optimal. Studies have shown that influenza vaccination coverage among U.S. adults ≥ 65 y steadily increased from 30.1% in 1989 to 64.2% in 1997, but plateaued near 65% from 1998 to 2013. Increasing influenza vaccination coverage among older adults in the United States will require more cooperation among health-care providers, professional organizations, vaccine manufacturers, and public health departments to raise public awareness about the benefits of influenza vaccination and to ensure continued administration of vaccinations throughout the influenza season. PMID:26697974

  19. Preparation of genetically engineered A/H5N1 and A/H7N1 pandemic vaccine viruses by reverse genetics in a mixture of Vero and chicken embryo cells

    PubMed Central

    Legastelois, Isabelle; Garcia‐Sastre, Adolfo; Palese, Peter; Tumpey, Terrence M.; Maines, Taronna R.; Katz, Jacqueline M.; Vogel, Frederick R.; Moste, Catherine

    2007-01-01

    Background  In case of influenza pandemic, a robust, easy and clean technique to prepare reassortants would be necessary. Objectives  Using reverse genetics, we prepared two vaccine reassortants (A/H5N1 × PR8 and A/H7N1 × PR8) exhibiting the envelope glycoproteins from non‐pathogenic avian viruses, A/Turkey/Wisconsin/68 (A/H5N9) and A/Rhea/New Caledonia/39482/93 (A/H7N1) and the internal proteins of the attenuated human virus A/Puerto Rico/8/34 (H1N1). Methods  The transfection was accomplished using a mixture of Vero and chicken embryo cells both of which are currently being used for vaccine manufacturing. Results  This process was reproducible, resulting in consistent recovery of influenza viruses in 6 days. Because it is mainly the A/H5N1 strain that has recently crossed the human barrier, it is the A/PR8 × A/H5N1 reassortant (RG5) that was further amplified, either in embryonated hen eggs or Vero cells, to produce vaccine pre‐master seed stocks that met quality control specifications. Safety testing in chickens and ferrets was performed to assess the non‐virulence of the reassortant, and finally analysis using chicken and ferret sera immunized with the RG5 virus showed that the vaccine candidate elicited an antibody response cross‐reactive with the Hong Kong 1997 and 2003 H5N1 strains but not the Vietnam/2004 viruses. Conclusions  The seeds obtained could be used as part of a pandemic vaccine strain ‘library’ available in case of propagation in humans of a new highly pathogenic avian strain. PMID:19453414

  20. Molecular mechanisms of paraptosis induction: implications for a non-genetically modified tumor vaccine.

    PubMed

    Hoa, Neil; Myers, Michael P; Douglass, Thomas G; Zhang, Jian Gang; Delgado, Christina; Driggers, Lara; Callahan, Linda L; VanDeusen, Gerald; Pham, Jimmy T H; Bhakta, Nirav; Ge, Lisheng; Jadus, Martin R

    2009-01-01

    Paraptosis is the programmed cell death pathway that leads to cellular necrosis. Previously, rodent and human monocytes/macrophages killed glioma cells bearing the membrane macrophage colony stimulating factor (mM-CSF) through paraptosis, but the molecular mechanism of this killing process was never identified. We have demonstrated that paraptosis of rat T9 glioma cells can be initiated through a large potassium channel (BK)-dependent process initiated by reactive oxygen species. Macrophage mediated cytotoxicity upon the mM-CSF expressing T9-C2 cells was not prevented by the addition of the caspase inhibitor, zVAD-fmk. By a combination of fluorescent confocal and electron microscopy, flow cytometry, electrophysiology, pharmacology, and genetic knock-down approaches, we demonstrated that these ion channels control cellular swelling and vacuolization of rat T9 glioma cells. Cell lysis is preceded by a depletion of intracellular ATP. Six-hour exposure to BK channel activation caused T9 cells to over express heat shock proteins (Hsp 60, 70, 90 and gp96). This same treatment forced HMGB1 translocation from the nuclear region to the periphery. These last molecules are "danger signals" that can stimulate immune responses. Similar inductions of mitochondrial swelling and increased Hsp70 and 90 expressions by BK channel activation were observed with the non-immunogenic F98 glioma cells. Rats injected with T9 cells which were killed by prolonged BK channel activation developed immunity against the T9 cells, while the injection of x-irradiated apoptotic T9 cells failed to produce the vaccinating effect. These results are the first to show that glioma cellular death induced by prolonged BK channel activation improves tumor immunogenicity; this treatment reproduces the vaccinating effects of mM-CSF transduced cells. Elucidation of strategies as described in this study may prove quite valuable in the development of clinical immunotherapy against cancer. PMID:19247476

  1. Protective immune response against Toxoplasma gondii elicited by a recombinant DNA vaccine with a novel genetic adjuvant.

    PubMed

    Zhou, Huaiyu; Min, Juan; Zhao, Qunli; Gu, Qinmin; Cong, Hua; Li, Ying; He, Shenyi

    2012-02-27

    Previous immunological studies from our laboratory have demonstrated the potential role of Toxoplasma gondii antigens SAG1 and GRA2 as vaccine candidates. To further evaluate the vaccine's effects, a series of recombinant DNA vaccines pVAX1-SAG1, pVAX1-GRA2 and pVAX1-SAG1-GRA2, termed pSAG1, pGRA2 and pSAG1-GRA2, respectively, were constructed. A plasmid pVAX1-S/PreS2, termed pSPreS2 encoding hepatitis B virus (HBV) surface antigen (HBsAg) S and PreS2 as a novel genetic adjuvant, was also constructed. The expression abilities of those DNA plasmids were examined in HFF cells by Western blotting. Then BALB/c mice were intramuscularly immunized with DNA plasmids and followed by challenging with the highly virulent T. gondii RH strain. The results demonstrated that the recombinant DNA vaccine pSAG1-GRA2 was capable of eliciting high levels of antibodies, a Th1 type of immune response with significant production of IFN-γ and low levels of IL-4 or IL-10 in BALB/c mice, and partial protection against the acute phase of toxoplasmosis as compared to pSAG1, pGRA2 and controls. In addition, the adjuvant pSPreS2 formulated with DNA vaccine induced a Th1 type of immune response and therefore might be a novel genetic adjuvant to DNA vaccine for further investigation. PMID:22240340

  2. Jabs and barbs: ways to address misleading vaccination and immunisation information using currently available strategies.

    PubMed

    Wardle, Jon; Stewart, Cameron; Parker, Malcolm

    2013-09-01

    Misleading vaccination information undermines confidence in vaccination and may lead to reductions in the effectiveness of vaccination programs. A number of regulatory techniques can be employed to challenge the spread of false information, including health care complaints, therapeutic goods laws, consumer protection laws and professional discipline. This article examines three case studies involving the publication of anti-vaccination information by non-professionally aligned organisations, by non-registered health professionals, and by registered health professionals under the National Law. The article examines the effectiveness of different regulatory responses and makes suggestions for future strategies to deal with the publication of demonstrably false information regarding vaccination. PMID:24218789

  3. Genetic polymorphisms of CXCR5 and CXCL13 are associated with non-responsiveness to the hepatitis B vaccine.

    PubMed

    Duan, Zhaojun; Chen, Xiangmei; Liang, Zhenglun; Zeng, Ying; Zhu, Fengcai; Long, Lu; McCrae, Malcolm A; Zhuang, Hui; Shen, Tao; Lu, Fengmin

    2014-09-15

    A cohort based study has been undertaken to investigate the possible association of genetic polymorphisms in genes functionally related to follicular T helper (TfH) cells with non-responsiveness to hepatitis B virus (HBV) vaccination. A total of 24 single nucleotide polymorphisms (SNPs) in 6 TfH related genes (CXCR5, ICOS, CXCL13, IL-21, BCL6 and CD40L) were investigated in 20 non-responders and 45 responders to HBV vaccination. Genetic association analysis revealed that three SNPs (rs497916, rs3922, rs676925) in CXCR5 and one SNP (rs355687) in CXCL13 were associated with hepatitis B vaccine efficacy. In addition, significantly unbalanced distributions of two haplotypes, defined by three SNPs (rs497916, rs3922, rs676925) within CXCR5, were also seen between non-responders and responders. Furthermore, we demonstrated that the rs3922 "GG" genotype was associated with higher levels of CXCR5 than the "AG" and "AA" genotype in a group of healthy volunteers. A dual luciferase report assay was used to confirm that the "G" allele in rs3922 may lead to higher gene expression than the "A" allele, implicating that rs3922 might be a functional SNP affecting CXCR5 expression. These results indicated that polymorphism associated changes in CXCR5 expression in TfH cells may be associated with non-responsiveness to hepatitis B vaccination. PMID:25077417

  4. Bacterial vaccines for fish--an update of the current situation worldwide.

    PubMed

    Håstein, T; Gudding, R; Evensen, O

    2005-01-01

    During the last few years, the use of vaccines for disease prevention in aquaculture has expanded both with regard to the number of fish species and number of microbial diseases. According to the responses to a questionnaire received from 41 countries, vaccination is used in the commercial aquaculture of species like Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus mykiss), sea bass (Dicentrarchus labrax), sea bream (Sparus aurata), barramundi (Lates calcarifer), tilapia (Tilapia spp), turbot (Scophthalmus maximus L.), yellowtail (Seriola quinqueradiata), purplish and gold-striped amberjack (Seriola dumereli), striped jack (Pseudocaranx dentex) and channel catfish (Ictalurus punctatus). The range of bacterial infections for which vaccines are commercially available now comprises classical vibriosis (Listonella anguillarum, Vibrio ordalii), furunculosis (Aeromonas salmonicida subsp. salmonicida), cold-water vibriosis (Vibrio salmonicida), yersiniosis (Yersinia ruckeri), pasteurellosis (Photobacterium damselae supsp. piscicida), edwardsiellosis (Edwardsiella ictaluri), winter ulcer (Moritella viscosa), and streptococcosis/lactococcosis (Streptococcus iniae, Lactococcus garviae). Furthermore, experimental vaccines are used against diseases such as infection with Vibrio harveyi and Photobacterium damsela subsp. damsela in barramundi, piscirickettsiosis and bacterial kidney disease in salmonids, as well as infection with Flexibacter maritimus (now: Tenacibaculum maritimum) in turbot. There was good agreement between the information received from different sources in the same country. Most vaccines are licensed products, but some non-licensed vaccines are also used in commercial fish farms. Most bacterial vaccines are inactivated products and recombinant vaccine technology has so far been used to a very limited extent. Salmonid fish are usually immunised with multivalent vaccines by intraperitoneal injection. In marine fish species vaccination is generally

  5. The Activity of Rabies Vaccines against Genetic Clusters of Rabies Virus Circulating at the Territory of Ukraine

    PubMed Central

    Ivanov, Mykola; Polupan, Ivan; Deryabin, Oleg

    2013-01-01

    Objective To identify the presence of genetic clusters of rabies virus at the territory of Ukraine and to determine the degree of activity of rabies vaccines against these genetic clusters. Introduction To develop and implement an effective program of rabies eradication in Ukraine in 2008 was founded the unique collection of samples of pathological materials confirmed as positive in rabies at the regional veterinary laboratories of Ukraine. The collection is constantly updated and to present moment it includes 1389 samples from all regions of Ukraine, selected from 17 animal species and humans. Methods Identification of the rabies virus in samples of pathological material for their further selection was carried out using the test developed by us which based on RT-PCR with primers complementary to the conservative fragments of the 5’-end of nucleoprotein gene of rabies virus. For the study of the street rabies virus isolates from the collection we use RT-PCR with the primers pair (509, 304) flanking the variable 3’-end part of nucleoprotein gene of the reference strain of rabies virus CVS (fragment in 377 bp). Studies of rabies vaccines activity were carried out with modified method of U.S. National Institutes of Health using rabies virus street isolates of both genetic clusters instead of the Challenge Virus Standard (CVS). All isolates of street rabies virus were inoculated in a dose of 5–50 LD50. The criteria for evaluation of protective activity of rabies vaccine was effective dose (− lg ED50). Results In molecular genetic studies with variant-specific primers we established the presence in Ukraine of two clusters of rabies virus. Clusters I circulates on the right bank of the Dnipro river (the largest water barrier that divides the country into eastern and western side), and cluster II – on the left bank of the Dnieper. The relationship of these variants with the epizootic situation was researched. For this purpose epizootological zoning of Ukraine

  6. Vaccine adjuvants--understanding molecular mechanisms to improve vaccines.

    PubMed

    Egli, Adrian; Santer, Deanna; Barakat, Khaled; Zand, Martin; Levin, Aviad; Vollmer, Madeleine; Weisser, Maja; Khanna, Nina; Kumar, Deepali; Tyrrell, Lorne; Houghton, Michael; Battegay, Manuel; O'Shea, Daire

    2014-01-01

    Infectious pathogens are responsible for high utilisation of healthcare resources globally. Attributable morbidity and mortality remains exceptionally high. Vaccines offer the potential to prime a pathogen-specific immune response and subsequently reduce disease burden. Routine vaccination has fundamentally altered the natural history of many frequently observed and serious infections. Vaccination is also recommended for persons at increased risk of severe vaccine-preventable disease. Many current nonadjuvanted vaccines are poorly effective in the elderly and immunocompromised populations, resulting in nonprotective postvaccine antibody titres, which serve as surrogate markers for protection. The vaccine-induced immune response is influenced by: (i.) vaccine factors i.e., type and composition of the antigen(s), (ii.) host factors i.e., genetic differences in immune-signalling or senescence, and (iii.) external factors such as immunosuppressive drugs or diseases. Adjuvanted vaccines offer the potential to compensate for a lack of stimulation and improve pathogen-specific protection. In this review we use influenza vaccine as a model in a discussion of the different mechanisms of action of the available adjuvants. In addition, we will appraise new approaches using "vaccine-omics" to discover novel types of adjuvants. PMID:24844935

  7. Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: Current status and future direction.

    PubMed

    Renukaradhya, Gourapura J; Meng, Xiang-Jin; Calvert, Jay G; Roof, Michael; Lager, Kelly M

    2015-06-17

    Within a few years of its emergence in the late 1980s, the PRRS virus had spread globally to become the foremost infectious disease concern for the pork industry. Since 1994, modified live-attenuated vaccines against porcine reproductive and respiratory syndrome virus (PRRSV-MLV) have been widely used, but have failed to provide complete protection against emerging and heterologous field strains of the virus. Moreover, like many other MLVs, PRRSV-MLVs have safety concerns including vertical and horizontal transmission of the vaccine virus and several documented incidences of reversion to virulence. Thus, the development of efficacious inactivated vaccines is warranted for the control and eradication of PRRS. Since the early 1990s, researchers have been attempting to develop inactivated PRRSV vaccines, but most of the candidates have failed to elicit protective immunity even against homologous virus challenge. Recent research findings relating to both inactivated and subunit candidate PRRSV vaccines have shown promise, but they need to be pursued further to improve their heterologous efficacy and cost-effectiveness before considering commercialization. In this comprehensive review, we provide information on attempts to develop PRRSV inactivated and subunit vaccines. These includes various virus inactivation strategies, adjuvants, nanoparticle-based vaccine delivery systems, DNA vaccines, and recombinant subunit vaccines produced using baculovirus, plant, and replication-deficient viruses as vector vaccines. Finally, future directions for the development of innovative non-infectious PRRSV vaccines are suggested. Undoubtedly there remains a need for novel PRRSV vaccine strategies targeted to deliver cross-protective, non-infectious vaccines for the control and eradication of PRRS. PMID:25980425

  8. Reverse genetics of Mononegavirales: How they work, new vaccines, and new cancer therapeutics

    PubMed Central

    Pfaller, Christian K.; Cattaneo, Roberto; Schnell, Matthias J.

    2015-01-01

    The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular basis of tissue tropism and pathogenesis. Studies have assessed the relevance for virulence of different receptors and the interactions with cellular proteins governing the innate immune responses. Research has also analyzed the mechanisms of attenuation. Based on these findings, ongoing clinical trials are exploring new live attenuated vaccines and the use of viruses re-engineered as cancer therapeutics. PMID:25702088

  9. Measles virus genetic evolution throughout an imported epidemic outbreak in a highly vaccinated population.

    PubMed

    Muñoz-Alía, Miguel Ángel; Fernández-Muñoz, Rafael; Casasnovas, José María; Porras-Mansilla, Rebeca; Serrano-Pardo, Ángela; Pagán, Israel; Ordobás, María; Ramírez, Rosa; Celma, María Luisa

    2015-01-22

    Measles virus circulates endemically in African and Asian large urban populations, causing outbreaks worldwide in populations with up-to-95% immune protection. We studied the natural genetic variability of genotype B3.1 in a population with 95% vaccine coverage throughout an imported six month measles outbreak. From first pass viral isolates of 47 patients we performed direct sequencing of genomic cDNA. Whilst no variation from index case sequence occurred in the Nucleocapsid gene hyper-variable carboxy end, in the Hemagglutinin gene, main target for neutralizing antibodies, we observed gradual nucleotide divergence from index case along the outbreak (0% to 0.380%, average 0.138%) with the emergence of transient and persistent non-synonymous and synonymous mutations. Little or no variation was observed between the index and last outbreak cases in Phosphoprotein, Nucleocapsid, Matrix and Fusion genes. Most of the H non-synonymous mutations were mapped on the protein surface near antigenic and receptors binding sites. We estimated a MV-Hemagglutinin nucleotide substitution rate of 7.28 × 10-6 substitutions/site/day by a Bayesian phylogenetic analysis. The dN/dS analysis did not suggest significant immune or other selective pressures on the H gene during the outbreak. These results emphasize the usefulness of MV-H sequence analysis in measles epidemiological surveillance and elimination programs, and in detection of potentially emergence of measles virus neutralization-resistant mutants. PMID:25445338

  10. [Development of new vaccines].

    PubMed

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

    Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. PMID:26341041

  11. Overview of currently available Japanese acellular pertussis vaccines and future problems.

    PubMed

    Kamiya, H; Nii, R

    1988-01-01

    Acellular pertussis diphtheria, tetanus vaccine (APDT) was licensed in 1981 in Japan. This vaccine contains pertussis toxin (PT), filamentous hemagglutinin (FHA) and agglutinogen (AGG) as the main protective antigens. The new APDT vaccine produced by each company differs slightly in composition. There are two representative types of vaccine. One vaccine (B type) contains PT and FHA in a ratio of 1 to 1 and the other one (T type) contains PT and FHA in a ratio of 4 to 1 or 9 to 1 and also contains different amounts of AGG. We have been comparing the effectiveness of these two types of vaccine. The adverse reactions of APDT were local reactions such as redness and swelling, with a few febrile cases. No central nervous system adverse reactions were observed. The antibody protective level of this vaccine is also being investigated. After we changed from conventional vaccine to APDT, the frequency of serious adverse reactions was reduced and the number of pertussis infections also gradually decreased. This vaccine should be used for the children world-wide. PMID:3273618

  12. Vaccine adjuvants – Current status and prospects on controlled release adjuvancity

    PubMed Central

    Sivakumar, S.M.; Safhi, Mohammed M.; Kannadasan, M.; Sukumaran, N.

    2011-01-01

    The strategy of World Health Organization is to develop efficient and inexpensive vaccine against various infectious diseases amongst children’s population. Vaccination is considered as the most cost effective health intervention known to public. Since 90 years various substances have been added in vaccine formulation but still alum is considered as the safest adjuvant for human use licensed by United States Food and Drug Administration. MF 59 and ASO4 are the adjuvants were developed recently and approved for human use. Due to poor adjuvancity, conventional vaccines require multiple recall injection at approximately time intervals to attain optimal immune response. For past approximately two decades the vaccine research has been focused towards the alternation of alum type of adjuvant in order to increase the immunogenicity. The development of new vaccines, is more efficacious or easier to deliver, or both have become an area of research that can certainly benefit from controlled release technology. Especially, the conversion of multiple administration vaccine into single administration vaccine may represent an improved advancement towards the betterment of human health care and welfare. Biodegradable polymer microparticles have been evaluated for delivering antigens in native form, sustained release keeping in mind the safety aspects. In this article we review the overall concept of adjuvants in vaccine technology with special focus towards the prospects of controlled release antigens. PMID:23960760

  13. Vaccination Policy in Korean Armed Forces: Current Status and Future Challenge

    PubMed Central

    Yoon, Chang-Gyo; Jeong, Hye Won; Kim, Woo Joo; Cheong, Hee Jin

    2015-01-01

    Infectious diseases have historically resulted in suspended or cancelled military operations. Vaccination for disease prevention is a critical component of the military's force readiness doctrine. Until recently, Korea had not recognized the importance of vaccinating military personnel. However, a 2011 meningococcal disease outbreak at an army recruit training center led to dramatic changes in the paradigm of traditional medical practice in the Korean armed forces. A new vaccination policy was formed by a 2012 Military Healthcare Service Act. Since then, Neisseria meningitidis, hepatitis A, and measles-mumps-rubella vaccines have been routinely administered to all new recruits early in basic training to ensure protection against these diseases. All active-duty soldiers also receive seasonal influenza vaccination annually. Despite quantitative improvements in vaccination policies, several instances of major infectious diseases and adverse vaccine reactions have threatened soldier health. In the future, vaccination policies in the Korean armed forces should be based on epidemiologic data and military medical research for vaccine use and safety management. PMID:25829800

  14. Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus

    PubMed Central

    Gao, Xiaoyan; Li, Minghua; Cui, Shiheng; Li, Xiaolong; Cao, Yuxi; Lei, Wenwen; Lu, Zhi; He, Ying; Wang, Huanyu; Yan, Jinghua; Gao, George Fu; Liang, Guodong

    2016-01-01

    Background The current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1–G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported. Methods/Principal Findings Using in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT90 method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10–1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults. Conclusions/Significance Low levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV. PMID:27139722

  15. Tick-borne Encephalitis Vaccines

    PubMed Central

    Lehrer, Axel T; Holbrook, Michael R.

    2012-01-01

    Tick-borne encephalitis (TBE) is a disease that is found from western Europe across Asia and into Japan. In recent years the incidence rate has been increasing as has the endemic range of the virus. Tick-borne encephalitis is caused by three genetically distinct sutypes of viruses within a single TBE virus (TBEV) serocomplex. These three subtypes consist of Far-eastern subtype TBEV (TBEV-FE), Siberian subtype (TBEV-Sib) and European subtype (TBEV-Eu). Each of these subtypes cause clinically distinct diseases with varying degrees of severity. Development of the first vaccines for TBEV began in the late 1930s shortly after the first isolation of TBEV-FE in Russia. In the 1970s Austria began large scale vaccine production and a nationalized vaccine campaign that significantly reduced the incidence rate of TBE. Currently there are four licensed TBE vaccines, two in Europe and two in Russia. These vaccines are all quite similar formalin-inactivated virus vaccines but the each use a different virus strain for production. Published studies have shown that European vaccines are cross-protective in rodent studies and elicit cross-reactive neutralizing antibody responses in human vaccines. European vaccines have been licensed for a rapid vaccine schedule that could be used in response to a significant outbreak and reasonable neutralizing antibody titers can be achieved after a single dose although a second dose provides nearly complete and long-lasting protection. This review focuses on the current status of licensed TBE vaccines and provides a brief summary of technology currently being developed for new vaccines. PMID:23997980

  16. A current genetic and epigenetic view on human aging mechanisms.

    PubMed

    Ostojić, Sala; Pereza, Nina; Kapović, Miljenko

    2009-06-01

    The process of aging is one of the most complex and intriguing biological phenomenons. Aging is a genetically regulated process in which the organism's maximum lifespan potential is pre-determined, while the rate of aging is influenced by environmental factors and lifestyle. Considering the complexity of mechanisms involved in the regulation of aging process, up to this date there isn't a major, unifying theory which could explain them. As genetic/epigenetic and environmental factors both inevitably influence the aging process, here we present a review on the genetic and epigenetic regulation of the most important molecular and cellular mechanisms involved in the process of aging. Based on the studies on oxidative stress, metabolism, genome stability, epigenetic modifications and cellular senescence in animal models and humans, we give an overview of key genetic and molecular pathways related to aging. As most of genetic manipulations which influence the aging process also affect reproduction, we discuss aging in humans as a post-reproductive genetically determined process. After the age of reproductive success, aging continously progresses which clinically coincides with the onset of most chronic diseases, cancers and dementions. As evolution shapes the genomes for reproductive success and not for post-reproductive survival, aging could be defined as a protective mechanism which ensures the preservation and progress of species through the modification, trasmission and improvement of genetic material. PMID:19662799

  17. Databases for genetic services. Current usages and future directions.

    PubMed

    Meaney, F J

    1987-06-01

    Computer-based systems for the management of data in clinical genetics have become increasingly available for patient information storage and retrieval, evaluation and diagnosis, and pedigree data. The need for a national genetic services database has been recognized, and federal grants have provided funds for the development of state and regional databases for the evaluation of genetic services. Continuation of federal funding and the development of data systems that allow local, state, and regional needs to be met are essential for any progress to be made toward a national database. PMID:3668409

  18. Dengue Type 4 Live-Attenuated Vaccine Viruses Passaged in Vero Cells Affect Genetic Stability and Dengue-Induced Hemorrhaging in Mice

    PubMed Central

    Lee, Hsiang-Chi; Yen, Yu-Ting; Chen, Wen-Yu; Wu-Hsieh, Betty A.; Wu, Suh-Chin

    2011-01-01

    Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4) virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3′ NCR 30-nucleotide deletion mutant DEN-4 2AΔ30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2AΔ30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2AΔ30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2AΔ30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q438H, E-V463L, NS2B-Q78H, and NS2B-A113T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine development. PMID:22053180

  19. The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development.

    PubMed

    Chang, Ping-Chin; Chen, Shou-Chien; Chen, Kow-Tong

    2016-01-01

    Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing. PMID:27618078

  20. Current Understanding of the Genetic Architecture of Rhegmatogenous Retinal Detachment.

    PubMed

    Johnston, Timothy; Chandra, Aman; Hewitt, Alex W

    2016-06-01

    Rhegmatogenous retinal detachment (RRD) is a common and potentially blinding surgical retinal disease. While the precise molecular mechanisms leading to RRD are poorly understood, there is an increasing body of literature supporting the role of heritable factors in the pathogenesis of the condition. Much work has been undertaken investigating genes important in syndromic forms of RRD (e.g., Stickler, Wagner Syndrome, etc.) and research pertaining to genetic investigations of idiopathic or non-syndromic RRD has also recently been reported. To date, at least 12 genetic loci have been implicated in the development of syndromes of which RRD is a feature. A recent GWAS identified five loci implicated in the development of idiopathic RRD.This article provides an overview of the genetic mechanisms of both syndromic and idiopathic RRD. The genetics of predisposing conditions, such as myopia and lattice degeneration, are also discussed. PMID:26757352

  1. Currently Clinical Views on Genetics of Wilson's Disease

    PubMed Central

    Chen, Chen; Shen, Bo; Xiao, Jia-Jia; Wu, Rong; Canning, Sarah Jane Duff; Wang, Xiao-Ping

    2015-01-01

    Objective: The objective of this study was to review the research on clinical genetics of Wilson's disease (WD). Data Sources: We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic, ATP7B gene, gene mutation, genotype, phenotype. Study Selection: Publications about the ATP7B gene and protein function associated with clinical features were selected. Results: Wilson's disease, also named hepatolenticular degeneration, is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene ATP7B. Decreased biliary copper excretion and reduced incorporation of copper into apoceruloplasmin caused by defunctionalization of ATP7B protein lead to accumulation of copper in many tissues and organs, including liver, brain, and cornea, finally resulting in liver disease and extrapyramidal symptoms. It is the most common genetic neurological disorder in the onset of adolescents, second to muscular dystrophy in China. Early diagnosis and medical therapy are of great significance for improving the prognosis of WD patients. However, diagnosis of this disease is usually difficult because of its complicated phenotypes. In the last 10 years, an increasing number of clinical studies have used molecular genetics techniques. Improved diagnosis and prediction of the progression of this disease at the molecular level will aid in the development of more individualized and effective interventions, which is a key to transition from molecular genetic research to the clinical study. Conclusions: Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gene therapy for WD patients. PMID:26112727

  2. Giardia vaccination.

    PubMed

    Olson, M E; Ceri, H; Morck, D W

    2000-05-01

    Recently, a Giardia vaccine has become commercially available in the USA for prevention of clinical signs of giardiasis and reduction of cyst shedding in dogs and cats. The vaccine is based upon the current state of knowledge of Giardia antigenicity and immunology. Here, Merle Olson, Howard Ceri and Douglas Morck describe studies that led to the development of this vaccine and subsequent efficacy studies. Immunoprophylaxis and immunotherapeutic application of the vaccine are discussed. PMID:10782082

  3. Current Global Pricing For Human Papillomavirus Vaccines Brings The Greatest Economic Benefits To Rich Countries.

    PubMed

    Herlihy, Niamh; Hutubessy, Raymond; Jit, Mark

    2016-02-01

    Vaccinating females against human papillomavirus (HPV) prior to the debut of sexual activity is an effective way to prevent cervical cancer, yet vaccine uptake in low- and middle-income countries has been hindered by high vaccine prices. We created an economic model to estimate the distribution of the economic surplus-the sum of all health and economic benefits of a vaccine, minus the costs of development, production, and distribution-among different country income groups and manufacturers for a cohort of twelve-year-old females in 2012. We found that manufacturers may have received economic returns worth five times their original investment in HPV vaccine development. High-income countries gained the greatest economic surplus of any income category, realizing over five times more economic value per vaccinated female than low-income countries did. Subsidizing vaccine prices in low- and middle-income countries could both reduce financial barriers to vaccine adoption and still allow high-income countries to retain their economic surpluses and manufacturers to retain their profits. PMID:26858374

  4. CURRENT STATUS OF RECOMBINANT MAREK'S DISEASE VACCINES FOR CONTROL OF FUTURE OUTBREAKS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    More than 4 decades of vaccination has resulted in good control of Marek’s disease (MD). Although vaccination has dramatically reduced the incidence of the disease, more virulent viruses are emerging and the development of new control strategies is needed. Recently, the student of MD virus (MDV) g...

  5. Current Advances in Virus-Like Particles as a Vaccination Approach against HIV Infection

    PubMed Central

    Zhao, Chongbo; Ao, Zhujun; Yao, Xiaojian

    2016-01-01

    HIV-1 virus-like particles (VLPs) are promising vaccine candidates against HIV-1 infection. They are capable of preserving the native conformation of HIV-1 antigens and priming CD4+ and CD8+ T cell responses efficiently via cross presentation by both major histocompatibility complex (MHC) class I and II molecules. Progress has been achieved in the preclinical research of HIV-1 VLPs as prophylactic vaccines that induce broadly neutralizing antibodies and potent T cell responses. Moreover, the progress in HIV-1 dendritic cells (DC)-based immunotherapy provides us with a new vision for HIV-1 vaccine development. In this review, we describe updates from the past 5 years on the development of HIV-1 VLPs as a vaccine candidate and on the combined use of HIV particles with HIV-1 DC-based immunotherapy as efficient prophylactic and therapeutic vaccination strategies. PMID:26805898

  6. Effectiveness of vaccination with recombinant HpaA from Helicobacter pylori is influenced by host genetic background.

    PubMed

    Sutton, Philip; Doidge, Christopher; Pinczower, Gideon; Wilson, John; Harbour, Stacey; Swierczak, Agnieszka; Lee, Adrian

    2007-07-01

    Several studies have explored the production and immunogenicity of HpaA as a potential protective antigen against Helicobacter pylori but little is known regarding its protective capabilities. We therefore evaluated the protective efficacy of recombinant HpaA (rHpaA) as a candidate vaccine antigen against H. pylori. To explore the impact of genetic diversity, inbred and outbred mice were prophylactically and therapeutically immunized with rHpaA adjuvanted with cholera toxin (CT). Prophylactic immunization induced a reduction in bacterial colonization in BALB/c and QS mice, but was ineffective in C57BL/6 mice, despite induction of antigen-specific antibodies. By contrast, therapeutic immunization was effective in all three strains of mice. Prophylactic immunization with CT-adjuvanted rHpaA was more effective when delivered via the nasal route than following intragastric delivery in BALB/c mice. However, HpaA-mediated protection was inferior to that induced by bacterial lysate. Hence, protective efficacy is inducible with vaccines containing HpaA, most relevantly shown in an outbred population of mice. The effectiveness of protection induced by HpaA antigen was influenced by host genetics and was less effective than lysate. HpaA therefore has potential for the development of effective immunization against H. pylori but this would probably entail the antigen to be one component of a multiantigenic vaccine. PMID:17567282

  7. Development of a full-length cDNA-derived enterovirus A71 vaccine candidate using reverse genetics technology.

    PubMed

    Yang, Ya-Ting; Chow, Yen-Hung; Hsiao, Kuang-Nan; Hu, Kai-Chieh; Chiang, Jen-Ron; Wu, Suh-Chin; Chong, Pele; Liu, Chia-Chyi

    2016-08-01

    Enterovirus A71 (EV-A71) is responsible for epidemics of hand, foot and mouth disease (HFMD) in young children. To circumvent difficulties in obtaining clinical enterovirus isolates that might be contaminated with other viruses, a platform technology was developed to quickly generate vaccine virus strains based on the published enterovirus genomic sequences. A recombinant plasmid containing the full-length infectious cDNA clone of EV-A71 vaccine strain E59 was directly generated after transfecting the recombinant plasmid into Vero, RD or HEK293A cells, and phenotypic characteristics similar to the parental strain were observed. The cDNA-derived infectious EV-A71 virus grown in Vero cells produced relatively stable virus titers in both T-flasks and microcarrier culture systems. To evaluate the genetic stability of the cDNA-derived EV-A71 viruses, the immunodominant structural proteins, VP1 and VP2, of the recombinant EV-A71 viruses were sequenced and analyzed. The cDNA-derived EV-A71 virus showed weak pathogenicity in a human SCARB2 mouse model. These results show the successful generation of a recombinant virus derived from a published viral genomic sequence that demonstrated good genetic stability and viral yields, which could represent an efficient and safe vaccine strain for cGMP-grade manufacturing. PMID:27387826

  8. Genetic improvement of brewer's yeast: current state, perspectives and limits.

    PubMed

    Saerens, Sofie M G; Duong, C Thuy; Nevoigt, Elke

    2010-05-01

    Brewer's yeast strain optimisation may lead to a more efficient beer production process, better final quality or healthier beer. However, brewer's yeast genetic improvement is very challenging, especially true when it comes to lager brewer's yeast (Saccharomyces pastorianus) which contributes to 90% of the total beer market. This yeast is a genetic hybrid and allopolyploid. While early studies applying traditional genetic approaches encountered many problems, the development of rational metabolic engineering strategies successfully introduced many desired properties into brewer's yeast. Recently, the first genome sequence of a lager brewer's strain became available. This has opened the door for applying advanced omics technologies and facilitating inverse metabolic engineering strategies. The latter approach takes advantage of natural diversity and aims at identifying and transferring the crucial genetic information for an interesting phenotype. In this way, strains can be optimised by introducing "natural" mutations. However, even when it comes to self-cloned strains, severe concerns about genetically modified organisms used in the food and beverage industry are still a major hurdle for any commercialisation. Therefore, research efforts will aim at developing new sophisticated screening methods for the isolation of natural mutants with the desired properties which are based on the knowledge of genotype-phenotype linkage. PMID:20195857

  9. Current issues of personnel and laboratory practices in genetic testing

    PubMed Central

    Mark, Hon Fong Louie; Kelly, Thaddeus; Watson, Michael S; Hoeltge, Gerald; Miller, Wayne A; Beauregard, Laurent

    1995-01-01

    As genetic testing is an area with implications extending far beyond that of the primary patient, it is appropriately an area that is under increased scrutiny. To ensure that high quality is maintained in the delivery of genetic services, several agencies have developed standards and guidelines. The present article summarises important recommendations made by the American College of Medical Genetics (ACMG), the College of American Pathologists (CAP), the US Health Care Financing Administration (HCFA), and the US Food and Drug Administration (FDA) as they relate to genetic testing. Some of the standards are based on voluntary compliance, whereas others have the force of regulation. They all address issues of personnel credentials, laboratory operations, and the most critical quality assurance and control measures for diagnostic laboratories from the perspective of various agencies. In most instances, the standards promulgated by these agencies are offered as minimum criteria. The exact impact of these regulations on the practice of medical genetics has yet to be established. Images PMID:8558555

  10. Classical swine fever virus marker vaccine strain CP7_E2alf: genetic stability in vitro and in vivo.

    PubMed

    Goller, Katja V; Dräger, Carolin; Höper, Dirk; Beer, Martin; Blome, Sandra

    2015-12-01

    Recently, CP7_E2alf (SuvaxynCSF Marker), a live marker vaccine against classical swine fever virus, was licensed through the European Medicines Agency. For application of such a genetically engineered virus under field conditions, knowledge about its genetic stability is essential. Here, we report on stability studies that were conducted to assess and compare the mutation rate of CP7_E2alf in vitro and in vivo. Sequence analyses upon passaging confirmed the high stability of CP7_E2alf, and no recombination events were observed in the experimental setup. The data obtained in this study confirm the genetic stability of CP7_E2alf as an important safety component. PMID:26392285

  11. Efficacy of cellular vaccines and genetic adjuvants against bacterial kidney disease in chinook salmon (Oncorhynchus tshawytscha).

    PubMed

    Rhodes, Linda D; Rathbone, Cindra K; Corbett, Stephen C; Harrell, Lee W; Strom, Mark S

    2004-04-01

    DNA adjuvants and whole bacterial cell vaccines against bacterial kidney disease (BKD) were tested in juvenile chinook salmon. Whole cell vaccines of either a nonpathogenic Arthrobacter spp. or an attenuated Renibacterium salmoninarum strain provided limited prophylactic protection against acute intraperitoneal challenge with virulent R. salmoninarum, and the addition of either synthetic oligodeoxynucleotides or purified R. salmoninarum genomic DNA as adjuvants did not increase protection. However, a combination of both whole cell vaccines significantly increased survival among fish naturally infected with R. salmoninarum, and the surviving fish treated with the combination vaccine exhibited reduced levels of bacterial antigens in the kidney. This is the first demonstration of a potential therapeutic effect of a whole cell vaccine against BKD. PMID:15123289

  12. Detection by RT-PCR and genetic characterization of canine distemper virus from vaccinated and non-vaccinated dogs in Argentina.

    PubMed

    Calderon, Marina Gallo; Remorini, Patricia; Periolo, Osvaldo; Iglesias, Marcela; Mattion, Nora; La Torre, José

    2007-12-15

    RT-PCR was used to detect canine distemper virus (CDV) RNA in clotted blood from Argentine domestic dogs. The NP gene was detected in 73 out of 99 blood samples analyzed. The deduced amino acid sequence of these gene fragments showed 100% identity with the sequence of other wild-type and vaccine strains. A fragment of the hemagglutinin gene was amplified from 24 (32.9%) of the NP-RNA-positive clinical specimens. These H fragments were further analyzed by restriction fragment length polymorphism (RFLP) and sequencing. A single NdeI site was detected in all 24 wild-type strains but was absent in the vaccine strains. Phylogenetic analysis of the partial hemagglutinin amino acid sequences showed close clustering for local strains, clearly distinct from vaccine strains and other wild-type foreign CDV strains. One of the local strains, Arg 23, branched out of the root of the Argentine clade, close to the European strains, suggesting that two different pathogenic CDV genotypes are currently circulating in Argentina, one of them clearly predominant. PMID:17628358

  13. [Genetic Characteristics of Type 2 Vaccine-derived Poliovirus in Shanxi Province (China) in 2014].

    PubMed

    Yan, Dongrei; Li, Xiaolei; Zhang, Yong; Yang, Jianfang; Zhu, Shuangli; Wang, Dongyan; Zhang, Chuangye; Zhu, Hui; Xu, Wenbo

    2015-03-01

    The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China. PMID:26164941

  14. Genetic Analyses in Health Laboratories: Current Status and Expectations

    NASA Astrophysics Data System (ADS)

    Finotti, Alessia; Breveglieri, Giulia; Borgatti, Monica; Gambari, Roberto

    Genetic analyses performed in health laboratories involve adult patients, newborns, embryos/fetuses, pre-implanted pre-embryos, pre-fertilized oocytes and should meet the major medical needs of hospitals and pharmaceutical companies. Recent data support the concept that, in addition to diagnosis and prognosis, genetic analyses might lead to development of personalized therapy. Novel frontiers in genetic testing involve the development of single cell analyses and non-invasive assays, including those able to predict outcome of cancer pathologies by looking at circulating tumor cells, DNA, mRNA and microRNAs. In this respect, PCR-free diagnostics appears to be one of the most interesting and appealing approaches.

  15. Approaches for genetic purity testing of live recombinant viral vaccines using a human adenovirus:rabies model.

    PubMed Central

    Lutze-Wallace, C; Sapp, T; Nadin-Davis, S A; Wandeler, A

    1992-01-01

    A two part purity testing regimen for genetically engineered live viral vaccines is described using a human adenovirus 5: rabies glycoprotein gene recombinant as a model vaccine. Initially, restriction endonuclease analysis of the recombinant viral genome verified the integrity of the recombinant construct and identified the vector genome. The second stage employed the polymerase chain reaction to facilitate a more detailed study of the target rabies glycoprotein cassette. The size of the target region was predicted from known nucleic acid sequence information and compared to that obtained after electrophoresis with molecular weight standards. Digestion of the polymerase chain reaction product with a second restriction endonuclease cleaved the target into a number of small fragments. Resolution of the fragments by gel electrophoresis allowed analysis of the target region alone, verifying its identity and integrity. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:1477804

  16. A Killed, Genetically Engineered Derivative of a Wild-Type Extraintestinal Pathogenic E. coli strain is a Vaccine Candidate

    PubMed Central

    Russo, Thomas A.; Beanan, Janet M.; Olson, Ruth; Genagon, Stacy A.; MacDonald, Ulrike; Cope, John J.; Davidson, Bruce A.; Johnston, Brian; Johnson, James R.

    2007-01-01

    Infections due to extraintestinal pathogenic E. coli (ExPEC) result in significant morbidity, mortality and increased healthcare costs. An efficacious vaccine against ExPEC would be desirable. In this report we explore the use of killed-whole E. coli as a vaccine immunogen. Given the diversity of capsule and O-antigens in ExPEC we have hypothesized that alternative targets are viable vaccine candidates. We have also hypothesized that immunization with a genetically engineered strain that is deficient in the capsule and O-antigen will generate a greater immune response against antigens other than the capsular and O-antigen epitopes than a wild-type strain. Lastly, we hypothesize that mucosal immunization with killed E. coli has the potential to generate a significant immune response. In this study we demonstrated that nasal immunization with a formalin-killed ExPEC derivative deficient in capsule and O-antigen results in a significantly greater overall humoral response compared to its wild-type derivative (which demonstrates that capsule and/or the O-antigen impede the development of an optimal humoral immune response) and a significantly greater immune response against non-capsular and O-antigen epitopes. These antibodies also bound to a subset of heterologous ExPEC strains and enhanced neutrophil-mediated bactericidal activity against the homologous and a heterologous strain. Taken together these studies support the concept that formalin-killed genetically engineered ExPEC derivatives are whole cell vaccine candidates to prevent infections due to ExPEC. PMID:17306426

  17. Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine

    PubMed Central

    Griggs, A.; Lievens, M.; Abdulla, S.; Adjei, S.; Agbenyega, T.; Agnandji, S.T.; Aide, P.; Anderson, S.; Ansong, D.; Aponte, J.J.; Asante, K.P.; Bejon, P.; Birkett, A.J.; Bruls, M.; Connolly, K.M.; D’Alessandro, U.; Dobaño, C.; Gesase, S.; Greenwood, B.; Grimsby, J.; Tinto, H.; Hamel, M.J.; Hoffman, I.; Kamthunzi, P.; Kariuki, S.; Kremsner, P.G.; Leach, A.; Lell, B.; Lennon, N.J.; Lusingu, J.; Marsh, K.; Martinson, F.; Molel, J.T.; Moss, E.L.; Njuguna, P.; Ockenhouse, C.F.; Ogutu, B. Ragama; Otieno, W.; Otieno, L.; Otieno, K.; Owusu-Agyei, S.; Park, D.J.; Pellé, K.; Robbins, D.; Russ, C.; Ryan, E.M.; Sacarlal, J.; Sogoloff, B.; Sorgho, H.; Tanner, M.; Theander, T.; Valea, I.; Volkman, S.K.; Yu, Q.; Lapierre, D.; Birren, B.W.; Gilbert, P.B.; Wirth, D.F.

    2016-01-01

    BACKGROUND The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS We used polymerase chain reaction–based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P = 0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P = 0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health

  18. Safety and Efficacy of a Genetic Vaccine Targeting Telomerase Plus Chemotherapy for the Therapy of Canine B-Cell Lymphoma

    PubMed Central

    Gavazza, Alessandra; Lubas, George; Fridman, Arthur; Peruzzi, Daniela; Impellizeri, Joseph A.; Luberto, Laura; Marra, Emanuele; Roscilli, Giuseppe; Ciliberto, Gennaro

    2013-01-01

    Abstract Client-owned pet dogs represent exceptional translational models for advancement of cancer research because they reflect the complex heterogeneity observed in human cancer. We have recently shown that a genetic vaccine targeting dog telomerase reverse transcriptase (dTERT) and based on adenovirus DNA electro-gene-transfer (Ad/DNA-EGT) technology can induce strong cell-mediated immune responses against this tumor antigen and increase overall survival of dogs affected by B-cell lymphosarcoma (LSA) in comparison with historical controls when combined with a cyclophosphamide, vincristine, and prednisone (COP) chemotherapy regimen. Here, we have conducted a double-arm clinical trial with an extended number of LSA patients, measured the antigen-specific immune response, and evaluated potential toxic effects of the immunotherapy along with a follow-up of patients survival for 3.5 years. The immune response was measured by enzyme-linked immunospot assay. The expression of dTERT was quantified by quantitative polymerase chain reaction. Changes in hematological parameters, local/systemic toxicity or organic dysfunction and fever were monitored over time during the treatment. dTERT-specific cell-mediated immune responses were induced in almost all treated animals. No adverse effects were observed in any dog patient that underwent treatment. The overall survival time of vaccine/COP-treated dogs was significantly increased over the COP-only cohort (>76.1 vs. 29.3 weeks, respectively, p<0.0001). There was a significant association between dTERT expression levels in LSA cells and overall survival among vaccinated patients. In conclusion, Ad/DNA-EGT-based cancer vaccine against dTERT in combination with COP chemotherapy is safe and significantly prolongs the survival of LSA canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and support the evaluation of this approach for other cancer types as well as the translation of this approach to human

  19. Rift Valley fever MP-12 vaccine Phase 2 clinical trial: Safety, immunogenicity, and genetic characterization of virus isolates.

    PubMed

    Pittman, Phillip R; Norris, Sarah L; Brown, Elizabeth S; Ranadive, Manmohan V; Schibly, Barbara A; Bettinger, George E; Lokugamage, Nandadeva; Korman, Lawrence; Morrill, John C; Peters, Clarence J

    2016-01-20

    An outbreak or deliberate release of Rift Valley fever (RVF) virus could have serious public health and socioeconomic consequences. A safe RVF vaccine capable of eliciting long-lasting immunity after a single injection is urgently needed. The live attenuated RVF MP-12 vaccine candidate has shown promise in Phase 1 clinical trials; no evidence of reversion to virulence has been identified in numerous animal studies. The objective of this Phase 2 clinical trial was to (a) further examine the safety and immunogenicity of RVF MP-12 in RVF virus-naïve humans and (b) characterize isolates of RVF MP-12 virus recovered from the blood of vaccinated subjects to evaluate the genetic stability of MP-12 attenuation. We found that RVF MP-12 was well tolerated, causing mostly mild reactions that resolved without sequelae. Of 19 subjects, 18 (95%) and 19 (100%) achieved, respectively, 80% and 50% plaque reduction neutralization titers (PRNT80 and PRNT50)≥1:20 by postvaccination day 28. All 18 PRNT80 responders maintained PRNT80 and PRNT50≥1:40 until at least postvaccination month 12. Viremia was undetectable in the plasma of any subject by direct plaque assay techniques. However, 5 of 19 vaccinees were positive for MP-12 isolates in plasma by blind passage of plasma on Vero cells. Vaccine virus was also recovered from buffy coat material from one of those vaccinees and from one additional vaccinee. Through RNA sequencing of MP-12 isolates, we found no reversions of amino acids to those of the parent virulent virus (strain ZH548). Five years after a single dose of RVF MP-12 vaccine, 8 of 9 vaccinees (89%) maintained a PRNT80≥1:20. These findings support the continued development of RVF MP-12 as a countermeasure against RVF virus in humans. PMID:26706271

  20. Rational Antibody-based HIV-1 Vaccine Design: Current Approaches and Future Directions

    PubMed Central

    Walker, Laura M.; Burton, Dennis R.

    2010-01-01

    Many anti-viral vaccines elicit neutralizing antibodies as a correlate of protection. For HIV, given the huge variability of the virus, it is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be crucial in a successful vaccine against the virus. Unfortunately, despite many efforts, the development of an immunogen that elicits bNAbs remains elusive. However, recent structural studies of HIV-1 Env proteins, generation of novel bNAbs, maturation of technologies for the isolation of further antibodies, insights into the requirements for antibody-mediated protection, and novel vaccination approaches are providing grounds for renewed optimism. PMID:20299194

  1. Current Genetic Discoveries and Education: "Strengths, Opportunities, and Limitations"

    ERIC Educational Resources Information Center

    Bates, Timothy C.

    2008-01-01

    This article notes that many key positive developments in education originated in research on the structure and genetics of abilities, providing primary evidence for ability in disadvantaged groups and playing a critical role in demonstrating the existence of developmental learning disorders and effective interventions. It is argued that new work…

  2. Current Progress of Genetically Engineered Pig Models for Biomedical Research

    PubMed Central

    Gün, Gökhan

    2014-01-01

    Abstract The first transgenic pigs were generated for agricultural purposes about three decades ago. Since then, the micromanipulation techniques of pig oocytes and embryos expanded from pronuclear injection of foreign DNA to somatic cell nuclear transfer, intracytoplasmic sperm injection-mediated gene transfer, lentiviral transduction, and cytoplasmic injection. Mechanistically, the passive transgenesis approach based on random integration of foreign DNA was developed to active genetic engineering techniques based on the transient activity of ectopic enzymes, such as transposases, recombinases, and programmable nucleases. Whole-genome sequencing and annotation of advanced genome maps of the pig complemented these developments. The full implementation of these tools promises to immensely increase the efficiency and, in parallel, to reduce the costs for the generation of genetically engineered pigs. Today, the major application of genetically engineered pigs is found in the field of biomedical disease modeling. It is anticipated that genetically engineered pigs will increasingly be used in biomedical research, since this model shows several similarities to humans with regard to physiology, metabolism, genome organization, pathology, and aging. PMID:25469311

  3. Psychological Issues in Cancer Genetics: Current Research and Future Priorities.

    ERIC Educational Resources Information Center

    Hopwood, Penelope

    1997-01-01

    Data concerning the psychological impact of high risk of cancer are reviewed, including implications of genetic testing, breast screening,and accuracy of women's risk estimates. Work in progress on prophylactic mastectomy and chemoprevention is reviewed. Research on cancer families, and interventions and prevention strategies for high-risk…

  4. Genetics in diabetic retinopathy: current concepts and new insights.

    PubMed

    Simó-Servat, Olga; Hernández, Cristina; Simó, Rafael

    2013-08-01

    There is emerging evidence which indicates the essential role of genetic factors in the development of diabetic retinopathy (DR). In this regard it should be highlighted that genetic factors account for 25-50% of the risk of developing DR. Therefore, the use of genetic analysis to identify those diabetic patients most prone to developing DR might be useful in designing a more individualized treatment. In this regard, there are three main research strategies: candidate gene studies, linkage studies and Genome-Wide Association Studies (GWAS). In the candidate gene approach, several genes encoding proteins closely related to DR development have been analyzed. The linkage studies analyze shared alleles among family members with DR under the assumption that these predispose to a more aggressive development of DR. Finally, Genome-Wide Association Studies (GWAS) are a new tool involving a massive evaluation of single nucleotide polymorphisms (SNP) in large samples. In this review the available information using these three methodologies is critically analyzed. A genetic approach in order to identify new candidates in the pathogenesis of DR would permit us to design more targeted therapeutic strategies in order to decrease this devastating complication of diabetes. Basic researchers, ophthalmologists, diabetologists and geneticists should work together in order to gain new insights into this issue. PMID:24403848

  5. Current genetic technologies to improve efficiency of livestock production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Modern molecular technologies are making revolutionary advances in genetics and genomics of human and animal species. The resources available in livestock species have been making parallel advances to that of human and rodents and are allowing for the discovery of gene function for complex traits. G...

  6. Construction of a Live-Attenuated HIV-1 Vaccine through Genetic Code Expansion

    PubMed Central

    Wang, Nanxi; Li, Yue; Niu, Wei; Sun, Ming; Cerny, Ronald; Li, Qingsheng; Guo, Jiantao

    2016-01-01

    A safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed to combat the worldwide AIDS pandemic, but still remains elusive. The fact that uncontrolled replication of an attenuated vaccine can lead to regaining of its virulence creates safety concerns precluding many vaccines from clinical application. We introduce a novel approach to control HIV-1 replication, which entails the manipulation of essential HIV-1 protein biosynthesis through unnatural amino acid (UAA*)-mediated suppression of genome-encoded blank codon. We successfully demonstrate that HIV-1 replication can be precisely turned on and off in vitro. PMID:24715496

  7. Models of the impact of dengue vaccines: a review of current research and potential approaches.

    PubMed

    Johansson, Michael A; Hombach, Joachim; Cummings, Derek A T

    2011-08-11

    Vaccination reduces transmission of pathogens directly, by preventing individual infections, and indirectly, by reducing the probability of contact between infected individuals and susceptible ones. The potential combined impact of future dengue vaccines can be estimated using mathematical models of transmission. However, there is considerable uncertainty in the structure of models that accurately represent dengue transmission dynamics. Here, we review models that could be used to assess the impact of future dengue immunization programmes. We also review approaches that have been used to validate and parameterize models. A key parameter of all approaches is the basic reproduction number, R(0), which can be used to determine the critical vaccination fraction to eliminate transmission. We review several methods that have been used to estimate this quantity. Finally, we discuss the characteristics of dengue vaccines that must be estimated to accurately assess their potential impact on dengue virus transmission. PMID:21699949

  8. Current progress in the development of a prophylactic vaccine for HIV-1

    PubMed Central

    Gamble, Lena J; Matthews, Qiana L

    2011-01-01

    Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts’ immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts. PMID:21267356

  9. Childhood Vaccine Schedule

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  10. Vaccines Stop Illness

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  11. Integrated Analysis of Genetic and Proteomic Data Identifies Biomarkers Associated with Adverse Events Following Smallpox Vaccination

    EPA Science Inventory

    Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experi...

  12. Genetics of Autism Spectrum Disorder: Current Status and Possible Clinical Applications

    PubMed Central

    2015-01-01

    Autism spectrum disorder (ASD) is one of the most complex behavioral disorders with a strong genetic influence. The objectives of this article are to review the current status of genetic research in ASD, and to provide information regarding the potential candidate genes, mutations, and genetic loci possibly related to pathogenesis in ASD. Investigations on monogenic causes of ASD, candidate genes among common variants, rare de novo mutations, and copy number variations are reviewed. The current possible clinical applications of the genetic knowledge and their future possibilities are highlighted. PMID:26713075

  13. Fish Vaccines in Aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination is a proven, cost-effective method to prevent infectious diseases in animals. Current fish vaccines can be categorized as killed fish vaccines or modified live vaccines. The major advantage of live vaccine is their ability to stimulate both cell-mediated and humoral immune responses for ...

  14. Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16).

    PubMed

    Dorneles, Elaine Maria Seles; de Faria, Ana Paula Paiva; Pauletti, Rebeca Barbosa; Santana, Jordana Almeida; Caldeira, George Afonso Vítor; Heinemann, Marcos Bryan; Titze-de-Almeida, Ricardo; Lage, Andrey Pereira

    2013-10-01

    The aims of the present study were (i) to assess the in vitro genetic stability of S19 and RB51 Brucella abortus vaccines strains and (ii) to evaluate the ability of multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) as a tool to be used in the quality control of live vaccines against brucellosis. Sixty-three batches of commercial S19 (n=53) and RB51 (n=10) vaccines, produced between 2006 and 2009, were used in this study. S19 and RB51 vaccines were obtained from, respectively, seven and two different manufacturers. Ten in vitro serial passages were performed on reference strains and on selected batches of commercial vaccines. All batches, reference strains and strains of serial passages were typed by the MLVA16. The results demonstrated that B. abortus S19 and RB51 vaccine strains are genetically stable and very homogeneous in their respective groups. Anyway, batches of S19 from one manufacturer and batches of RB51 from another presented genotypes distincts from the reference vaccine strains. In both cases, differences were found on locus Bruce07, which had addition of one repeat unit in the case of S19 batches and the deletion of one repeat unit in the case of RB51 batches. In summary, MLVA16 proved to be a molecular tool capable of discriminating small genomic variations and should be included in in vitro official tests. PMID:23933375

  15. Summary of clinical findings on Engerix-B, a genetically engineered yeast derived hepatitis B vaccine.

    PubMed

    André, F E; Safary, A

    1987-01-01

    Between February 1984 and August 1986 results have been obtained in 58 completed or ongoing clinical studies by 33 investigators in 19 countries on a yeast-derived recombinant DNA hepatitis B vaccine (Engerix-B). Among the 6100 subjects enrolled in these studies, 5664 subjects (150 normal neonates, 178 neonates of hepatitis B carrier mothers, 330 children aged 3-10 years, 3697 young healthy adults, 438 homosexual males, 110 older healthy adults, 139 drug addicts, 262 institutionalized mentally retarded patients, 59 thalassaemics, 25 sicklaemics, 270 patients on chronic haemodialysis and 6 haemophiliacs) received one or more (up to 4) injections of different doses of the yeast-derived vaccine according to either a 0, 1, 2, and 12 month or a 0, 1, and 6 month vaccination schedule. In randomized comparative studies 436 subjects received either one of two commercially available plasma-derived vaccines. The results reviewed in the present summary have shown that Engerix-B is safe, clinically well tolerated, gives an anti-HBs response which is qualitatively and quantitatively similar to that obtained with plasma-derived vaccines and confers protection against infection and disease. Engerix-B can be considered as a valid alternative to existing hepatitis B vaccines. PMID:3317357

  16. Clinical experience with respiratory syncytial virus vaccines.

    PubMed

    Piedra, Pedro A

    2003-02-01

    Respiratory syncytial virus (RSV) infection is at times associated with life-threatening lower respiratory tract illness in infancy. Severe infection during the first year of life may be an important risk factor or indicator for the development of asthma in early childhood. Severe infections primarily occur in healthy infants, and young infants and children with specific risk factors. However, RSV causes respiratory infections in all age groups. Indeed it is now recognized that RSV disease is responsible for significant morbidity and mortality in the geriatric population. RSV infection remains difficult to treat, and prevention is a worldwide goal. For this reason there has been an intensive effort to develop an effective and safe RSV vaccine. Initial infection with RSV affords limited protection to reinfection, yet repeated episodes decrease the risk for lower respiratory tract illness. In the 20 years from 1960 to 1980, trials of several candidate RSV vaccines failed to attain the desired safety and protection against natural infection. Some vaccine types either failed to elicit immunogenicity, as with the live subcutaneous vaccine, or resulted in exaggerated disease on natural exposure to the virus, as with the formalin-inactivated (FI) type. Currently vaccine candidates are being developed based on the molecular virology of RSV. Recent formulations of candidate RSV vaccines have focused on subunit vaccines [such as purified fusion protein (PFP)], subunit vaccines combined with nonspecific immune activating adjuvants, live attenuated vaccines (including cold passaged, temperature-sensitive or cpts mutants), genetically engineered live attenuated vaccines and polypeptide vaccines. PMID:12671459

  17. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

    PubMed Central

    Di Ciaula, Agostino; Wang, David Q.-H.; Bonfrate, Leonilde; Portincasa, Piero

    2013-01-01

    Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia) are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs) may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk. PMID:23691293

  18. The genetics of premature ovarian failure: current perspectives

    PubMed Central

    Chapman, Chevy; Cree, Lynsey; Shelling, Andrew N

    2015-01-01

    Premature ovarian failure (POF) is a common cause of infertility in women, characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40. Many genes have been identified over the past few years that contribute to the development of POF. However, few genes have been identified that can explain a substantial proportion of cases of POF. The unbiased approaches of genome-wide association studies and next-generation sequencing technologies have identified several novel genes implicated in POF. As only a small proportion of genes influencing idiopathic POF have been identified thus far, it remains to be determined how many genes and molecular pathways may influence idiopathic POF development. However, owing to POF’s diverse etiology and genetic heterogeneity, we expect to see the contribution of several new and novel molecular pathways that will greatly enhance our understanding of the regulation of ovarian function. Future genetic studies in large cohorts of well-defined, unrelated, idiopathic POF patients will provide a great opportunity to identify the missing heritability of idiopathic POF. The identification of several causative genes may allow for early detection and would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help direct potential targets for future treatment. PMID:26445561

  19. Do current cost-effectiveness analyses reflect the full value of childhood vaccination in Europe?

    PubMed Central

    Brüggenjürgen, Bernd; Lorrot, Mathie; Sheppard, Fiona R; Rémy, Vanessa

    2014-01-01

    Economic evaluation of vaccination programs can be challenging and does not always fully capture the benefits provided. Reasons for this include the difficulties incurred in accurately capturing the health and economic impact of infectious diseases and how different diseases may interact with each other. Rotavirus infection, for example, peaks at a similar time than other infectious diseases, such as RSV and influenza, which can cause hospital overcrowding and disruption, and may pose a risk to more vulnerable children due to limited availability of isolation facilities. Another challenge, specific to evaluating childhood vaccination, is that QoL cannot be accurately measured in children due to a lack of validated instruments. Childhood diseases also incur a care giver burden, due to the need for parents to take time off work, and this is important to consider. Finally, for diseases such as RVGE, cost-effectiveness analyses in which longer time horizons are considered may not reflect the short-term benefits of vaccination. Further quantification of the economic impact of childhood diseases is thus required to fully highlight the true benefits of childhood vaccination that may be realized. Herein we explore the limitations of existing economic evaluations for childhood vaccination, and how economic analyses could be better adapted in future. PMID:25424934

  20. Thiomersal-containing vaccines - a review of the current state of knowledge.

    PubMed

    Gołoś, Aleksandra; Lutyńska, Anna

    2015-01-01

    Thiomersal is an organomercury compound known for its antiseptic and antifungal properties and used as an antibacterial agent in pharmaceutical products, including vaccines and other injectable biological products. In recent years, concerns about the possible link between immunization with thiomersal-containing vaccines and autism development have grown. Many case-control and cohort studies have been conducted on a number of populations, and none of them have confirmed the hypothetical relation between thiomersal and increased risk of autism spectrum disorders (ASDs) development. It is also confirmed by the fact, that since 1999, number of thiomersal-containing vaccines used worldwide is decreasing year by year, while the prevalence of ASDs cases is rising. There are no contraindications to the use of vaccines with thiomersal in infants, children and non-pregnant women. The risk of serious complications associated with the development of diseases in unvaccinated individuals far outweighs the potential risk of adverse consequences associated with immunization with thiomersal-containing vaccines. PMID:25862449

  1. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.

    PubMed

    Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

    2014-01-01

    Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

  2. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

    PubMed Central

    Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

    2014-01-01

    Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

  3. Developing mRNA-vaccine technologies

    PubMed Central

    Schlake, Thomas; Thess, Andreas; Fotin-Mleczek, Mariola; Kallen, Karl-Josef

    2012-01-01

    mRNA vaccines combine desirable immunological properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction. In addition, mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome. Because any protein can be expressed from mRNA without the need to adjust the production process, mRNA vaccines also offer maximum flexibility with respect to development. Taken together, mRNA presents a promising vector that may well become the basis of a game-changing vaccine technology platform. Here, we outline the current knowledge regarding different aspects that should be considered when developing an mRNA-based vaccine technology. PMID:23064118

  4. Genetic Vulnerability as a Distal Risk Factor for Suicidal Behaviour: Historical Perspective and Current Knowledge

    PubMed Central

    ANDRIESSEN, Karl; VIDETIC-PASKA, Alja

    2015-01-01

    Introduction Suicide is a multidimensional problem. Observations of family history of suicide suggest the existence of a genetic vulnerability to suicidal behaviour. Aim Starting with a historical perspective, the article reviews current knowledge of a genetic vulnerability to suicidal behaviour, distinct from the genetic vulnerability to psychiatric disorders, focused on clinical and population-based studies, and findings from recent molecular genetics association studies. Method The review includes peer-reviewed research articles and review papers from the professional literature in English language, retrieved from PubMed/Medline and PsycINFO. Results The research literature confirms a existence of a genetic vulnerability to suicidal behaviour. Even though the results of individual studies are difficult to compare, genetic influences could explain up to half of the variance of the occurrence of suicide. Conclusion Genetic vulnerability could be a distal risk factor for suicide, which helps us to understand the occurrence of suicide among vulnerable people. Ethical implications of such vulnerability are highlighted.

  5. Rising rates of vaccine exemptions: problems with current policy and more promising remedies.

    PubMed

    Constable, Catherine; Blank, Nina R; Caplan, Arthur L

    2014-04-01

    Parents of school-age children are increasingly claiming nonmedical exemptions to refuse vaccinations required for school entry. The resultant unvaccinated pockets in many areas of the country have been linked with outbreaks of vaccine-preventable diseases. Many states are now focused on reducing rates of nonmedical exemptions by making exemption processes more restrictive or burdensome for the exemptor. These strategies, however, pose ethical problems and may ultimately be inadequate. A shift to strategies that raise the financial liabilities of exemptors may lead to better success and prove ethically more sound. Potential areas of reform include tax law, health insurance, and private school funding programs. We advocate an approach that combines this type of incentive with more effective vaccination education. PMID:24530934

  6. Therapeutic vaccines and immunotherapy in castration-resistant prostate cancer: current progress and clinical applications.

    PubMed

    Gulley, James L; Madan, Ravi A; Heery, Christopher R

    2013-01-01

    Results of recent clinical trials have intensified interest in immunotherapy for cancer. Among the most promising candidates for immunotherapy are patients with prostate cancer. Results of therapeutic vaccine clinical trials in this population have suggested statistically significant and clinically meaningful improvements in overall survival, with substantially fewer side effects than with chemotherapy. Of particular interest are sipuleucel-T, the first U.S. Food and Drug Administration-approved therapeutic cancer vaccine, and PSA-TRICOM (PROSTVAC), a therapeutic cancer vaccine in phase III testing. The immune checkpoint inhibitor ipilimumab is also stirring considerable interest, with two phase III trials ongoing in prostate cancer. This article highlights data emerging from these trials and addresses remaining questions and practical clinical implications of this therapeutic strategy. PMID:23714490

  7. [Current issues of epidemiology and vaccine prophylaxis of "children" airborne infections in the armies (Navy)].

    PubMed

    Belov, A B; Ogarkov, P I

    2011-04-01

    It highlights the problems associated with the epidemiological situation of the morbidity of the population and the military personnel with infections, which recently were "infant"--measles, mumps, rubella, diphtheria and other infections, controlled now by means of immunization. There is no alternative to the mass immunization of children and adolescents to achieve highly efficient vaccine-resistant sporadic incidence of these infections. However, amid the successes achieved, regular "grow-up" disease causes these infections spread vaccination for adults who are at risk. In military units there are similar conditions, they increase the risk of both infection and disease, especially among conscripts. The ways to improve vaccination calendars troops are discussed, including held for epidemical indications, the need for immunization of groups at risk of chicken pox, and in the future--and against other "childhood" diseases. PMID:21770322

  8. Proteomic evaluation of genetically modified crops: current status and challenges.

    PubMed

    Gong, Chun Yan; Wang, Tai

    2013-01-01

    Hectares of genetically modified (GM) crops have increased exponentially since 1996, when such crops began to be commercialized. GM biotechnology, together with conventional breeding, has become the main approach to improving agronomic traits of crops. However, people are concerned about the safety of GM crops, especially GM-derived food and feed. Many efforts have been made to evaluate the unintended effects caused by the introduction of exogenous genes. "Omics" techniques have advantages over targeted analysis in evaluating such crops because of their use of high-throughput screening. Proteins are key players in gene function and are directly involved in metabolism and cellular development or have roles as toxins, antinutrients, or allergens, which are essential for human health. Thus, proteomics can be expected to become one of the most useful tools in safety assessment. This review assesses the potential of proteomics in evaluating various GM crops. We further describe the challenges in ensuring homogeneity and sensitivity in detection techniques. PMID:23471542

  9. Reduced dose human papillomavirus vaccination: an update of the current state-of-the-art.

    PubMed

    Toh, Zheng Quan; Licciardi, Paul V; Fong, James; Garland, Suzanne M; Tabrizi, Sepehr N; Russell, Fiona M; Mulholland, Edward K

    2015-09-22

    Human papillomavirus (HPV) infection is the primary cause of genital warts, some oropharyngeal cancers and anogenital cancers, including cervical, vagina, vulvar, anal and penile cancers. Primary prevention of cervical cancer requires the prevention of high-risk HPV infections, particularly HPV genotypes 16 and 18. Both Gardasil® and Cervarix® vaccines when administered by a three-dose schedule have been demonstrated to be effective against cervical, vulva, and vaginal cancer precursors from vaccine genotypes in phase III clinical trials, and post-marketing studies; Gardasil® vaccine also offers additional protection against anal cancer precursors. However, high costs of HPV vaccines and the logistics of delivering a three-dose schedule over 6 months are challenging in countries with limited resources. Several studies have demonstrated non-inferiority in antibody response between adolescents (9-15 years old) who received two doses (6 months apart) and women (>15 years old) who received the standard three-dose schedule. These studies provided evidence for the World Health Organization and European Medical Association to revise its recommendation to give two instead of three doses of HPV vaccine to adolescents below 15 years of age, provided the 2nd dose is given 6 months apart. Although reduced dose schedules can alleviate costs and logistics associated with HPV vaccination, especially in resource-poor countries, there are still gaps in this area of research, particularly regarding long-term protection. This review discusses the findings on antibody response and clinical outcomes in studies evaluating reduced dose HPV schedules, and highlights the important considerations of its implementation. In addition, other important immunological biomarkers that may be associated with long-term protection are highlighted and discussed. PMID:26271829

  10. Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

    PubMed

    Wagner, James M; Alper, Hal S

    2016-04-01

    Coupling the tools of synthetic biology with traditional molecular genetic techniques can enable the rapid prototyping and optimization of yeast strains. While the era of yeast synthetic biology began in the well-characterized model organism Saccharomyces cerevisiae, it is swiftly expanding to include non-conventional yeast production systems such as Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. These yeasts already have roles in the manufacture of vaccines, therapeutic proteins, food additives, and biorenewable chemicals, but recent synthetic biology advances have the potential to greatly expand and diversify their impact on biotechnology. In this review, we summarize the development of synthetic biological tools (including promoters and terminators) and enabling molecular genetics approaches that have been applied in these four promising alternative biomanufacturing platforms. An emphasis is placed on synthetic parts and genome editing tools. Finally, we discuss examples of synthetic tools developed in other organisms that can be adapted or optimized for these hosts in the near future. PMID:26701310

  11. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  12. Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: current status and future direction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Within a few years of its emergence in the late 1980's, the PRRS virus had spread globally to become the foremost infectious disease concern for the pork industry. Since 1994, modified live-attenuated vaccines against porcine reproductive and respiratory syndrome virus (PRRSV-MLV) have been widely u...

  13. Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

    PubMed

    Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

    2016-06-01

    Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID:26835746

  14. Genetics and bioethics: the current state of affairs.

    PubMed

    Williams, Erin D

    2002-01-01

    The pursuit of genetic knowledge has such emotional, social, scientific, and financial importance that it has been compared to the divine quest for the Holy Grail, and to the calamity of opening Pandora's Box. Therefore, it comes as no surprise that the recent announcement of a completed blueprint for the human genome has fueled calls for both increased research and increased precautions. This new era, which holds the potential promise of advances in medicine, agriculture and other areas, also requires the careful investigation of a myriad of issues. Those issues such as informed consent, patenting, privacy, and confidentiality, have been explored in at least some detail. Others, such as equity, mutual respect, empowering education, consensus building, and planning for long-term survival, have not been as fully examined, nor have they been as comprehensively integrated into mainstream thinking. To facilitate this, we need to implement an ethical approach that leads us to ask critical questions about the appropriate use of our new tools. PMID:15739301

  15. Proteomic evaluation of genetically modified crops: current status and challenges

    PubMed Central

    Gong, Chun Yan; Wang, Tai

    2013-01-01

    Hectares of genetically modified (GM) crops have increased exponentially since 1996, when such crops began to be commercialized. GM biotechnology, together with conventional breeding, has become the main approach to improving agronomic traits of crops. However, people are concerned about the safety of GM crops, especially GM-derived food and feed. Many efforts have been made to evaluate the unintended effects caused by the introduction of exogenous genes. “Omics” techniques have advantages over targeted analysis in evaluating such crops because of their use of high-throughput screening. Proteins are key players in gene function and are directly involved in metabolism and cellular development or have roles as toxins, antinutrients, or allergens, which are essential for human health. Thus, proteomics can be expected to become one of the most useful tools in safety assessment. This review assesses the potential of proteomics in evaluating various GM crops. We further describe the challenges in ensuring homogeneity and sensitivity in detection techniques. PMID:23471542

  16. HIV/AIDS and Vaccines

    MedlinePlus

    ... Prevention Research : Vaccines Subscribe Translate Text Size Print Vaccines What Are Vaccines and What Do They Do? A vaccine—also ... immune response against the disease. Is There a Vaccine for HIV? No. There is currently no vaccine ...

  17. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  18. Hepatitis Vaccines.

    PubMed

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  19. Traditional and New Influenza Vaccines

    PubMed Central

    Wong, Sook-San

    2013-01-01

    SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets. PMID:23824369

  20. GITRL as a genetic adjuvant enhances enterovirus 71 VP1 DNA vaccine immunogenicity.

    PubMed

    Yuan, Jing; Tang, Xinyi; Yin, Kai; Tian, Jie; Rui, Ke; Ma, Jie; Mao, Chaoming; Chen, Jianguo; Lu, Liwei; Xu, Huaxi; Wang, Shengjun

    2015-05-01

    VP1 protein is the immunodominant capsid protein of enterovirus 71 (EV71) which is responsible for large outbreaks of hand, foot and mouth disease. It has been reported that glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and its ligand (GITRL) are involved in modulating both innate and adaptive immune responses. In this study, a DNA vaccine vector encoding EV71 VP1 gene and mGITRL gene (pIRES/VP1/mGITRL) was constructed. And female Balb/c mice were immunized intramuscularly with the DNA vaccine. Compared with the groups immunized with pIRES, pIRES/VP1, pIRES/mGITRL and PBS, the inoculation of pIRES/VP1/mGITRL induced a higher levels of EV71 VP1-specific antibody and specific antibody-forming cells. However, significantly higher levels of CD4(+)Th1, Th2 and CD8(+)IFN-γ(+)T cells were found in the pIRES/VP1/mGITRL group compared with control groups. Our results demonstrate that a novel DNA vaccine, expressing VP1 and mGITRL, could effectively elicit both humoral and cell-mediated immune responses against EV71 VP1 in mice. Thus, the mGITRL may be used as molecular adjuvant for EV71 DNA vaccine. PMID:25772201

  1. Current and Historical Drivers of Landscape Genetic Structure Differ in Core and Peripheral Salamander Populations

    PubMed Central

    Dudaniec, Rachael Y.; Spear, Stephen F.; Richardson, John S.; Storfer, Andrew

    2012-01-01

    With predicted decreases in genetic diversity and greater genetic differentiation at range peripheries relative to their cores, it can be difficult to distinguish between the roles of current disturbance versus historic processes in shaping contemporary genetic patterns. To address this problem, we test for differences in historic demography and landscape genetic structure of coastal giant salamanders (Dicamptodon tenebrosus) in two core regions (Washington State, United States) versus the species' northern peripheral region (British Columbia, Canada) where the species is listed as threatened. Coalescent-based demographic simulations were consistent with a pattern of post-glacial range expansion, with both ancestral and current estimates of effective population size being much larger within the core region relative to the periphery. However, contrary to predictions of recent human-induced population decline in the less genetically diverse peripheral region, there was no genetic signature of population size change. Effects of current demographic processes on genetic structure were evident using a resistance-based landscape genetics approach. Among core populations, genetic structure was best explained by length of the growing season and isolation by resistance (i.e. a ‘flat’ landscape), but at the periphery, topography (slope and elevation) had the greatest influence on genetic structure. Although reduced genetic variation at the range periphery of D. tenebrosus appears to be largely the result of biogeographical history rather than recent impacts, our analyses suggest that inherent landscape features act to alter dispersal pathways uniquely in different parts of the species' geographic range, with implications for habitat management. PMID:22590604

  2. Specific Genetic Immunotherapy Induced by Recombinant Vaccine Alpha-Fetoprotein-Heat Shock Protein 70 Complex

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoping; Lin, Huanping; Wang, Qiaoxia

    Purposes: To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific CTL response and its protective effect against AFP-producing tumor. Material/Methods: A recombinant vaccine was constructed by conjugating mouse alpha-fetoprotein to heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-γ in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. Results: By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-γ and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50±11.70 IFN-γ spots/106 cells vs 41.60±10.40 IFN-γ spots/106 cells, 7.32±3.14 IFN-γ spots/106 cells, P<0.01; 156.32±10.42 μg/mL vs 66.52±7.35 μg/mL, 5.73±2.89 μg/mL, P<0.01). The tumor volume in mAFP/HSP70 group was significantly smaller than that in mAFP and HSP70 groups (42.44±7.14 mm3 vs 392.23±12.46 mm3, 838.63±13.84 mm3, P<0.01). Conclusions: The study further confirmed the function of heat shock protein 70's immune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for hepatocellular carcinoma.

  3. Interleukin-Encoding Adenoviral Vectors as Genetic Adjuvant for Vaccination against Retroviral Infection

    PubMed Central

    Ohs, Inga; Windmann, Sonja; Wildner, Oliver; Dittmer, Ulf; Bayer, Wibke

    2013-01-01

    Interleukins (IL) are cytokines with stimulatory and modulatory functions in the immune system. In this study, we have chosen interleukins which are involved in the enhancement of TH2 responses and B cell functions to analyze their potential to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to antibody and virus-specific CD4+ T cell responses. Mice were vaccinated with an adenoviral vector which encodes and displays the Friend Virus (FV) surface envelope protein gp70 (Ad.pIXgp70) in combination with adenoviral vectors encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with high control over FV-induced splenomegaly and reduced viral loads. Mice co-immunized with adenoviral vectors encoding IL5 or IL23 showed increased neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23 showed improved FV-specific CD4+ T cell responses compared to mice immunized with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors encoding specific interleukins is suitable to improve the vaccination efficacy of an anti-retroviral vaccine. Improved protection correlated with improved CD4+ T cell responses and especially with higher neutralizing antibody titers. The co-application of selected interleukin-encoding adenoviral vectors is a valuable tool for vaccination with regard to enhancement of antibody mediated immunity. PMID:24349306

  4. Rising Cellular Immune Response after Injection of pVax/iutA: A Genetic DNA Cassette as Candidate Vaccine against Urinary Tract Infection

    PubMed Central

    BAKHTIARI, Ronak; AHMADIAN, Shahin; FALLAH MEHRABADI, Jalil

    2016-01-01

    Background: Uropathogenic Escherichia coli (UPEC) are major bacterial agent of Urinary Tract Infection (UTI). This infection is more prevalent among women because approximately half of all women will experience a UTI in their life-time and near a quarter of them will have a recurrent infection within 6–12 months. IutA protein has a major role during UPEC pathogenesis and consequently infection. Therefore, the aim of current study was assessment of IutA protein roles as a potential candidate antigen based for vaccine designing. Methods: This survey was conducted during 2014–2015 at the University of Tehran, Iran. Chromosomal DNA extracted from E. coli 35218 and iutA gene amplified by PCR. The amplicon cloned to pVax.1 eukaryotic expression vector and recombinant vector confirmed by sequencing. The iutA gene expression in genetic cassette of pVax/iutA was evaluated in COS7 cell line by RT-PCR. Then, injected to mouse model, which divided to three groups: injected with pVax vector, PBS and pVax/iutA cassette respectively in two stages (d 1 and 14). One week after the second injection, bleeding from immunized mouse was performed and IFN-gamma was measured. Results: The mice immunized with pVax/iutA showed increased interferon-γ responses significantly higher than two non-immunized groups (P<0.05). Conclusion: Cellular immune response has a main protective role against UTI. Raising this kind of immune response is important to preventing of recurrent infection. Moreover, the current DNA cassette will be valuable for more trying to prepare a new vaccine against UTI. PMID:27516995

  5. DNA-antiviral vaccines: new developments and approaches--a review.

    PubMed

    Giese, M

    1998-01-01

    Current vaccines can be divided into "live," "recombinant" and "killed" vaccines. Live vaccines are traditionally composed of attenuated viruses or bacteria, selected for their reduced pathogenicity. Recombinant vaccines, driven by a viral or bacterial vector express foreign antigens, or only recombinant proteins injected as antigen. Killed vaccines consist of inactivated whole pathogens. But all these traditional vaccines have some disadvantages: Attenuated live vaccine are able to undergo mutation and as mutated viruses or bacteria can now provoke the diseases against which the vaccine should protect the organism. A further disadvantage of live vaccines is the possibility of shedding which is a real problem especially in veterinary medicine. Clearly, there is a need for better vaccines to protect against diseases without the disadvantages associated with vaccines presently in use. Modern vaccines might be characterized as safe, no risk of reversion to pathogenicity, and they should be stable without the necessity of a "cold chain." Production should be simple, standardized and inexpensive. Vaccine development has now been improved by the ability to use direct inoculations of plasmid DNA encoding viral or bacterial proteins. One of the major benefits of DNA-vaccines, variously termed "DNA-, genetic- or nucleic acid-immunization," is the endogenous synthesis of the encoded protein. Therefore DNA vaccines mimic natural infection and provoke both strong humoral and cellular immune response. This review summarizes new developments and approaches of DNA vaccination and explains the construction of expression plasmids as well as possible mechanisms of immune responses. PMID:9926398

  6. Current Status and Development of Vaccines and Other Biologics for Human Rabies Prevention.

    PubMed

    Rupprecht, Charles E; Nagarajan, Thirumeni; Ertl, Hildegund

    2016-06-01

    Rabies is a neglected viral zoonosis with the highest case fatality of any infectious disease. Pasteur's historical accomplishments during the late 19(th) century began the process of human vaccine development, continuing to evolve into the 21(st) century. Over the past 35 years, great improvements occurred in the production of potent tissue culture vaccines and the gradual removal from the market of unsafe nerve tissue products. Timely and appropriate administration of modern biologics virtually assures survivorship, even after severe exposures. Nevertheless, in the developing world, if not provided for free nationally, the cost of a single course of human prophylaxis exceeds the average monthly wage of the common worker. Beyond traditional approaches, recombinant, sub-unit and other novel methods are underway to improve the availability of safe, effective and more affordable rabies biologics. PMID:26796599

  7. MERS-CoV vaccine candidates in development: The current landscape.

    PubMed

    Modjarrad, Kayvon

    2016-06-01

    Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in more than 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of MERS-CoV have created an urgent need for effective public health countermeasures, paramount of which is an effective means of prevention through a vaccine or antibody prophylaxis. Despite the relatively few number of cases to-date, research and development of MERS-CoV vaccine candidates is advancing quickly. This review surveys the landscape of these efforts across multiple groups in academia, government and industry. PMID:27083424

  8. Salmonella Serogroup C: Current Status of Vaccines and Why They Are Needed.

    PubMed

    Fuche, Fabien J; Sow, Ousmane; Simon, Raphael; Tennant, Sharon M

    2016-09-01

    Nontyphoidal Salmonella (NTS; i.e., Salmonella enterica organisms that do not cause typhoid or paratyphoid) are responsible for 94 million infections and 155,000 deaths worldwide annually, 86% of which are estimated to be foodborne. Although more than 50 serogroups and 2,600 serovars have been described, not all Salmonella serovars cause disease in humans and animals. Efforts are being made to develop NTS vaccines, with most approaches eliciting protection against serovars Typhimurium and Enteritidis (serogroups B [O:4] and D [O:9], respectively), as they are widely considered the most prevalent. Here, we show that serogroup C (O:6,7, O:6,8, or O:8 epitopes) is the most common serogroup in the United States, and the prevalence of serovars from this serogroup has been increasing in Europe and the United States over the last decade. They are also the most commonly isolated serovars from healthy cattle and poultry, indicating the underlying importance of surveillance in animals. Four out of the 10 most lethal serovars in the United States are serogroup C, and reports from African countries suggest that strains within this serogroup are highly antibiotic resistant. Serogroup C consists of highly diverse organisms among which 37 serovars account for the majority of human cases, compared to 17 and 11 serovars for serogroups B and D, respectively. Despite these concerning data, no human vaccines targeting serogroup C NTS are available, and animal vaccines are in limited use. Here, we describe the underestimated burden represented by serogroup C NTS, as well as a discussion of vaccines that target these pathogens. PMID:27413069

  9. Current initiatives to protect Rhode Island adolescents through increasing HPV vaccination.

    PubMed

    Washburn, Tricia; Devi Wold, Anne; Raymond, Patricia; Duggan-Ball, Sue; Marceau, Kathy; Beardsworth, AnneMarie

    2016-06-01

    This commentary provides an overview of recent initiatives in Rhode Island to promote human papillomavirus (HPV) vac-30 cination with the goal of protecting Rhode Island adolescents against vaccine-preventable HPV-associated cancers. With the exception of the introduction of a recent school entry requirement, most of the initiatives and related activities described were conducted as part of a cooperative agreement between 35 RIDOH and CDC, and were supported by the Prevention and Public Health Fund. (1). PMID:27141954

  10. Genetics of Lafora progressive myoclonic epilepsy: current perspectives.

    PubMed

    Kecmanović, Miljana; Keckarević-Marković, Milica; Keckarević, Dušan; Stevanović, Galina; Jović, Nebojša; Romac, Stanka

    2016-01-01

    Lafora disease (LD) is a fatal neurodegenerative disorder caused by loss-of-function mutations in either laforin glycogen phosphatase gene (EPM2A) or malin E3 ubiquitin ligase gene (NHLRC1). LD is associated with gradual accumulation of Lafora bodies (LBs). LBs are aggregates of polyglucosan, a long, linear, poorly branched, hyperphosphorylated, insoluble form of glycogen. Loss-of-function mutations either in the EPM2A or in the NHLRC1 gene lead to polyglucosan formation. One hypothesis on LB formation is based on findings that laforin-malin complex downregulates glycogen synthase (GS) through malin-mediated ubiquitination, and the other one is based on findings that laforin dephosphorylates glycogen. According to the first hypothesis, polyglucosan formation is a result of increased GS activity, and according to the second, an increased glycogen phosphate leads to glycogen conformational change, unfolding, precipitation, and conversion to polyglucosan, while GS remains bound to the precipitating glycogen. In this review, we summarize all the recent findings that have important implications for the treatment of LD, all of them showing that partial inhibition of GS activity may be sufficient to prevent the progression of the disease. The current perspective in LD is high-throughput screening for small molecules that act on the disease pathway, that is, partial inhibitors of GS, which opens a therapeutic window for potential treatment of this fatal disease. PMID:27194917

  11. Genetics of Lafora progressive myoclonic epilepsy: current perspectives

    PubMed Central

    Kecmanović, Miljana; Keckarević-Marković, Milica; Keckarević, Dušan; Stevanović, Galina; Jović, Nebojša; Romac, Stanka

    2016-01-01

    Lafora disease (LD) is a fatal neurodegenerative disorder caused by loss-of-function mutations in either laforin glycogen phosphatase gene (EPM2A) or malin E3 ubiquitin ligase gene (NHLRC1). LD is associated with gradual accumulation of Lafora bodies (LBs). LBs are aggregates of polyglucosan, a long, linear, poorly branched, hyperphosphorylated, insoluble form of glycogen. Loss-of-function mutations either in the EPM2A or in the NHLRC1 gene lead to polyglucosan formation. One hypothesis on LB formation is based on findings that laforin–malin complex downregulates glycogen synthase (GS) through malin-mediated ubiquitination, and the other one is based on findings that laforin dephosphorylates glycogen. According to the first hypothesis, polyglucosan formation is a result of increased GS activity, and according to the second, an increased glycogen phosphate leads to glycogen conformational change, unfolding, precipitation, and conversion to polyglucosan, while GS remains bound to the precipitating glycogen. In this review, we summarize all the recent findings that have important implications for the treatment of LD, all of them showing that partial inhibition of GS activity may be sufficient to prevent the progression of the disease. The current perspective in LD is high-throughput screening for small molecules that act on the disease pathway, that is, partial inhibitors of GS, which opens a therapeutic window for potential treatment of this fatal disease. PMID:27194917

  12. A new genetic vaccine platform based on an adeno-associated virus isolated from a rhesus macaque.

    PubMed

    Lin, Jianping; Calcedo, Roberto; Vandenberghe, Luk H; Bell, Peter; Somanathan, Suryanarayan; Wilson, James M

    2009-12-01

    We created a hybrid adeno-associated virus (AAV) from two related rhesus macaque isolates, called AAVrh32.33, and evaluated it as a vaccine carrier for human immunodeficiency virus type 1 (HIV-1) and type A influenza virus antigens. The goal was to overcome the limitations of vaccines based on other AAVs, which generate dysfunctional T-cell responses and are inhibited by antibodies found in human sera. Injection of a Gag-expressing AAVrh32.33 vector into mice resulted in a high-quality CD8(+) T-cell response. The resulting Gag-specific T cells express multiple cytokines at high levels, including interleukin-2, with many having memory phenotypes; a subsequent boost with an adenovirus vector yielded a brisk expansion of Gag-specific T cells. A priming dose of AAVrh32.33 led to high levels of Gag antibodies, which exceed levels found after injection of adenovirus vectors. Importantly, passive transfer of pooled human immunoglobulin into mice does not interfere with the efficacy of AAVrh32.33 expressing nucleoproteins from influenza virus, as measured by protection to a lethal dose of influenza virus, which is consistent with the very low seroprevalence to this virus in humans. Studies of macaques with vectors expressing gp140 from HIV-1 (i.e., with AAVrh32.33 as the prime and simian adenovirus type 24 as the boost) demonstrated results similar to those for mice with high-level and high-quality CD8(+) T-cell responses to gp140 and high-titered neutralizing antibodies to homologous HIV-1. The biology of this novel AAV hybrid suggests that it should be a preferred genetic vaccine carrier, capable of generating robust T- and B-cell responses. PMID:19812149

  13. Delivery of DNA vaccines by agarose hydrogel implants facilitates genetic immunization in cattle.

    PubMed

    Toussaint, J F; Dubois, A; Dispas, M; Paquet, D; Letellier, C; Kerkhofs, P

    2007-01-26

    The present study demonstrates the interest of two slow-release systems as vaccination tools in cattle. Two experiments show that a first intradermal administration of one DNA vaccine dose combined with the slow-release of a second dose conduct to a priming of the bovine herpesvirus 1-specific immune response similar to the one generated by two discrete administrations 4 weeks apart. The first experiment demonstrates the efficacy of the slow-release system with well-characterized Alzet osmotic pumps, whereas the second experiment extends the same concept with innovative agarose hydrogel implants. These latter implants are cheaper and more convenient than the osmotic pumps or repeated intradermal administrations since they contribute to an efficient priming of the immune response in a single manipulation of the animals. PMID:17084488

  14. Genetic Diversity of the Malaria Vaccine Candidate Plasmodium falciparum Merozoite Surface Protein-3 in a Hypoendemic Transmission Environment

    PubMed Central

    Jordan, Stephen J.; Branch, OraLee H.; Castro, Jean Carlos; Oster, Robert A.; Rayner, Julian C.

    2009-01-01

    The N-terminal domain of Plasmodium falciparum merozoite surface protein-3 (PfMSP3) has been excluded from malaria vaccine development largely because of genetic diversity concerns. However, no study to date has followed N-terminal diversity over time. This study describes PfMSP3 variation in a hypoendemic longitudinal cohort in the Peruvian Amazon over the 2003-2006 transmission seasons. Polymerase chain reaction was used to amplify the N-terminal domain in 630 distinct P. falciparum infections, which were allele-typed by size and also screened for sequence variation using a new high-throughput technique, denaturing high performance liquid chromatography. PfMSP3 allele frequencies fluctuated significantly over the 4-year period, but sequence variation was very limited, with only 10 mutations being identified of 630 infections screened. The sequence of the PfMSP3 N-terminal domain is relatively stable over time in this setting, and further studies of its status as a vaccine candidate are therefore warranted. PMID:19270302

  15. Current barriers, challenges and opportunities for the development of effective STI vaccines: point of view of vaccine producers, biotech companies and funding agencies.

    PubMed

    Dodet, Betty

    2014-03-20

    Several barriers limit the development of vaccines against sexually transmitted diseases (STIs). Critical scientific information is missing that makes the feasibility and the likelihood of success of vaccines against genital herpes, chlamydia, gonorrhea and trichomonas uncertain: the immunity induced by natural infection is absent or imperfect which seriously limits the capacity to define the types of immune responses that an effective vaccine must induce. Reliable animal models are lacking and a number of crucial clinical questions are still unanswered about the goal of these vaccines and definition of endpoints for clinical trials. In the absence of a clear recognition of the need for vaccines against these diseases, there is no motivation for public or private research and industry to invest in the development of vaccines against STIs. The STI burden should be evaluated not only in terms of mortality and morbidity, but also in terms of economic and psycho-social impact. A global public-private consortium could mobilize the joint efforts of all stakeholders involved in the research, development and implementation of STI vaccines of the public and private sectors; ensure that sufficient resources are applied to R&D of vaccines against these STIs; and provide the pull-push forces that are necessary to overcome the barriers to develop safe and effective vaccines against these diseases. PMID:23994377

  16. Dengue vaccine

    PubMed Central

    Jindal, Harashish; Bhatt, Bhumika; Malik, Jagbir Singh; SK, Shashikantha

    2014-01-01

    Dengue has emerged as one of the major global public health problems. The disease has broken out of its shell and has spread due to increased international travel and climatic changes. Globally, over 2.5 billion people accounting for >40% of the world's population are at risk from dengue. Since the 1940s, dengue vaccines have been under investigation. A live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue virus (CYD-TDV) has progressed to phase III efficacy studies. Dengue vaccine has been found to be a cost-effective intervention to reduce morbidity and mortality. Current dengue vaccine candidates aim to protect against the 4 dengue serotypes, but the recent discovery of a fifth serotype could complicate vaccine development. In recent years, an urgent need has been felt for a vaccine to prevent the morbidity and mortality from this disease in a cost-effective way. PMID:25424928

  17. Blinders, phenotype, and fashionable genetic analysis: a critical examination of the current state of epilepsy genetic studies.

    PubMed

    Greenberg, David A; Subaran, Ryan

    2011-01-01

    Although it is accepted that idiopathic generalized epilepsy (IGE) is strongly, if not exclusively, influenced by genetic factors, there is little consensus on what those genetic influences may be, except for one point of agreement: epilepsy is a "channelopathy." This point of agreement has continued despite the failure of studies investigating channel genes to demonstrate the primacy of their influence on IGE expression. The belief is sufficiently entrenched that the more important issues involving phenotype definition, data collection, methods of analysis, and the interpretation of results have become subordinate to it. The goal of this article is to spark discussion of where the study of epilepsy genetics has been and where it is going, suggesting we may never get there if we continue on the current road. We use the long history of psychiatric genetic studies as a mirror and starting point to illustrate that only when we expand our outlook on how to study the genetics of the epilepsies, consider other mechanisms that could lead to epilepsy susceptibility, and, especially, focus on the critical problem of phenotype definition, will the major influences on common epilepsy begin to be understood. PMID:21219301

  18. Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses

    PubMed Central

    Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nuntawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

    2012-01-01

    Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate (A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby Canine Kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 29 HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. PMID:22230579

  19. Host Genetic Determinants of T Cell Responses to the MRKAd5 HIV-1 gag/pol/nef Vaccine in the Step Trial

    PubMed Central

    Fellay, Jacques; Frahm, Nicole; Shianna, Kevin V.; Cirulli, Elizabeth T.; Casimiro, Danilo R.; Robertson, Michael N.; Haynes, Barton F.; Geraghty, Daniel E.; McElrath, M. Juliana

    2011-01-01

    Understanding how human genetic variation impacts individual response to immunogens is fundamental for rational vaccine development. To explore host mechanisms involved in cellular immune responses to the MRKAd5 human immunodeficiency virus type 1 (HIV-1) gag/pol/nef vaccine tested in the Step trial, we performed a genome-wide association study of determinants of HIV-specific T cell responses, measured by interferon γ enzyme-linked immunospot assays. No human genetic variant reached genome-wide significance, but polymorphisms located in the major histocompatibility complex (MHC) region showed the strongest association with response to the HIV-1 Gag protein: HLA-B alleles known to be associated with differences in HIV-1 control were responsible for these associations. The implication of the same HLA alleles in vaccine-induced cellular immunity and in natural immune control is of relevance for vaccine design. Furthermore, our results demonstrate the importance of considering the host immunogenetic background in the analysis of immune responses to T cell vaccines. PMID:21278214

  20. Schistosomiasis vaccines

    PubMed Central

    Siddiqui, Bilal A.; Ganley-Leal, Lisa

    2011-01-01

    Schistosomiasis is a major neglected tropical disease of public health importance to a billion people. An estimated 200 million people are currently infected; an additional 779 million individuals are at risk to acquire the infection in 74 countries. Despite many years of implementation of mass anti-parasitic drug therapy programs and other control measures, this disease has not been contained and continues to spread to new geographic areas.  The discovery of a protective vaccine still remains the most potentially effective means for the control of this disease, especially if the vaccine provides long-term immunity against the infection. A vaccine would contribute to the reduction of schistosomiasis morbidity through induced immune responses leading to decrease in parasite load and reduced egg production. This vaccine could be administered to children between the ages of 3 and 12 years to prevent severe infection in a particularly high risk population. This review summarizes the current status of schistosomiasis vaccine development. PMID:22048120

  1. Genetically modified rabies virus ERA strain is safe and induces long-lasting protective immune response in dogs after oral vaccination.

    PubMed

    Shuai, Lei; Feng, Na; Wang, Xijun; Ge, Jinying; Wen, Zhiyuan; Chen, Weiye; Qin, Lide; Xia, Xianzhu; Bu, Zhigao

    2015-09-01

    Oral immunization in free-roaming dogs is one of the most practical approaches to prevent rabies for developing countries. The safe, efficient and long-lasting protective oral rabies vaccine for dogs is highly sought. In this study, rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain wild-type (rERA) and a genetically modified type (rERAG333E) containing a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) were generated by reverse genetic. The recombinant virus rERAG333E retained growth properties of similar to the parent strain rERA in BHK-21 cell culture. The G333E mutation showed genetic stability during passage into neuroblastoma cells and in the brains of suckling mice and was significantly reduced the virulence of rERA in mice. rERAG333E was immunogenic in dogs by intramuscular inoculation. Mice orally vaccinated with rERAG333E induced strong and one year longer virus neutralizing antibodies (VNA) to RABV, and were completely protected from challenge with lethal street virus at 12months after immunization. Dogs received oral vaccination with rERAG333E induced strong protective RABV VNA response, which lasted for over 3years, and moderate saliva RABV-specific IgA. Moreover, sizeable booster responses to RABV VNA were induced by a second oral dose 1year after the first dose. These results demonstrated that the genetically modified ERA vaccine strain has the potential to serve as a safe and efficient oral live vaccine against rabies in dogs. PMID:26093157

  2. [Autoimmune connective tissue diseases and vaccination].

    PubMed

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-01-01

    The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group. PMID:27259225

  3. Landscape genetics of raccoons (Procyon lotor) associated with ridges and valleys of Pennsylvania: implications for oral rabies vaccination programs.

    PubMed

    Root, J Jeffrey; Puskas, Robert B; Fischer, Justin W; Swope, Craig B; Neubaum, Melissa A; Reeder, Serena A; Piaggio, Antoinette J

    2009-12-01

    Raccoons are the reservoir for the raccoon rabies virus variant in the United States. To combat this threat, oral rabies vaccination (ORV) programs are conducted in many eastern states. To aid in these efforts, the genetic structure of raccoons (Procyon lotor) was assessed in southwestern Pennsylvania to determine if select geographic features (i.e., ridges and valleys) serve as corridors or hindrances to raccoon gene flow (e.g., movement) and, therefore, rabies virus trafficking in this physiographic region. Raccoon DNA samples (n = 185) were collected from one ridge site and two adjacent valleys in southwestern Pennsylvania (Westmoreland, Cambria, Fayette, and Somerset counties). Raccoon genetic structure within and among these study sites was characterized at nine microsatellite loci. Results indicated that there was little population subdivision among any sites sampled. Furthermore, analyses using a model-based clustering approach indicated one essentially panmictic population was present among all the raccoons sampled over a reasonably broad geographic area (e.g., sites up to 36 km apart). However, a signature of isolation by distance was detected, suggesting that widths of ORV zones are critical for success. Combined, these data indicate that geographic features within this landscape influence raccoon gene flow only to a limited extent, suggesting that ridges of this physiographic system will not provide substantial long-term natural barriers to rabies virus trafficking. These results may be of value for future ORV efforts in Pennsylvania and other eastern states with similar landscapes. PMID:19125658

  4. RETRACTION of "Immune memory responses to HBV vaccine 13-18 years after primary vaccination" by L. Hou, W. Li, X. Wei, Y. Zhou, Y. Zhuo, H. Wu, B. Shen. Genet. Mol. Res. 14 (3): 8466-8472 (2015).

    PubMed

    Hou, L; Li, W; Wei, X; Zhou, Y; Zhuo, Y; Wu, H; Shen, B

    2016-01-01

    The article "Immune memory responses to HBV vaccine 13-18 years after primary vaccination" by L. Hou, W. Li, X. Wei, Y. Zhou, Y. Zhuo, H. Wu, B. Shen published in 2015 in Genetics and Molecular Research 14(3): 8466-8472 (http://dx.doi.org/10.4238/2015.July.28.14) has been found to be substantially equal to the article "Immune memory response induced in vitro by recombinant hepatitis B surface antigen challenge 13-18 years after primary vaccination" published in the Journal of Medical Virology 86:1700-1704 (2014) from Andrea do Livramento et al. (DOI: 10.1002/jmv.24012). The corresponding author of the article published in Genetics and Molecular Research, Baosheng Shen, alerted our editorial staff about this situation and requested the retraction of the article. The Publisher and Editor retract this article in Accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation, we have strong reasons to believe que the peer review process was failure and after review and contacting the authors, the editors of Genetics and Molecular Research have decided to retract the article. The authors and their institutions have been advised of this serious breach of ethics. PMID:26985925

  5. Improving medical students’ knowledge of genetic disease: a review of current and emerging pedagogical practices

    PubMed Central

    Wolyniak, Michael J; Bemis, Lynne T; Prunuske, Amy J

    2015-01-01

    Genetics is an essential subject to be mastered by health professional students of all types. However, technological advances in genomics and recent pedagogical research have changed the way in which many medical training programs teach genetics to their students. These advances favor a more experience-based education focused primarily on developing student’s critical thinking skills. In this review, we examine the current state of genetics education at both the preclinical and clinical levels and the ways in which medical and pedagogical research have guided reforms to current and emerging teaching practices in genetics. We discover exciting trends taking place in which genetics is integrated with other scientific disciplines both horizontally and vertically across medical curricula to emphasize training in scientific critical thinking skills among students via the evaluation of clinical evidence and consultation of online databases. These trends will produce future health professionals with the skills and confidence necessary to embrace the new tools of medical practice that have emerged from scientific advances in genetics, genomics, and bioinformatics. PMID:26604852

  6. Improving medical students' knowledge of genetic disease: a review of current and emerging pedagogical practices.

    PubMed

    Wolyniak, Michael J; Bemis, Lynne T; Prunuske, Amy J

    2015-01-01

    Genetics is an essential subject to be mastered by health professional students of all types. However, technological advances in genomics and recent pedagogical research have changed the way in which many medical training programs teach genetics to their students. These advances favor a more experience-based education focused primarily on developing student's critical thinking skills. In this review, we examine the current state of genetics education at both the preclinical and clinical levels and the ways in which medical and pedagogical research have guided reforms to current and emerging teaching practices in genetics. We discover exciting trends taking place in which genetics is integrated with other scientific disciplines both horizontally and vertically across medical curricula to emphasize training in scientific critical thinking skills among students via the evaluation of clinical evidence and consultation of online databases. These trends will produce future health professionals with the skills and confidence necessary to embrace the new tools of medical practice that have emerged from scientific advances in genetics, genomics, and bioinformatics. PMID:26604852

  7. Importance of vaccination habit and vaccine choice on influenza vaccination among healthy working adults.

    PubMed

    Lin, Chyongchiou J; Nowalk, Mary Patricia; Toback, Seth L; Rousculp, Matthew D; Raymund, Mahlon; Ambrose, Christopher S; Zimmerman, Richard K

    2010-11-10

    This randomized cluster trial was designed to improve workplace influenza vaccination rates using enhanced advertising, choice of vaccine type (intranasal or injectable) and an incentive. Workers aged 18-49 years were surveyed immediately following vaccination to determine factors associated with vaccination behavior and choice. The questionnaire assessed attitudes, beliefs and social support for influenza vaccine, demographics, and historical, current, and intentional vaccination behavior. Of the 2389 vaccinees, 83.3% received injectable vaccine and 16.7% received intranasal vaccine. Factors associated with previous influenza vaccination were older age, female sex, higher education and greater support for injectable vaccine (all P<.02). Current influenza vaccination with intranasal vaccine vs. injectable vaccine was associated with higher education, the study interventions, greater support for the intranasal vaccine and nasal sprays, less support of injectable vaccine, more negative attitudes about influenza vaccine, and a greater likelihood of reporting that the individual would not have been vaccinated had only injectable vaccine been offered (all P<.01). Intentional vaccine choice was most highly associated with previous vaccination behavior (P<.001). A key to long term improvements in workplace vaccination is to encourage first time influenza vaccination through interventions that include incentives, publicity and vaccine choice. PMID:20638452

  8. The Genetic Basis of Peripheral Arterial Disease: Current Knowledge, Challenges and Future Directions

    PubMed Central

    Kullo, Iftikhar J.; Leeper, Nicholas J.

    2015-01-01

    Several risk factors for atherosclerotic peripheral arterial disease (PAD) such as dyslipidemia, diabetes and hypertension, are heritable. However, predisposition to PAD may be influenced by genetic variants acting independently of these risk factors. Identification of such genetic variants will provide insights into underlying pathophysiologic mechanisms and facilitate the development of novel diagnostic and therapeutic approaches. In contrast to coronary heart disease, relatively few genetic variants that influence susceptibility to PAD have been discovered. This may be in part due to greater clinical and genetic heterogeneity in PAD. In this review, we a) provide an update on the current state of knowledge about the genetic basis of PAD including results of family studies and candidate gene, linkage as well as genome-wide association studies; b) highlight the challenges in investigating the genetic basis of PAD and possible strategies to overcome these challenges; and c) discuss the potential of genome sequencing, RNA sequencing, differential gene expression, epigenetic profiling and systems biology in increasing our understanding of the molecular genetics of PAD. PMID:25908728

  9. Current Developments in the Genetics of Autism: From Phenome to Genome

    PubMed Central

    Sullivan, Patrick F.; Trembath, Dimitri; Piven, Joseph

    2009-01-01

    Despite compelling evidence from twin and family studies indicating a strong genetic involvement in the etiology of autism, the unequivocal detection of autism susceptibility genes remains an elusive goal. The purpose of this review is to evaluate the current state of autism genetics research, with attention focused on new techniques and analytic approaches. We first present a brief overview of evidence for the genetic basis of autism, followed by an appraisal of linkage and candidate gene study findings and consideration of new analytic approaches to the study of complex psychiatric conditions, namely, genome-wide association studies, assessment of structural variation within the genome, and the incorporation of endophenotypes in genetic analysis. PMID:18716561

  10. Glycan surface antigens from Bacillus anthracis as vaccine targets: current status and future perspectives.

    PubMed

    Adamo, Roberto

    2014-07-01

    Over recent years great attention has been directed to the discovery of novel antigens from Bacillus anthracis, because of the potential of its spores in the development of weapons for mass destruction. Substantial effort has been directed to the identification and immunochemical evaluation of glycans that might be used for specific diagnostic detection of the spores or immune-mediated prevention of anthrax. Carbohydrate structures found on surfaces of vegetative cells and spores are herein discussed. Among them, the cell wall polysaccharide and the tetrasaccharide unit isolated from the exosporium protein BclA were proven immunogenic in an animal model after covalent linkage to carrier protein. Further investigation is needed to fully assess the potential of these promising carbohydrate antigens for vaccine development. PMID:24867680

  11. Evidence-based vaccination strategies in obstetrics and gynecology settings: Current practices and methods for assessment.

    PubMed

    O'Leary, Sean T; Pyrzanowski, Jennifer; Brewer, Sarah E; Dickinson, L Miriam; Dempsey, Amanda F

    2016-04-01

    Obstetrician-gynecologists have the potential to play an important role in the delivery of immunizations to women. However, despite national recommendations, immunization rates among pregnant women and adults in general remain low. Pragmatic immunization delivery trials are needed to demonstrate how best to deliver vaccines in such settings. We report the development and implementation of 2 novel methodologies for immunization delivery research and quality improvement in such settings. The first was the development and application of a 47-point Immunization Delivery Scale that formally assessed variability among practices in their engagement in a variety of evidence-based practices for improving immunization rates. The second was a covariate-constrained randomization technique - a method for achieving balance between study arms in cluster-randomized trials that is especially applicable to pragmatic trials.. To best achieve meaningful and interpretable findings, we recommend use of these or similar techniques in future immunization research and quality improvement projects in OB/GYN settings. PMID:26829978

  12. Rationale and prospects for novel pneumococcal vaccines.

    PubMed

    Moffitt, Kristin; Malley, Richard

    2016-01-01

    Streptococcus pneumoniae remains one of the most frequent bacterial causes of morbidity and mortality worldwide. National immunization programs implementing pneumococcal polysaccharide conjugate vaccines (PCVs) have successfully reduced rates of vaccine-type invasive disease and colonization both via direct effects in immunized children and, in some settings, indirect effects in unimmunized individuals. Limitations of the current PCV approach include the emergence of non-vaccine serotypes contributing to carriage and invasive disease in high-PCV coverage settings and the high cost of goods of PCVs which limits their accessibility in developing countries where the burden of disease remains highest. Furthermore, the distribution of serotypes causing disease varies geographically and includes more serotypes than are currently covered in a single PCV formulation. Researchers have long been exploring the potential of genetically conserved non-capsular pneumococcal antigens as vaccine candidates that might overcome such limitations. To better evaluate the rationale of such approaches, an understanding of the mechanisms of immunity to the various phases of pneumococcal infection is of paramount importance. Herein we will review the evolving understanding of both vaccine-induced and naturally acquired immunity to pneumococcal colonization and infection and discuss how this informs current approaches using serotype-independent pneumococcal vaccine candidates. We will then review the alternative vaccine candidates that have been or are currently under evaluation in clinical trials. PMID:26535755

  13. A practical validation approach for virus titer testing of avian infectious bursal disease live vaccine according to current regulatory guidelines.

    PubMed

    Weber Sušanj, Mirta; Košiček, Miljenko; Krnić, Ela Kosor; Ballarin-Perharić, Alenka; Terzić, Svjetlana

    2012-01-01

    The method for virus titer determination of avian infectious bursal disease (IBD) live vaccine, developed long before regulatory validation guidelines is a cell culture based biological assay intended for use in vaccine release testing. The aim of our study was to perform a validation, based on fit-for-purpose principle, of an old 50% tissue culture infectious dose (TCID(50)) method according to Guidelines of the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH). This paper addresses challenges and discusses some key aspects that should be considered when validating biological methods. A different statistical approach and non-parametric statistics was introduced in validation protocol in order to derive useful information from experimental data. This approach is applicable for a wide range of methods. In conclusion, the previous virus titration method had showed to be precise, accurate, linear, robust and in accordance with current regulatory standards, which indicates that there is no need for additional re-development or upgrades of the method for its suitability for intended use. PMID:21996052

  14. Rotavirus vaccines.

    PubMed

    Barnes, G

    1998-01-01

    Encouraging results have been reported from several large trials of tetravalent rhesus rotavirus vaccine, with efficacy of 70-80% against severe disease. A recent Venezuelan study showed similar results to trials in USA and Europe. The vaccine may soon be licensed in USA. It provides the exciting prospect of a strategy to prevent one of the world's major child killers. Other candidate vaccines are under development including human-bovine reassortants, neonatal strains, non-replicating rotaviruses, vector vaccines and other genetically engineered products. Second and third generation rotavirus vaccines are on the horizon. The need for a rotavirus vaccine is well accepted by paediatricians, but public health authorities need to be lobbied. Other issues which need to be addressed include relative importance of non-group A rotaviruses, possible administration with OPV, the influence of breast feeding, and most importantly, cost. It is essential that rotavirus vaccine is somehow made available to all of the world's children, not just those in developed countries. PMID:9553287

  15. Influenza Vaccines: Challenges and Solutions

    PubMed Central

    Houser, Katherine; Subbarao, Kanta

    2015-01-01

    Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291

  16. Use of a genetically defined double mutant strain of Bordetella bronchiseptica lacking adenylate cyclase and type III secretion as a live vaccine.

    PubMed

    Mann, Paul; Goebel, Elizabeth; Barbarich, James; Pilione, Mylisa; Kennett, Mary; Harvill, Eric

    2007-07-01

    While most vaccines consisting of killed bacteria induce high serum antibody titers, they do not always confer protection as effective as that induced by infection, particularly against mucosal pathogens. Bordetella bronchiseptica is a gram-negative respiratory pathogen that is endemic in many nonhuman mammalian populations and causes substantial disease in a variety of animals. At least 14 different live attenuated vaccines against this pathogen are available for use in a variety of livestock and companion animals. However, there are few published data on the makeup or efficacy of these vaccines. Here we report the use of a genetically engineered double mutant of B. bronchiseptica, which lacks adenylate cyclase and type III secretion, as a vaccine candidate. This strain is safe at high doses, even for highly immunocompromised animals, and induces immune responses that are protective against highly divergent B. bronchiseptica strains, preventing colonization in the lower respiratory tract and decreasing the bacterial burden in the upper respiratory tract. This novel B. bronchiseptica vaccine candidate induces strong local immunity while eliminating damage caused by the two predominant cytotoxic mechanisms. PMID:17452472

  17. Current and potential immune therapies and vaccines in the management of psoriasis

    PubMed Central

    Kaffenberger, Benjamin H; Lee, Grace L; Tyler, Kelly; Chan, Derek V; Jarjour, Wael; Ariza, Maria E; Williams, Marshall V; Wong, Henry K

    2014-01-01

    Psoriasis is a chronic, immune skin disease associated with significant morbidity. Development of psoriasis is influenced by numerous genes, one allele is HLA-CW*0602. Other genes and single nucleotide polymorphisms affect immunologic pathways and antimicrobial peptide synthesis. Dendritic cells initiate psoriasis by activating T-cells toward a Th1 and Th17 response, with increased cytokines including TNF-α, IL-6, -12, -17, -22, and -23. IL-22 appears to promote keratinocyte dedifferentiation and increased antimicrobial peptide synthesis while TNF-α and IL-17 induce leukocyte localization within the psoriatic plaque. These recent insights identifying key cytokine pathways have led to the development of inhibitors with significant efficacy in the treatment of psoriasis. While a strategy for vaccine modulation of the immune response in psoriasis is in progress, with new technology they may provide a cost-effective long-term treatment that may induce tolerance or targeted self-inhibition for patients with autoimmune disorders, such as psoriasis. PMID:24492530

  18. Current hepatitis B virus infection situation in Indonesia and its genetic diversity

    PubMed Central

    Lusida, Maria Inge; Juniastuti; Yano, Yoshihiko

    2016-01-01

    Indonesia has a moderate to high endemicity of hepatitis B virus (HBV) infection. The risk for chronic HBV infection is highest among those infected during infancy. Since 1997, hepatitis B (HepB) vaccination of newborns has been fully integrated into the National Immunization Program. Although HBV infection has been reduced by the universal newborn HepB immunization program, it continues to occur in Indonesia. The low birth dose coverage and the presence of vaccine escape mutants might contribute to this endemicity among children. Although limited information is available for an analysis of occult HBV infection (OBI), several variations and substitutions in the pre-S/S region have been detected in Indonesian HBV strains. Additionally, persistent infection and disease progression of chronic hepatitis B are related to not only viral factors but also the host genome. Indonesia is one of the most ethnically heterogeneous nations, with Javanese and Sundanese as the two highest ethnic groups. This multi-ethnicity makes genomic research in Indonesia difficult. In this article, we focused on and reviewed the following aspects: the current hepatitis B immunization program and its efficacy, OBI, HBV infection among high-risk patients, such as hemodialysis patients, and research regarding the host genome in Indonesia. PMID:27621573

  19. Current hepatitis B virus infection situation in Indonesia and its genetic diversity.

    PubMed

    Lusida, Maria Inge; Juniastuti; Yano, Yoshihiko

    2016-08-28

    Indonesia has a moderate to high endemicity of hepatitis B virus (HBV) infection. The risk for chronic HBV infection is highest among those infected during infancy. Since 1997, hepatitis B (HepB) vaccination of newborns has been fully integrated into the National Immunization Program. Although HBV infection has been reduced by the universal newborn HepB immunization program, it continues to occur in Indonesia. The low birth dose coverage and the presence of vaccine escape mutants might contribute to this endemicity among children. Although limited information is available for an analysis of occult HBV infection (OBI), several variations and substitutions in the pre-S/S region have been detected in Indonesian HBV strains. Additionally, persistent infection and disease progression of chronic hepatitis B are related to not only viral factors but also the host genome. Indonesia is one of the most ethnically heterogeneous nations, with Javanese and Sundanese as the two highest ethnic groups. This multi-ethnicity makes genomic research in Indonesia difficult. In this article, we focused on and reviewed the following aspects: the current hepatitis B immunization program and its efficacy, OBI, HBV infection among high-risk patients, such as hemodialysis patients, and research regarding the host genome in Indonesia. PMID:27621573

  20. Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

    PubMed Central

    2011-01-01

    uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection. Conclusion Infections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines. PMID:21749691

  1. Reverse genetics based rgH5N2 vaccine provides protection against high dose challenge of H5N1 avian influenza virus in chicken.

    PubMed

    Bhatia, S; Khandia, R; Sood, R; Bhat, S; Siddiqui, A; Jahagirdhar, G; Mishra, S; Mishra, A; Pateriya, A K; Kulkarni, D D

    2016-08-01

    An inactivated vaccine was developed using the rgH5N2 virus (6 + 2 reassortant) generated by plasmid based reverse genetics system (RGS) with WSN/33/H1N1 as backbone virus. Following mutation of the basic amino acid cleavage site RRRKKR*GLF to IETR*GLF, the H5-HA (haemagglutinin) gene of the selected donor H5N1 virus (A/chicken/West Bengal/80995/2008) of antigenic clade 2.2 was used along with the N2-NA gene from H9N2 field isolate (A/chicken/Uttar Pradesh/2543/2004) for generation of the rgH5N2 virus. A single dose (0.5 ml/bird) of the inactivated rgH5N2 vaccine protected 100% of the vaccinated chickens (n = 10) on 28(th) dpv (early challenge) and 90% of the vaccinated chickens (n = 10) on 200(th) dpv (late challenge) against high dose challenge with HPAI virus (10(9) EID50/bird). Challenge virus shedding via oropharynx and cloaca of the vaccinated chickens was detectable by realtime RT-PCR during 1-5 dpc and 1-9 days dpc in the early and the late challenge, respectively. The protective level of antibodies (mean HI titre > 128) was maintained without booster vaccination for 200 days. The present study provides the experimental evidence about the extent of protection provided by a reverse genetics based vaccine for clade 2.2 H5N1 viruses against challenge with high dose of field virus at two different time points (28 dpv and 200 dpv). The challenge study is uniquely different from the previous similar experiments on account of 1000 times higher dose of challenge and protection at 200 dpv. The protection and virus shedding data of the study may be useful for countries planning to use H5 vaccine in poultry especially against the clade 2.2 H5N1 viruses. PMID:27296706

  2. Live bacterial vaccines – a review and identification of potential hazards

    PubMed Central

    Detmer, Ann; Glenting, Jacob

    2006-01-01

    The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development. PMID:16796731

  3. Modern Advances in Genetic Testing: Ethical Challenges and Training Implications for Current and Future Psychologists

    PubMed Central

    Richmond-Rakerd, Leah S.

    2014-01-01

    The ethical implications for psychological practice of genetic testing are largely unexplored. Predictive testing can have a significant impact on health and well-being, and increasing numbers of individuals with knowledge of their risk for various disorders are likely to present for psychotherapy. In addition, more people will struggle with the decision of whether to obtain information regarding their genetic material. Psychologists will need to have the appropriate knowledge and clinical skills to effectively counsel this population. This article highlights the relevant ethical issues surrounding psychological treatment of individuals pursuing or considering undergoing genetic testing. These issues are extended to psychologists working in research, education, and policy domains. Recommendations for graduate training programs to facilitate current and future practitioner competence are also discussed. PMID:24707160

  4. Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature

    PubMed Central

    Sarlos, Patricia; Kovesdi, Erzsebet; Magyari, Lili; Banfai, Zsolt; Szabo, Andras; Javorhazy, Andras; Melegh, Bela

    2014-01-01

    Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammation-related genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility. PMID:25133031

  5. Nonclinical Development of BCG Replacement Vaccine Candidates.

    PubMed

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J

    2013-01-01

    The failure of current Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines. PMID:26343962

  6. Nonclinical Development of BCG Replacement Vaccine Candidates

    PubMed Central

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H.E.; Fulkerson, John; Brennan, Michael J.

    2013-01-01

    The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines. PMID:26343962

  7. [Vaccine application of recombinant herpesviruses].

    PubMed

    Yokoyama, N; Xuan, X; Mikami, T

    2000-04-01

    Recently, genetic engineering using recombinant DNA techniques has been applied to design new viral vaccines in order to reduce some problems which the present viral vaccines have. Up to now, many viruses have been investigated for development of recombinant attenuated vaccines or live viral vectors for delivery of foreign genes coding immunogenic antigens. In this article, we introduced the new vaccine strategy using genetically engineered herpesviruses. PMID:10774221

  8. Rotavirus vaccine: a review.

    PubMed

    Kumar, Goel Manish; Arun, Kumar; Bilas, Jain Ram; Ruchi, Jain; Pardeep, Khanna; Pradeep, Siwach

    2012-12-01

    Worldwide, large proportion i.e., 37% of deaths due to diarrhea in young children is attributed to rotavirus. A monovalent P1A[8] G1 vaccine and a pentavalent bovine-human reassortant vaccine human rotavirus vaccine had shown good clinical efficacy without any increase in intussusception among vaccine recipients. WHO recommends that the first dose of rotavirus vaccine should be administered to infants up to age of 6-15 weeks irrespective of the prior history of rotavirus infection and the maximum age for administering the last dose of the vaccine should be 32 weeks. Booster doses are not recommended. The current update reviews the issues related to rotavirus vaccines and their usages like milestones in the development of rotavirus vaccines, concerns regarding their efficacy and cost-effectiveness, immunity after natural infection, potential for changes in virus strains, current recommendations, post marketing surveillance, and future challenges and scope for further research regarding rotavirus vaccines. PMID:25145068

  9. Ancient Humans Influenced the Current Spatial Genetic Structure of Common Walnut Populations in Asia.

    PubMed

    Pollegioni, Paola; Woeste, Keith E; Chiocchini, Francesca; Del Lungo, Stefano; Olimpieri, Irene; Tortolano, Virginia; Clark, Jo; Hemery, Gabriel E; Mapelli, Sergio; Malvolti, Maria Emilia

    2015-01-01

    Common walnut (Juglans regia L) is an economically important species cultivated worldwide for its wood and nuts. It is generally accepted that J. regia survived and grew spontaneously in almost completely isolated stands in its Asian native range after the Last Glacial Maximum. Despite its natural geographic isolation, J. regia evolved over many centuries under the influence of human management and exploitation. We evaluated the hypothesis that the current distribution of natural genetic resources of common walnut in Asia is, at least in part, the product of ancient anthropogenic dispersal, human cultural interactions, and afforestation. Genetic analysis combined with ethno-linguistic and historical data indicated that ancient trade routes such as the Persian Royal Road and Silk Road enabled long-distance dispersal of J. regia from Iran and Trans-Caucasus to Central Asia, and from Western to Eastern China. Ancient commerce also disrupted the local spatial genetic structure of autochthonous walnut populations between Tashkent and Samarkand (Central-Eastern Uzbekistan), where the northern and central routes of the Northern Silk Road converged. A significant association between ancient language phyla and the genetic structure of walnut populations is reported even after adjustment for geographic distances that could have affected both walnut gene flow and human commerce over the centuries. Beyond the economic importance of common walnut, our study delineates an alternative approach for understanding how the genetic resources of long-lived perennial tree species may be affected by the interaction of geography and human history. PMID:26332919

  10. Ancient Humans Influenced the Current Spatial Genetic Structure of Common Walnut Populations in Asia

    PubMed Central

    Pollegioni, Paola; Woeste, Keith E.; Chiocchini, Francesca; Del Lungo, Stefano; Olimpieri, Irene; Tortolano, Virginia; Clark, Jo; Hemery, Gabriel E.; Mapelli, Sergio; Malvolti, Maria Emilia

    2015-01-01

    Common walnut (Juglans regia L) is an economically important species cultivated worldwide for its wood and nuts. It is generally accepted that J. regia survived and grew spontaneously in almost completely isolated stands in its Asian native range after the Last Glacial Maximum. Despite its natural geographic isolation, J. regia evolved over many centuries under the influence of human management and exploitation. We evaluated the hypothesis that the current distribution of natural genetic resources of common walnut in Asia is, at least in part, the product of ancient anthropogenic dispersal, human cultural interactions, and afforestation. Genetic analysis combined with ethno-linguistic and historical data indicated that ancient trade routes such as the Persian Royal Road and Silk Road enabled long-distance dispersal of J. regia from Iran and Trans-Caucasus to Central Asia, and from Western to Eastern China. Ancient commerce also disrupted the local spatial genetic structure of autochthonous walnut populations between Tashkent and Samarkand (Central-Eastern Uzbekistan), where the northern and central routes of the Northern Silk Road converged. A significant association between ancient language phyla and the genetic structure of walnut populations is reported even after adjustment for geographic distances that could have affected both walnut gene flow and human commerce over the centuries. Beyond the economic importance of common walnut, our study delineates an alternative approach for understanding how the genetic resources of long-lived perennial tree species may be affected by the interaction of geography and human history. PMID:26332919

  11. Anti-tumor angiogenesis effect of genetic fusion vaccine encoding murine beta-defensin 2 and tumor endothelial marker-8 in a CT-26 murine colorectal carcinoma model

    PubMed Central

    Liu, Ping; Xie, Ganfeng; Geng, Peiliang; Zheng, Chenhong; Li, Jianjun; Pan, Feng; Ruan, Zhihua; Liang, Houjie

    2015-01-01

    Tumor endothelial marker 8 (TEM8) is an endothelial-specific marker that is upregulated during tumor angiogenesis. We previously demonstrated that DNA-based vaccine encoding xenogeneic TEM8 can potentiate anti-angiogenesis immunotherapy of malignancy; nevertheless, it remains to be improved in minimizing immune tolerance. Recently, it has been reported that murine beta-defensin 2 (MBD2) is chemotactic for immature dendritic cells and plays a pivotal role in breaking immune tolerance. Herein, we constructed a genetic fusion vaccine encoding murine TEM8 and MBD2 to investigate whether the novel vaccine preferentially elicits therapeutic antitumor immune responses and suppresses cancerous angiogenesis in mouse models. The anti-angiogenesis effect was determined by microvessel density (MVD) using immunohistochemical staining. The efficacy of the fusion vaccine was primarily assessed by detecting cytotoxic T lymphocyte activity (51Cr-release assay). Enzyme-linked immunosorbent spot (ELISpot) assay was used to detect TEM8-specific INF-γ production, and the activity of CTL was further verified by a depletion of CD8+ T cells via anti-CD8 monoclonal antibody. Our results showed that the DNA fusion vaccine possessed an enhanced therapeutic antitumor immunity through anti-angiogenesis in BALB/c mice inoculated with CT26 cells, and this effect was generally attributed to stimulation of an antigen specific CD8+ T-cell response against mTEM8. In conclusion, our study demonstrated that the fusion vaccine based on mTEM8 and MBD2 induced autoimmunity against endothelial cells, resulting in deceleration of tumor growth, and could be potential therapeutical application in clinic. PMID:26064415

  12. Timing of HPV vaccine intervals among United States teens with consideration to the current ACIP schedule and the WHO 2-dose schedule.

    PubMed

    Cloessner, Emily A; Stokley, Shannon; Yankey, David; Markowitz, Lauri E

    2016-06-01

    The current recommendation for human papillomavirus (HPV) vaccination in the United States is for 3 doses to be administered over a 6 month period. In April 2014, the World Health Organization (WHO) recommended adoption of a 2-dose schedule, with doses spaced a minimum of 6 months apart, for teens who begin the series before age 15. We analyzed data from the 2013 National Immunization Survey-Teen to examine the timing of second and third dose receipt among US adolescents. All analyses were restricted to adolescents age 13-17 y who had adequate provider data. The Wilcoxon-Mann-Whitney test measured differences in time to receive vaccine doses among demographic and socioeconomic groups. Logistic regression identified socioeconomic characteristics associated with receiving the second dose of HPV vaccine at least 6 months after the first dose. The median time for teens to receive the second dose of HPV vaccine was 2.6 months after the first dose, and the median time to receive the third dose was 4.9 months after the second dose. Minority teens and teens living below the poverty level took significantly longer to receive doses. Among teens that initiated the HPV vaccine series before age 15 y, 28.6% received the second dose at least 6 months after the first dose. If these teens, who met the WHO criteria for up-to-date HPV vaccination, were classified as having completed the vaccination series, overall coverage in the US would increase 3.9 percentage points, with African American and Hispanic teens having the greatest increases in coverage. PMID:26587886

  13. Live porcine reproductive and respiratory syndrome virus vaccines: current status and future direction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980's. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the fi...

  14. Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection.

    PubMed

    Liu, Wei; Tan, Zhoulin; Xue, Jinfeng; Luo, Wenjin; Song, Hui; Lv, Xiaobo; Zheng, Tianjing; Xi, Tao; Xing, Yingying

    2016-07-01

    The gastric bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans and plays a critical role in the development of gastritis, peptic ulceration and gastric adenocarcinoma. Consequently, the eradication of H. pylori might contribute to the prevention of H. pylori-associated gastric diseases. In this study, a multi-epitope vaccine CTB-UE (CUE) was displayed on the surface of non-genetically modified Lactococcus lactis particles (GEM) to enhance immunogenicity. This particulate vaccine CUE-GEM induced serum and mucosal specific antibody responses against native H. pylori urease and provided potent protection to eliminate H. pylori colonization and relieve gastritis in an H. pylori-infected BALB/c mouse model. The immuno-protective mechanisms are highly associated with CD4(+) Th cell-mediated and humoral immunity, especially local immunity. There might be two main aspects of this association. One aspect is related to the suppression of urease activity by promotion of the production of specific mucosal neutralizing antibody. The other aspect is correlated with alleviating gastritis by regulating the gastric pro-inflammatory cytokine profile, especially IFN-γ and IL-17. These results demonstrated that conjugating antigen vaccines with GEM particles could lead to promising oral therapeutic vaccine formulations against H. pylori infection. PMID:26846746

  15. Optimization of influenza A vaccine virus by reverse genetic using chimeric HA and NA genes with an extended PR8 backbone.

    PubMed

    Medina, Julie; Boukhebza, Houda; De Saint Jean, Amélie; Sodoyer, Régis; Legastelois, Isabelle; Moste, Catherine

    2015-08-20

    The yield of influenza antigen production may significantly vary between vaccine strains; for example the A/California/07/09 (H1N1)-X179A vaccine virus, prepared during 2009 influenza pandemic, presented a low antigen yield in eggs compared to other seasonal H1N1 reassortants. In this study a bi-chimeric virus expressing HA and NA genes with A/Puerto Rico/8/34 (H1N1) (PR8) and X179A domains was rescued by reverse genetics using a mixture of Vero/CHOK1 cell lines (Medina et al. [7]). The bi-chimeric virus obtained demonstrated to yield much larger amounts of HA than X179A in eggs as measured by single-radial-immunodiffusion (SRID), the reference method to quantify HA protein in influenza vaccine. Such kind of optimized virus using PR8 backbone derived chimeric glycoproteins could be used as improved seed viruses for vaccine production. PMID:26206270

  16. Vaccine-Preventable Diseases of Childhood. January 1986 through August 1988. Current Bibliographies in Medicine No. 88-12.

    ERIC Educational Resources Information Center

    National Library of Medicine (DHHS/NIH), Bethesda, MD.

    Unless there are contraindications, there are seven diseases for which the Centers for Disease Control recommends all children be vaccinated: (1) diphtheria; (2) measles; (3) mumps; (4) pertussis; (5) poliomyelitis; (6) rubella; and (7) tetanus. The 748 references in this bibliography relate to various aspects of these vaccines and the diseases…

  17. Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Central and Eastern Europe.

    PubMed

    Poljak, Mario; Seme, Katja; Maver, Polona J; Kocjan, Boštjan J; Cuschieri, Kate S; Rogovskaya, Svetlana I; Arbyn, Marc; Syrjänen, Stina

    2013-12-31

    We present a review of current cervical cancer screening practices, the implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 Central and Eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and the Former Yugoslav Republic (FYR) of Macedonia. Since published data were relatively scarce, two detailed surveys were conducted during August-October 2011 and in January 2013 to obtain relevant and updated information. The mean prevalence of HPV infection in 8610 women with normal cervical cytology from the region was 12.6%, with HPV16 being the most frequent HPV type. The overall HPV DNA prevalence in women with high-grade cervical lesions was 78.1%. HPV DNA was found in 86.6% of cervical cancers; the combined prevalence of HPV16/18 among HPV positive cases was 87.5%. The overall HPV DNA prevalence in genital warts and laryngeal papillomas was 94.8% and 95.2%, respectively, with HPV6 and HPV11 being the most frequent types. Opportunistic and organized cervical screening, mainly based on conventional cytology, is performed in nine and seven countries in the region, respectively, with the proposed age of the start of screening ranging from 20 to 30 years and the estimated coverage ranging from a few percent to over 70%. At least one of the current HPV prophylactic vaccines is registered in all Central and Eastern European countries except Montenegro. Only Bulgaria, Czech Republic, FYR Macedonia, Latvia, Romania and Slovenia have actually integrated HPV vaccination into their national immunization programme and currently provide routine vaccination free of charge to the primary target population. The key reasons for lack of implementation of HPV vaccination into the national immunization programme are high vaccine cost and

  18. Correlates of protective immunity following whole sporozoite vaccination against malaria.

    PubMed

    Doll, Katherine L; Harty, John T

    2014-08-01

    Human infection with Plasmodium parasites remains a serious global health crisis, leading to more than 600,000 deaths annually. Currently, no licensed vaccine is available to alleviate this malaria disease burden and vaccination with the most advanced antimalarial vaccine candidate, RTS,S, provides limited protection that wanes over time. To date, the only vaccination strategy capable of inducing complete, long-lasting protection in human subjects is administration of attenuated whole sporozoites. Several approaches for vaccination with attenuated whole sporozoites have been clinically tested in humans and include vaccination with radiation or genetically attenuated sporozoites or with virulent sporozoites concurrent with administration of antimalarial drug cover. Rodent studies with these three attenuated whole sporozoite vaccination (WSV) approaches provide insights into the immune correlates of vaccine-induced protection. The majority of these studies have identified a critical role for liver-stage parasite-directed CD8 T cells in providing protection with possible contributions from Plasmodium-specific CD4 T cells or antibodies. Together, rodent and human vaccination studies with attenuated WSV may lead to an understanding of the correlates of protective immunity against malarial disease, and the development of new, highly efficacious vaccines. PMID:24825778

  19. Reverse genetics vaccine seeds for influenza: Proof of concept in the source of PB1 as a determinant factor in virus growth and antigen yield.

    PubMed

    Gíria, Marta; Santos, Luís; Louro, João; Rebelo de Andrade, Helena

    2016-09-01

    Growth deficits of reverse genetics vaccine seeds have compromised effective immunization. The impairment has been attributed to sub-optimal protein interactions. Some level of dependence may exist between PB1 and antigenic glycoproteins, however, further research is necessary to clarify the extent to which it can be used in favor of seed production. Our objective was to establish proof of concept on the phenotypic outcome of PB1 source in the PR8: A(H1N1)pdm09 reassortants. Reassortants were generated with the gene constellation of the classical 6:2 PR8: HA, NApdm09 seed prototype and the 5:3 reassortant PR8: HA, NA, PB1pdm09. Viral growth and antigen yield were evaluated 12-60h post-infection. The 5:3 reassortant presented statistically significant growth and antigen yield improvements when compared to the 6:2. We believe these findings to be of promising value to vaccine research towards an improvement of reverse genetic seeds, an overall more cost-effective vaccine manufacture and timely delivery. PMID:27240145

  20. The Genetics of Non-conventional Wine Yeasts: Current Knowledge and Future Challenges

    PubMed Central

    Masneuf-Pomarede, Isabelle; Bely, Marina; Marullo, Philippe; Albertin, Warren

    2016-01-01

    Saccharomyces cerevisiae is by far the most widely used yeast in oenology. However, during the last decade, several other yeasts species has been purposed for winemaking as they could positively impact wine quality. Some of these non-conventional yeasts (Torulaspora delbrueckii, Metschnikowia pulcherrima, Pichia kluyveri, Lachancea thermotolerans, etc.) are now proposed as starters culture for winemakers in mixed fermentation with S. cerevisiae, and several others are the subject of various studies (Hanseniaspora uvarum, Starmerella bacillaris, etc.). Along with their biotechnological use, the knowledge of these non-conventional yeasts greatly increased these last 10 years. The aim of this review is to describe the last updates and the current state-of-art of the genetics of non-conventional yeasts (including S. uvarum, T. delbrueckii, S. bacillaris, etc.). We describe how genomics and genetics tools provide new data into the population structure and biodiversity of non-conventional yeasts in winemaking environments. Future challenges will lie on the development of selection programs and/or genetic improvement of these non-conventional species. We discuss how genetics, genomics and the advances in next-generation sequencing will help the wine industry to develop the biotechnological use of non-conventional yeasts to improve the quality and differentiation of wines. PMID:26793188

  1. Efficacy of a recombinant HVT-H5 vaccine against challenge with two genetically divergent Indonesian HPAI H5N1 strains.

    PubMed

    Soejoedono, Retno D; Murtini, Sri; Palya, Vilmos; Felföldi, Balázs; Mató, Tamás; Gardin, Yannick

    2012-12-01

    The swift evolution rate of avian influenza (AI) H5N1 virus demands constant efforts to update inactivated vaccines to match antigenically with the emerging new field virus strains. Recently, a recombinant turkey herpesvirus (rHVT)-AI vaccine, rHVT-H5, expressing the HA gene of a highly pathogenic avian influenza (HPAI) H5N1 clade 2.2 A/Swan/Hungary/499/ 2006 strain inserted into FC-126 strain of HVT vector, has been developed to combat current threats in poultry industry. Here, we present the results of two trials where rHVT-H5 was tested alone or in combination with inactivated H5N1 vaccines (the latter vaccines contained antigens produced by using a clade 2.1.3 HPAI H5N1 virus [A/Ck/WestJava-Nagrak/2007] in the first trial or mixture of antigen produced by strain A/Ck/WestJava-Nagrak/2007 and A/Ck/Banten-Tangerang/2010 [bivalent vaccine] for second trial) in broiler chickens (Gallus gallus domesticus) carrying maternally derived antibodies to H5N1 and then challenged with Indonesian HPAI H5N1 field isolates. The effectiveness of vaccination was evaluated on the basis of clinical protection (morbidity and mortality) and measurement of virus shedding after challenge. Immune response to vaccination was followed by serology. In the first experiment, chickens were vaccinated at the day of hatch with rHVT-H5 alone (Group 1) or combined with inactivated vaccine at day old (Group 2) or at 10 days of age (Group 3). The chickens along with nonvaccinated hatch-mates were challenged at 28 days of age with the HPAI H5N1 field isolate dade 2.1.3 A/Chicken/WestJava-Subang/29/2007. Eighty, 100%, and 80% clinical protection was recorded in Group 1, 2, and 3, respectively. A similar experiment was performed a second time, but the chicks in Group 3 received the inactivated vaccine earlier, at 7 days of age. Challenge was performed at 28 days of age using a different H5N1 isolate, clade 2.1.3 A/Ck/Purwakarta-Cilingga/142/10. Clinical protection achieved in the second trial was 95

  2. Vaccinations for the Older Adult.

    PubMed

    Gnanasekaran, Gowrishankar; Biedenbender, Rex; Davidson, Harley Edward; Gravenstein, Stefan

    2016-08-01

    Vaccine response declines with age, but currently recommended vaccines are safe and effective in reducing, if not preventing, disease altogether. Over the last decade, advancements in vaccine immunogenicity, either by increasing dose or conjugating vaccines to protein, have resulted in more immunogenic vaccines that also seem more effective in reducing clinical disease both for influenza and pneumococcus. Meanwhile, there is a resurgence in incident pertussis, exceeding prevalence from five decades ago, adding older adults to a recommended target vaccination group. This article discusses currently available vaccines, in the context of current epidemiology and recommendations, for older adults. PMID:27394026

  3. [Developments in HPV vaccination].

    PubMed

    de Melker, Hester; Kenter, Gemma; van Rossum, Tekla; Conyn-van Spaendonck, Marina

    2012-01-01

    Vaccination against the human papilloma virus (HPV) has been included in the national Vaccination Programme of the Netherlands for 12-year-old girls since 2010. Vaccination coverage for the birth cohort of 1997 was 56.; there is a gradual increase in uptake. Continuous safety monitoring brought no new unknown serious side effects to light; many girls suffered from transient symptoms such as painful arm, fatigue and headache. After the current vaccines that protect against HPV types 2 and 4 types, respectively and induce some cross protection, vaccines are being developed that can induce broader protection. HPV vaccination of 12-year-old girls is cost-effective, even for relatively low vaccination coverage. The potential protection of HPV vaccination extends beyond prevention of cervical cancer by preventing other oncological manifestations of HPV infection in women as well as men and genital warts. The preventive HPV vaccines do not appear to be effective in treating existing abnormalities. PMID:23171565

  4. Porcine reproductive and respiratory syndrome virus vaccines: Immunogenicity, efficacy and safety aspects

    PubMed Central

    Charerntantanakul, Wasin

    2012-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) infection is the leading cause of economic casualty in swine industry worldwide. The virus can cause reproductive failure, respiratory disease, and growth retardation in the pigs. This review deals with current status of commercial PRRS vaccines presently used to control PRRS. The review focuses on the immunogenicity, protective efficacy and safety aspects of the vaccines. Commercial PRRS modified-live virus (MLV) vaccine elicits delayed humoral and cell-mediated immune responses following vaccination. The vaccine confers late but effective protection against genetically homologous PRRSV, and partial protection against genetically heterologous virus. The MLV vaccine is of concern for its safety as the vaccine virus can revert to virulence and cause diseases. PRRS killed virus (KV) vaccine, on the other hand, is safe but confers limited protection against either homologous or heterologous virus. The KV vaccine yet helps reduce disease severity when administered to the PRRSV-infected pigs. Although efforts have been made to improve the immunogenicity, efficacy and safety of PRRS vaccines, a better vaccine is still needed in order to protect against PRRSV. PMID:24175208

  5. The Current and Future Use of Ridge Regression for Prediction in Quantitative Genetics

    PubMed Central

    de Vlaming, Ronald; Groenen, Patrick J. F.

    2015-01-01

    In recent years, there has been a considerable amount of research on the use of regularization methods for inference and prediction in quantitative genetics. Such research mostly focuses on selection of markers and shrinkage of their effects. In this review paper, the use of ridge regression for prediction in quantitative genetics using single-nucleotide polymorphism data is discussed. In particular, we consider (i) the theoretical foundations of ridge regression, (ii) its link to commonly used methods in animal breeding, (iii) the computational feasibility, and (iv) the scope for constructing prediction models with nonlinear effects (e.g., dominance and epistasis). Based on a simulation study we gauge the current and future potential of ridge regression for prediction of human traits using genome-wide SNP data. We conclude that, for outcomes with a relatively simple genetic architecture, given current sample sizes in most cohorts (i.e., N < 10,000) the predictive accuracy of ridge regression is slightly higher than the classical genome-wide association study approach of repeated simple regression (i.e., one regression per SNP). However, both capture only a small proportion of the heritability. Nevertheless, we find evidence that for large-scale initiatives, such as biobanks, sample sizes can be achieved where ridge regression compared to the classical approach improves predictive accuracy substantially. PMID:26273586

  6. Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

    PubMed Central

    DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

  7. Genetic considerations for mollusk production in aquaculture: current state of knowledge

    PubMed Central

    Astorga, Marcela P.

    2014-01-01

    In 2012, world mollusk production in aquaculture reached a volume of 15,171,000 tons, representing 23% of total aquaculture production and positioning mollusks as the second most important category of aquaculture products (fishes are the first). Clams and oysters are the mollusk species with the highest production levels, followed in descending order by mussels, scallops, and abalones. In view of the increasing importance attached to genetic information on aquaculture, which can help with good maintenance and thus the sustainability of production, the present work offers a review of the state of knowledge on genetic and genomic information about mollusks produced in aquaculture. The analysis was applied to mollusks which are of importance for aquaculture, with emphasis on the 5 species with the highest production levels. According to FAO, these are: Japanese clam Ruditapes philippinarum; Pacific oyster Crassostrea gigas; Chilean mussel Mytilus chilensis; Blood clam Anadara granosa and Chinese clam Sinonovacula constricta. To date, the genomes of 5 species of mollusks have been sequenced, only one of which, Crassostrea gigas, coincides with the species with the greatest production in aquaculture. Another important species whose genome has been sequenced is Mytilus galloprovincialis, which is the second most important mussel in aquaculture production, after M. chilensis. Few genetic improvement programs have been reported in comparison with the number reported in fish species. The most commonly investigated species are oysters, with at least 5 genetic improvement programs reported, followed by abalones with 2 programs and mussels with one. The results of this work will establish the current situation with respect to the genetics of mollusks which are of importance for aquaculture production, in order to assist future decisions to ensure the sustainability of these resources. PMID:25540651

  8. Current Landscape and New Paradigms of Proficiency Testing and External Quality Assessment for Molecular Genetics

    PubMed Central

    Kalman, Lisa V.; Lubin, Ira M.; Barker, Shannon; du Sart, Desiree; Elles, Rob; Grody, Wayne W.; Pazzagli, Mario; Richards, Sue; Schrijver, Iris; Zehnbauer, Barbara

    2015-01-01

    Context Participation in proficiency testing (PT) or external quality assessment (EQA) programs allows the assessment and comparison of test performance among different clinical laboratories and technologies. In addition to the approximately 2300 tests for individual genetic disorders, recent advances in technology have enabled the development of clinical tests which quickly and economically analyze the entire human genome. New PT/EQA approaches are needed to ensure the continued quality of these complex tests. Objective To review the availability and scope of PT/EQA for molecular genetic testing for inherited conditions in Europe, Australasia and the United States; to evaluate the successes and demonstrated value of available PT/EQA programs; and to examine the challenges to the provision of comprehensive PT/EQA posed by new laboratory practices and methodologies. Data Sources The available literature on this topic was reviewed and supplemented with personal experiences of several PT/EQA providers. Conclusions PT/EQA schemes are available for common genetic disorders tested in many clinical laboratories, but are not available for most genetic tests offered by only one or a few laboratories. Provision of broad, method-based PT schemes, such as DNA sequencing, would allow assessment of a large number of tests for which formal PT is not currently available. Participation in PT/EQA improves the quality of testing by identifying inaccuracies that laboratories can trace to errors in the testing process. Areas of research and development to ensure that PT/EQA programs can meet the needs of new and evolving genetic tests and technologies are identified and discussed. PMID:23808472

  9. Recombinant influenza vaccines.

    PubMed

    Sedova, E S; Shcherbinin, D N; Migunov, A I; Smirnov, Iu A; Logunov, D Iu; Shmarov, M M; Tsybalova, L M; Naroditskiĭ, B S; Kiselev, O I; Gintsburg, A L

    2012-10-01

    This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery platform for a variety of genetic vaccines. Adenoviruses can efficiently penetrate the human organism through mucosal epithelium, thus providing long-term antigen persistence and induction of the innate immune response. This review provides an overview of the practicability of the production of new recombinant influenza cross-protective vaccines on the basis of adenoviral vectors expressing hemagglutinin genes of different influenza strains. PMID:23346377

  10. Typhoid fever vaccination strategies.

    PubMed

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. PMID:25902360

  11. Live Vaccination Tactics: Possible Approaches for Controlling Visceral Leishmaniasis

    PubMed Central

    Saljoughian, Noushin; Taheri, Tahareh; Rafati, Sima

    2014-01-01

    Vaccination with durable immunity is the main goal and fundamental to control leishmaniasis. To stimulate the immune response, small numbers of parasites are necessary to be presented in the mammalian host. Similar to natural course of infection, strategy using live vaccine is more attractive when compared to other approaches. Live vaccines present the whole spectrum of antigens to the host immune system in the absence of any adjuvant. Leishmanization was the first effort for live vaccination and currently used in a few countries against cutaneous leishmaniasis, in spite of their obstacle and safety. Then, live attenuated vaccines developed with similar promotion of creating long-term immunity in the host with lower side effect. Different examples of attenuated strains are generated through long-term in vitro culturing, culturing under drug pressure, temperature sensitivity, and chemical mutagenesis, but none is safe enough and their revision to virulent form is possible. Attenuation through genetic manipulation and disruption of virulence factors or essential enzymes for intracellular survival are among other approaches that are intensively under study. Other designs to develop live vaccines for visceral form of leishmaniasis are utilization of live avirulent microorganisms such as Lactococcus lactis, Salmonella enterica, and Leishmania tarentolae called as vectored vaccine. Apparently, these vaccines are intrinsically safer and can harbor the candidate antigens in their genome through different genetic manipulation and create more potential to control Leishmania parasite as an intracellular pathogen. PMID:24744757

  12. Willingness of European healthcare workers to undergo vaccination against seasonal influenza: current situation and suggestions for improvement.

    PubMed

    Kassianos, George

    2015-01-01

    Uptake of vaccination against seasonal influenza in healthcare workers (HCWs) is, in general, low (vaccine coverage of 6-54%), as is awareness of its importance, and has been decreasing in most European Union (EU) countries in recent years. By virtue of their working environment, HCWs are at an increased risk of influenza infection and of subsequently transmitting the virus to vulnerable patients, in whom disease burden is significant. It could be argued that a similar or higher target vaccination rate to that recommended for older age groups and people with chronic medical conditions (75%) should be applied to HCWs, and the European Council recommends Member States to improve vaccination coverage in this population. In this context, better education of HCWs is needed to increase awareness and highlight the importance of HCW vaccination for the benefit of public health, particularly for their patients, who may be at risk of serious complications that could lead to disability or death. Secondary to these professional responsibilities, personal benefits (as well as benefits to close family and friends) should also be emphasised. Misconceptions that create barriers to vaccination need to be discussed openly and objections placed in the context of public health. PMID:25657810

  13. Willingness of European healthcare workers to undergo vaccination against seasonal influenza: current situation and suggestions for improvement

    PubMed Central

    Kassianos, George

    2015-01-01

    Uptake of vaccination against seasonal influenza in healthcare workers (HCWs) is, in general, low (vaccine coverage of 6–54%), as is awareness of its importance, and has been decreasing in most European Union (EU) countries in recent years. By virtue of their working environment, HCWs are at an increased risk of influenza infection and of subsequently transmitting the virus to vulnerable patients, in whom disease burden is significant. It could be argued that a similar or higher target vaccination rate to that recommended for older age groups and people with chronic medical conditions (75%) should be applied to HCWs, and the European Council recommends Member States to improve vaccination coverage in this population. In this context, better education of HCWs is needed to increase awareness and highlight the importance of HCW vaccination for the benefit of public health, particularly for their patients, who may be at risk of serious complications that could lead to disability or death. Secondary to these professional responsibilities, personal benefits (as well as benefits to close family and friends) should also be emphasised. Misconceptions that create barriers to vaccination need to be discussed openly and objections placed in the context of public health. PMID:25657810

  14. Molecular Markers and Cotton Genetic Improvement: Current Status and Future Prospects

    PubMed Central

    Malik, Waqas; Iqbal, Muhammad Zaffar; Ali Khan, Asif; Qayyum, Abdul; Ali Abid, Muhammad; Noor, Etrat; Qadir Ahmad, Muhammad; Hasan Abbasi, Ghulam

    2014-01-01

    Narrow genetic base and complex allotetraploid genome of cotton (Gossypium hirsutum L.) is stimulating efforts to avail required polymorphism for marker based breeding. The availability of draft genome sequence of G. raimondii and G. arboreum and next generation sequencing (NGS) technologies facilitated the development of high-throughput marker technologies in cotton. The concepts of genetic diversity, QTL mapping, and marker assisted selection (MAS) are evolving into more efficient concepts of linkage disequilibrium, association mapping, and genomic selection, respectively. The objective of the current review is to analyze the pace of evolution in the molecular marker technologies in cotton during the last ten years into the following four areas: (i) comparative analysis of low- and high-throughput marker technologies available in cotton, (ii) genetic diversity in the available wild and improved gene pools of cotton, (iii) identification of the genomic regions within cotton genome underlying economic traits, and (iv) marker based selection methodologies. Moreover, the applications of marker technologies to enhance the breeding efficiency in cotton are also summarized. Aforementioned genomic technologies and the integration of several other omics resources are expected to enhance the cotton productivity and meet the global fiber quantity and quality demands. PMID:25401149

  15. Molecular markers and cotton genetic improvement: current status and future prospects.

    PubMed

    Malik, Waqas; Ashraf, Javaria; Iqbal, Muhammad Zaffar; Khan, Asif Ali; Qayyum, Abdul; Ali Abid, Muhammad; Noor, Etrat; Ahmad, Muhammad Qadir; Abbasi, Ghulam Hasan

    2014-01-01

    Narrow genetic base and complex allotetraploid genome of cotton (Gossypium hirsutum L.) is stimulating efforts to avail required polymorphism for marker based breeding. The availability of draft genome sequence of G. raimondii and G. arboreum and next generation sequencing (NGS) technologies facilitated the development of high-throughput marker technologies in cotton. The concepts of genetic diversity, QTL mapping, and marker assisted selection (MAS) are evolving into more efficient concepts of linkage disequilibrium, association mapping, and genomic selection, respectively. The objective of the current review is to analyze the pace of evolution in the molecular marker technologies in cotton during the last ten years into the following four areas: (i) comparative analysis of low- and high-throughput marker technologies available in cotton, (ii) genetic diversity in the available wild and improved gene pools of cotton, (iii) identification of the genomic regions within cotton genome underlying economic traits, and (iv) marker based selection methodologies. Moreover, the applications of marker technologies to enhance the breeding efficiency in cotton are also summarized. Aforementioned genomic technologies and the integration of several other omics resources are expected to enhance the cotton productivity and meet the global fiber quantity and quality demands. PMID:25401149

  16. A brief history of autism, the autism/vaccine hypothesis and a review of the genetic basis of autism spectrum disorders.

    PubMed

    Blake, Jerome; Hoyme, H Eugene; Crotwell, Patricia L

    2013-01-01

    Autism spectrum disorders (ASD) represent a common spectrum of developmental disabilities, sharing deficits in social interactions, communication and restricted interests or repetitive behaviors with difficult transitions. In this article, we review the history of the identification and classification of autism and the origin of the now widely-debunked autism/vaccine hypothesis. The differences between syndromal (complex) and non-syndromal (essential) autism are described and illustrated with case descriptions where appropriate. Finally, the evidence that autism is fundamentally a genetic disease is discussed, including family studies, the role of DNA copy number variation and known single gene mutations. PMID:23444593

  17. Chimeric Pestivirus Experimental Vaccines.

    PubMed

    Reimann, Ilona; Blome, Sandra; Beer, Martin

    2016-01-01

    Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics. PMID:26458840

  18. Cochlear-Meningitis Vaccination

    MedlinePlus

    ... and otolaryngologists) and families should review the vaccination records of current and prospective cochlear implant recipients to ensure that all ... of Use Join Donate ENTConnect Contact Us ...

  19. Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease.

    PubMed

    McKibbin, Martin; Ahmed, Mushtaq; Allsop, Matthew J; Downey, Louise; Gale, Richard; Grant, Hilary Louise; Potrata, Barbara; Willis, Thomas A; Hewison, Jenny

    2014-09-01

    Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations. PMID:24398793

  20. Vaccines today, vaccines tomorrow: a perspective.

    PubMed

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  1. Vaccines today, vaccines tomorrow: a perspective

    PubMed Central

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  2. Phylogenetic analysis of human influenza A/H3N2 viruses isolated in 2015 in Germany indicates significant genetic divergence from vaccine strains.

    PubMed

    Mostafa, Ahmed; Abdelwhab, El-Sayed M; Slanina, Heiko; Hussein, Mohamed A; Kuznetsova, Irina; Schüttler, Christian G; Ziebuhr, John; Pleschka, Stephan

    2016-06-01

    Infections by H3N2-type influenza A viruses (IAV) resulted in significant numbers of hospitalization in several countries in 2014-2015, causing disease also in vaccinated individuals and, in some cases, fatal outcomes. In this study, sequence analysis of H3N2 viruses isolated in Germany from 1998 to 2015, including eleven H3N2 isolates collected early in 2015, was performed. Compared to the vaccine strain A/Texas/50/2012 (H3N2), the 2015 strains from Germany showed up to 4.5 % sequence diversity in their HA1 protein, indicating substantial genetic drift. The data further suggest that two distinct phylogroups, 3C.2 and 3C.3, with 1.6-2.3 % and 0.3-2.4 % HA1 nucleotide and amino acid sequence diversity, respectively, co-circulated in Germany in the 2014/2015 season. Distinct glycosylation patterns and amino acid substitutions in the hemagglutinin and neuraminidase proteins were identified, possibly contributing to the unusually high number of H3N2 infections in this season and providing important information for developing vaccines that are effective against both genotypes. PMID:26973232

  3. Probing Genetic Control of Swine Responses to PRRSV Infection: Current Progress of the PRRS Host Genetics Consortium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Understanding the role of host genetics in resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection, and the effects of PRRS on pig health and related growth, are goals of the PRRS Host Genetics Consortium (PHGC). Methods: The project uses a nursery pig model ...

  4. Probing genetic control of swine responses to PRRSV infection: Current Progress of the PRRS Host Genetics Consortium.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the role of host genetics in resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection, and the effects of PRRS on pig health and related growth, are goals of the PRRS Host Genetics Consortium (PHGC). The project uses a nursery pig model to assess pig resistan...

  5. Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

    PubMed

    Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

    2016-09-01

    Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. PMID:27523740

  6. Using genetic algorithms to optimise current and future health planning - the example of ambulance locations

    PubMed Central

    2010-01-01

    Background Ambulance response time is a crucial factor in patient survival. The number of emergency cases (EMS cases) requiring an ambulance is increasing due to changes in population demographics. This is decreasing ambulance response times to the emergency scene. This paper predicts EMS cases for 5-year intervals from 2020, to 2050 by correlating current EMS cases with demographic factors at the level of the census area and predicted population changes. It then applies a modified grouping genetic algorithm to compare current and future optimal locations and numbers of ambulances. Sets of potential locations were evaluated in terms of the (current and predicted) EMS case distances to those locations. Results Future EMS demands were predicted to increase by 2030 using the model (R2 = 0.71). The optimal locations of ambulances based on future EMS cases were compared with current locations and with optimal locations modelled on current EMS case data. Optimising the location of ambulance stations locations reduced the average response times by 57 seconds. Current and predicted future EMS demand at modelled locations were calculated and compared. Conclusions The reallocation of ambulances to optimal locations improved response times and could contribute to higher survival rates from life-threatening medical events. Modelling EMS case 'demand' over census areas allows the data to be correlated to population characteristics and optimal 'supply' locations to be identified. Comparing current and future optimal scenarios allows more nuanced planning decisions to be made. This is a generic methodology that could be used to provide evidence in support of public health planning and decision making. PMID:20109172

  7. Effectiveness of the E2-classical swine fever virus recombinant vaccine produced and formulated within whey from genetically transformed goats.

    PubMed

    Sánchez, O; Barrera, M; Farnós, O; Parra, N C; Salgado, E R; Saavedra, P A; Meza, C D; Rivas, C I; Cortez-San Martín, M; Toledo, J R

    2014-12-01

    Subunit recombinant vaccines against classical swine fever virus (CSFV) are a promising alternative to overcome practical and biosafety issues with inactivated vaccines. One of the strategies in evaluation under field conditions is the use of a new marker E2-based vaccine produced in the milk of adenovirally transduced goats. Previously we had demonstrated the efficacy of this antigen, which conferred early protection and long-lasting immunity in swine against CSFV infection. Here, we have used a simpler downstream process to obtain and formulate the recombinant E2 glycoprotein expressed in the mammary gland. The expression levels reached approximately 1.7 mg/ml, and instead of chromatographic separation of the antigen, we utilized a clarification process that eliminates the fat content, retains a minor amount of caseins, and includes an adenoviral inactivation step that improves the biosafety of the final formulation. In a vaccination and challenge experiment in swine, different doses of the E2 antigen contained within the clarified whey generated an effective immune response of neutralizing antibodies that protected all of the animals against a lethal challenge with CSFV. During the immunization and after challenge, the swine were monitored for adverse reactions related to the vaccine or symptoms of CSF, respectively. No adverse reactions or clinical signs of disease were observed in vaccinated animals, in which no replication of CSFV could be detected after challenge. Overall, we consider that the simplicity of the procedures proposed here is a further step toward the introduction and implementation of a commercial subunit vaccine against CSF. PMID:25274802

  8. Effectiveness of the E2-Classical Swine Fever Virus Recombinant Vaccine Produced and Formulated within Whey from Genetically Transformed Goats

    PubMed Central

    Sánchez, O.; Barrera, M.; Farnós, O.; Parra, N. C.; Salgado, E. R.; Saavedra, P. A.; Meza, C. D.; Rivas, C. I.; Cortez-San Martín, M.

    2014-01-01

    Subunit recombinant vaccines against classical swine fever virus (CSFV) are a promising alternative to overcome practical and biosafety issues with inactivated vaccines. One of the strategies in evaluation under field conditions is the use of a new marker E2-based vaccine produced in the milk of adenovirally transduced goats. Previously we had demonstrated the efficacy of this antigen, which conferred early protection and long-lasting immunity in swine against CSFV infection. Here, we have used a simpler downstream process to obtain and formulate the recombinant E2 glycoprotein expressed in the mammary gland. The expression levels reached approximately 1.7 mg/ml, and instead of chromatographic separation of the antigen, we utilized a clarification process that eliminates the fat content, retains a minor amount of caseins, and includes an adenoviral inactivation step that improves the biosafety of the final formulation. In a vaccination and challenge experiment in swine, different doses of the E2 antigen contained within the clarified whey generated an effective immune response of neutralizing antibodies that protected all of the animals against a lethal challenge with CSFV. During the immunization and after challenge, the swine were monitored for adverse reactions related to the vaccine or symptoms of CSF, respectively. No adverse reactions or clinical signs of disease were observed in vaccinated animals, in which no replication of CSFV could be detected after challenge. Overall, we consider that the simplicity of the procedures proposed here is a further step toward the introduction and implementation of a commercial subunit vaccine against CSF. PMID:25274802

  9. Protective immunity against alpha-cobratoxin following a single administration of a genetic vaccine encoding a non-toxic cobratoxin variant.

    PubMed

    Pergolizzi, Robert G; Dragos, Rachel; Ropper, Alexander E; Menez, André; Crystal, Ronald G

    2005-03-01

    Venomous snakebites result in almost 125,000 deaths per year worldwide. We present a new paradigm for the development of vaccines to protect against snakebite, using knowledge of the structure and action of specific toxins combined with a gene-based strategy to deliver a toxin gene modified to render it non-toxic while maintaining its three-dimensional structure and hence its ability to function as an immunogen. As a model for this approach, we developed a genetic vaccine to protect against alpha-cobratoxin (CTX), a potent, post-synaptic neurotoxin that is the major toxic component of the venom of Naja kaouthia, the monocellate cobra. To develop the vaccine, substitutions in the CTX cDNA were introduced at two residues critical for binding to the nicotinic acetylcholine receptor (Asp27 to Arg, Arg33 to Gly). The mutated CTX expression cassette was delivered in the context of a replication deficient adenovirus vector (AdmCTX). To assess whether expression of the mutated CTX in vivo leads to the development of protective immunity, BALB/c mice were challenged by IV administration of 2 microg of alpha-cobratoxin protein 21 or 63 days after administration of AdmCTX or Ad- Null (as a control; both, 10(9) particle units). Animals receiving AdmCTX but no alpha-cobratoxin challenge suffered no ill effects, but > or =80% of naive animals or those receiving the AdNull control vector died within 10 min from the alpha-cobratoxin challenge. In contrast, 100% of animals receiving a single dose of AdmCTX 21 or 63 days prior to alpha-cobratoxin challenge survived. The data demonstrates that an adenovirus-based vaccine can be developed to protect against lethal challenge with a potent snake venom. The effectiveness of this approach might serve as a basis to consider the development of a global public health program to protect those at risk for death by snakebite. PMID:15812224

  10. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine

    PubMed Central

    Nieto-Torres, Jose L.; DeDiego, Marta L.; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-01-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV. PMID:26513244

  11. Vaccines: the Fourth Century▿

    PubMed Central

    Plotkin, Stanley A.

    2009-01-01

    Vaccine development, which began with Edward Jenner's observations in the late 18th century, has entered its 4th century. From its beginnings, with the use of whole organisms that had been weakened or inactivated, to the modern-day use of genetic engineering, it has taken advantage of the tools discovered in other branches of microbiology. Numerous successful vaccines are in use, but the list of diseases for which vaccines do not exist is long. However, the multiplicity of strategies now available, discussed in this article, portends even more successful development of vaccines. PMID:19793898

  12. Novel Vaccination Strategies against Tuberculosis

    PubMed Central

    Andersen, Peter; Kaufmann, Stefan H.E.

    2014-01-01

    The tuberculosis (TB) pandemic continues to rampage despite widespread use of the BCG (Bacillus Calmette–Guérin) vaccine. Novel vaccination strategies are urgently needed to arrest global transmission and prevent the uncontrolled development of multidrug-resistant forms of Mycobacterium tuberculosis. Over the last two decades, considerable progress has been made in the field of vaccine development with numerous innovative preclinical candidates and more than a dozen vaccines in clinical trials. These vaccines are developed either as boosters of the current BCG vaccine or as novel prime vaccines to replace BCG. Given the enormous prevalence of latent TB infection, vaccines that are protective on top of an already established infection remain a high priority and a significant scientific challenge. Here we discuss the current state of TB vaccine research and development, our understanding of the underlying immunology, and the requirements for an efficient TB vaccine. PMID:24890836

  13. Genetics

    MedlinePlus

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  14. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  15. Genetic stability of a recombinant adenovirus vaccine vector seed library expressing human papillomavirus type 16 E6 and E7 proteins

    PubMed Central

    WU, JIE; CHEN, KE-DA; GAO, MENG; CHEN, GANG; JIN, SU-FENG; ZHUANG, FANG-CHENG; WU, XIAO-HONG; JIANG, YUN-SHUI; LI, JIAN-BO

    2015-01-01

    The aim of the present study was to understand the genetic stability of a master seed bank (MSB) and a working seed bank (WSB) of an adenovirus vector vaccine expressing the human papillomavirus (HPV) type 16 E6 and E7 fusion proteins (Ad-HPV16E6E7). Microscopic examination and viral infectious efficacy were used to measure the infectious titers of the Ad-HPV16E6E7 MSB and WSB. Polymerase chain reaction was used to analyze the stability of the Ad-HPV16E6E7 target gene insertion, while western blot analysis and immunofluorescence were used to assess the expression levels of the Ad-HPV16E6E7 target protein. A C57BL/6 mouse TC-1 tumor cell growth inhibition model was used to evaluate the biological effect of Ad-HPV16E6E7 administration. The infectious titers of the Ad-HPV16E6E7 MSB and WSB were 6.31×109 IU/ml and 3.0×109 IU/ml, respectively. In addition, the expression levels of the inserted target genes and target proteins were found to be stable. In the mouse TC-1 tumor inhibition analysis, when the virus titers of the Ad-HPV16E6E7 MSB and WSB were 109 IU/ml, the tumor inhibition rate was 100%, which was significantly different when compared with the control group (χ2MSB=20.00 and χ2WSB=20.00; P<0.01). Therefore, the Ad-HPV16E6E7 vaccine seed bank is genetically stable and meets the requirements for vaccine development. PMID:25780403

  16. Shingles Vaccination: What You Need to Know

    MedlinePlus

    ... vaccine. Contact your insurer to find out. Private health insurance Most private health insurance plans cover the vaccine for people 60 years ... shingles vaccine). If you do not currently have health insurance, learn more about affordable health coverage options . To ...

  17. Genetics of Attention Deficit Hyperactivity Disorder: A Current Review and Future Prospects

    ERIC Educational Resources Information Center

    Levy, Florence; Hay, David A.; Bennett, Kellie S.

    2006-01-01

    While there have been significant advances in both the behaviour genetics and molecular genetics of Attention Deficit Hyperactivity Disorder (ADHD), researchers are now beginning to develop hypotheses about relationships between phenotypes and genetic mechanisms. Twin studies are able to model genetic, shared environmental and non-shared…

  18. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    PubMed Central

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  19. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement.

    PubMed

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  20. New tuberculosis vaccines.

    PubMed

    Martín Montañés, Carlos; Gicquel, Brigitte

    2011-03-01

    The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable. For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases. Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines. After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices. PMID:21420568

  1. Genetic and Antigenic Typing of Seasonal Influenza Virus Breakthrough Cases from a 2008-2009 Vaccine Efficacy Trial

    PubMed Central

    Durviaux, Serge; Treanor, John; Beran, Jiri; Duval, Xavier; Esen, Meral; Feldman, Gregory; Frey, Sharon E.; Launay, Odile; Leroux-Roels, Geert; McElhaney, Janet E.; Nowakowski, Andrzej; Ruiz-Palacios, Guillermo M.; van Essen, Gerrit A.; Oostvogels, Lidia; Devaster, Jeanne-Marie

    2014-01-01

    Estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. This study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (HA) gene-encoded HA1 domain is a simpler alternative to using the conventional hemagglutination inhibition (HI) assay, which requires influenza virus culturing. Specimens were taken from breakthrough cases that occurred in a trivalent influenza virus vaccine efficacy trial involving >43,000 participants during the 2008-2009 season. A total of 498 influenza viruses were successfully subtyped as A(H3N2) (380 viruses), A(H1N1) (29 viruses), B(Yamagata) (23 viruses), and B(Victoria) (66 viruses) from 603 PCR- or culture-confirmed specimens. Unlike the B strains, most A(H3N2) (377 viruses) and all A(H1N1) viruses were classified as homologous to the respective vaccine strains based on their HA1 domain nucleic acid sequence. HI titers relative to the respective vaccine strains and PCR subtyping were determined for 48% (182/380) of A(H3N2) and 86% (25/29) of A(H1N1) viruses. Eighty-four percent of the A(H3N2) and A(H1N1) viruses classified as homologous by sequence were matched to the respective vaccine strains by HI testing. However, these homologous A(H3N2) and A(H1N1) viruses displayed a wide range of relative HI titers. Therefore, although PCR is a sensitive diagnostic method for confirming influenza virus cases, HA1 sequence analysis appeared to be of limited value in accurately predicting antigenicity; hence, it may be inappropriate to classify clinical specimens as homologous or heterologous to the vaccine strain for estimating vaccine efficacy in a prospective clinical trial. PMID:24371255

  2. Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

    PubMed

    Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

    2015-02-01

    Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination. PMID:25566800

  3. Polio Vaccination

    MedlinePlus

    ... inactive polio vaccine OPV=oral polio vaccine Polio Vaccination Pronounced [PO-lee-oh] Recommend on Facebook Tweet ... handling and storage Related Pages Global Vaccines and Immunization Global Polio Also Known As & Abbreviations Polio=poliomyelitis ...

  4. Influenza vaccination: from epidemiological aspects and advances in research to dissent and vaccination policies.

    PubMed

    Gasparini, R; Amicizia, D; Lai, P L; Panatto, D

    2016-01-01

    Influenza is a serious public health problem, since seasonal epidemics affect approximately 5-10% of the population and thus give rise to a heavy social and healthcare burden. The heavy burden of disease is due to several factors, one of which is the biological features of the pathogen. Indeed influenza viruses display high mutation rates and undergo frequent genetic reassortment. Minor variations cause seasonal epidemics and major variations, which result from the hybridization of viruses typical of different animal species, can lead to pandemics. Vaccination remains the most efficacious means of mitigating the harmful healthcare and social effects of influenza. Influenza vaccines have evolved over time in order to offer broader protection against circulating strains. Trivalent vaccines containing two A viruses and one B virus are currently available. However, given the co-circulation of both B virus lineages (B/Yamagata and B/Victoria), quadrivalent vaccines have recently been developed. The new quadrivalent vaccines constitute a great advance, in that they can offer broader strain coverage. Despite the availability of effective and safe influenza vaccines, the Italian public's trust in vaccination has declined and, in the last few years, influenza vaccination coverage rates have decreased both among the elderly and among at-risk adults. It is therefore necessary that users, in their own interests, regain trust in this important means of disease prevention. In order to mitigate the damage wreaked by influenza, it seems important to: (i) improve clinical-epidemiological and virological surveillance of the disease; (ii) promote the development of new efficacious vaccines, as has recently been done through the introduction of the quadrivalent vaccine; (iii) extend free vaccination to the entire population, as in the US and Canada; (iv) ensure that general healthcare professionals are properly informed and always updated with regard to vaccination; (v) promote public

  5. Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine.

    PubMed

    Ovsyannikova, Inna G; Pankratz, V Shane; Vierkant, Robert A; Jacobson, Robert M; Poland, Gregory A

    2006-03-01

    To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and their genotypic combinations to immune status after measles-mumps-rubella (MMR) vaccination, 346 children 12-18 years of age were studied. The class I A*29-Cw*16-B*44 haplotype was associated with lower levels of immunoglobulin G (IgG) antibody to both measles (P=.08) and mumps (P=.03) viral antigens. The A*26-Cw*12-B*38 haplotype was associated with higher cellular immune responses to measles (P=.02) and mumps (P=.01) vaccine viruses. Subjects with the class II DRB1*03-DQB1*02-DPB1*04 haplotype had higher lymphoproliferative responses to measles virus (P=.01) and mumps virus (P=.006). The DRB1*15/16-DQB1*06-DPB1*03 haplotype was associated with high levels of IgG antibody to measles virus (P=.09) but low levels of IgG antibody to rubella virus (P=.02), whereas DRB1*04-DQB1*03-DPB1*03 was associated with high lymphoproliferative responses to both measles (P=.01) and rubella (P=.002) vaccine viruses. A*26-Cw*12-B*38 was associated with both mumps virus-specific humoral (P=.007) and cell-mediated (P=.01) immune responses after 2 doses of MMR vaccine. Haplotype DRB1*04-DQB1*03-DPB1*03 was associated with both lower rubella virus IgG antibody levels (P=.02) and higher rubella virus-specific lymphoproliferation (P=.002). Better characterization of such HLA profiles could inform and improve the design of novel epitope-rich vaccines and help to predict protective immune responses at the individual and population level. PMID:16453260

  6. Immunogenicity against Far Eastern and Siberian subtypes of tick-borne encephalitis (TBE) virus elicited by the currently available vaccines based on the European subtype: systematic review and meta-analysis.

    PubMed

    Domnich, Alexander; Panatto, Donatella; Arbuzova, Eva Klementievna; Signori, Alessio; Avio, Ulderico; Gasparini, Roberto; Amicizia, Daniela

    2014-01-01

    Tick-borne encephalitis (TBE) virus, which is usually divided into European, Far Eastern and Siberian subtypes, is a serious public health problem in several European and Asian countries. Vaccination is the most effective measure to prevent TBE; cross-subtype protection elicited by the TBE vaccines is biologically plausible since all TBE virus subtypes are closely related. This manuscript systematically explores available data on the cross-subtype immunogenicity elicited by the currently available Western vaccines based on the European subtype. Completed immunization course of 3 doses of both Western vaccines determined very high seroconversion/seropositivity rates against both Far Eastern and Siberian subtypes among previously flavivirus-naïve subjects. All but one study found no statistically significant difference in titers of neutralizing antibodies against strains belonging to homologous and heterologous subtypes. Pooled analysis of randomized controlled trials on head-to-head comparison of immunogenicity of Western and Russian TBE vaccines did not reveal differences in seroconversion rates against Far Eastern isolates in either hemagglutination inhibition (risk ratio = 0.98, p = 0.83) or enzyme-linked immunosorbent (risk ratio = 0.95, p = 0.44) assays after 2 vaccine doses. This suggests that, in regions where a heterogeneous TBE virus population circulates, vaccines based on the European subtype may be used alongside vaccines based on the Far Eastern subtype. Studies on the field effectiveness of TBE vaccines and investigation of vaccination failures, especially in countries where different subtypes co-circulate, will further elucidate TBE vaccination-induced cross-subtype protection. PMID:25483679

  7. Update on Veterinary Tuberculosis Vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Educational Objective: At the conclusion of this presentation, the participant will know the current status of veterinary tuberculosis vaccine research and development, and understand the challenges which remain for the future introduction of tuberculosis vaccines intended for wildlife and livestock...

  8. New Vaccines Help Protect You

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues New Vaccines Help Protect You Past Issues / Fall 2006 ... of this page please turn Javascript on. Important new vaccines have recently been approved for use and ...

  9. Potential coverage of circulating HPV types by current and developing vaccines in a group of women in Bosnia and Herzegovina with abnormal Pap smears.

    PubMed

    Salimović-Bešić, I; Hukić, M

    2015-09-01

    The objectives of this study were to identify human papillomavirus (HPV) genotypes in a group of Bosnian-Herzegovinian women with abnormal cytology and to assess their potential coverage by vaccines. HPVs were identified by multiplex real-time PCR test (HPV High Risk Typing Real-TM; Sacace Biotechnologies, Italy) of 105 women with an abnormal cervical Pap smear and positive high-risk (HR) HPV DNA screening test. The most common genotypes in the study were HPV-16 (32·6%, 48/147), HPV-31 (14·3%, 21/147), HPV-51 (9·5%, 14/147) and HPV-18 (7·5%, 11/147). The overall frequency of HR HPV-16 and/or HPV-18, covered by currently available vaccines [Gardasil® (Merck & Co., USA) and Cervarix®; (GlaxoSmithKline, UK)] was lower than the overall frequency of other HPVs detected in the study (40·1%, 59/174, P = 0·017). Group prevalence of HR HPVs targeted by a nine-valent vaccine in development (code-named V503) was higher than total frequency of other HPVs detected (68·0%, 100/147, P < 0·001). Development of cervical cytological abnormalities was independent of the presence of multiple infections (χ 2 = 0·598, P = 0·741). Compared to other HPVs, dependence of cervical diagnosis and HPV-16, -18 (P = 0·008) and HPV-16, -18, -31 (P = 0·008) infections were observed. Vaccines targeting HR HPV-16, -18 and -31 might be an important tool in the prevention of cervical disease in Bosnia and Herzegovina. PMID:25578155

  10. Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.

    PubMed

    Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D

    2015-09-01

    For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised. PMID:24945608

  11. Novel vaccines against influenza viruses

    PubMed Central

    Kang, Sang-Moo; Song, Jae-Min; Compans, Richard W.

    2011-01-01

    Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccination. PMID:21968298

  12. Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

    PubMed

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-01

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process. PMID:26430814

  13. Are current cost-effectiveness thresholds for low- and middle-income countries useful? Examples from the world of vaccines.

    PubMed

    Newall, A T; Jit, M; Hutubessy, R

    2014-06-01

    The World Health Organization's CHOosing Interventions that are Cost Effective (WHO-CHOICE) thresholds for averting a disability-adjusted life-year of one to three times per capita income have been widely cited and used as a measure of cost effectiveness in evaluations of vaccination for low- and middle-income countries (LMICs). These thresholds were based upon criteria set out by the WHO Commission on Macroeconomics and Health, which reflected the potential economic returns of interventions. The CHOICE project sought to evaluate a variety of health interventions at a subregional level and classify them into broad categories to help assist decision makers, but the utility of the thresholds for within-country decision making for individual interventions (given budgetary constraints) has not been adequately explored. To examine whether the 'WHO-CHOICE thresholds' reflect funding decisions, we examined the results of two recent reviews of cost-effectiveness analyses of human papillomavirus and rotavirus vaccination in LMICs, and we assessed whether the results of these studies were reflected in funding decisions for these vaccination programmes. We found that in many cases, programmes that were deemed cost effective were not subsequently implemented in the country. We consider the implications of this finding, the advantages and disadvantages of alternative methods to estimate thresholds, and how cost perspectives and the funders of healthcare may impact on these choices. PMID:24791735

  14. Vaccine hesitancy

    PubMed Central

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  15. [Current situation and ethical-social issues of pediatric genetic testing].

    PubMed

    Yamamoto, Toshiyuki

    2015-11-01

    Many pediatric neurological disorders are caused by genetic factors. Therefore, genetic testing is often required for final diagnosis, prognosis prediction, and genetic counseling. Prior to performing genetic research, pediatric neurologists must obtain the approval of the Institutional Review Board. Moreover, according to the "Ethical Guidelines for Human Genome/Gene Analysis Research," anonymity of patient samples must be maintained. Although the guideline for genetic research are not generally applied for genetic testing in routine bedside medical care, the guideline adopted by the Japan Medical Association must be followed, because genetic information from a personal genome is patient-specific. Pediatric neurologists must also be aware of the policies adopted to obtain informed consent from children and patients who are incapable of making their own decisions. They should develop a strategy for collaboration with clinical geneticists and for making a prenatal diagnosis. PMID:26717641

  16. Vaccinations for Pregnant Women

    PubMed Central

    Swamy, Geeta K.; Heine, R. Phillips

    2014-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician–gynecologists are well-suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease–related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and infant benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and provider resources. PMID:25560127

  17. Vaccinations for pregnant women.

    PubMed

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources. PMID:25560127

  18. Genetic selection for resistance to mycoplasmal pneumonia of swine (MPS) in the Landrace line influences the expression of soluble factors in blood after MPS vaccine sensitization.

    PubMed

    Shimazu, Tomoyuki; Borjigin, Liushiqi; Katayama, Yuki; Li, Meihua; Satoh, Takumi; Watanabe, Kouichi; Kitazawa, Haruki; Roh, Sang-gun; Aso, Hisashi; Kazuo, Katoh; Suda, Yoshihito; Sakuma, Akiko; Nakajo, Mituru; Suzuki, Keiichi

    2014-04-01

    We recently developed a Landrace line that is resistant to mycoplasmal pneumonia of swine (MPS) infection by genetic selection for five generations, and we reported that the immunophenotype of this line is different from that of the non-selected line in terms of changes in peripheral blood leukocyte population after MPS vaccination. This study followed up previous findings demonstrating changes in soluble factors in blood, namely, hormones, Mycoplasma hyopneumoniae-specific immunoglobulin G (IgG), and cytokines. These two lines were injected with MPS vaccine on days -7 and 0 after blood sampling on those days, and blood samples were collected on days -14, -7, 0, 2, 7 and 14. We found changes in the levels of many hormones and cytokines in both lines. However, we found that only growth hormone (GH) and interferon (IFN)-γ levels were statistically different between these two lines. GH concentration was reduced (day 0) and IFN-γ concentration was increased (day 14) in the MPS-selected line compared with the non-selected line, despite unchanged IFN-γ messenger RNA expression in blood cells. Although detailed mechanisms underlying these phenotypes remain unsolved, these traits would be useful to improve MPS resistance in pig production and provide an insight into MPS infection. PMID:24329865

  19. Protective efficacy of reverse genetics based on inactivated American and Asian neuraminidase DIVA marker vaccines against highly pathogenic H5N1 avian influenza viruses in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asian H5N1 highly pathogenic avian influenza has become endemic in several countries, and vaccination is commonly being used. Vaccination can affect surveillance, and therefore there is considerable interest in DIVA (differentiate infected from vaccinated animals) vaccine strategies. Using reverse...

  20. Vaccination Perceptions and Barriers of School Employees: A Pilot Study

    ERIC Educational Resources Information Center

    Luthy, Karlen E.; Houle, Kim; Beckstrand, Renea L.; Macintosh, Janelle; Lakin, Richard G.

    2013-01-01

    Schools are where vaccine-preventable diseases can spread. Vaccination of school children has been studied; however, data are lacking on the vaccination status, perceptions, and barriers to vaccination for school employees. We surveyed school employees' vaccination perceptions, awareness of current vaccination status, and potential barriers…

  1. Rescue of a vaccine strain of peste des petits ruminants virus: In vivo evaluation and comparison with standard vaccine

    PubMed Central

    Muniraju, Murali; Mahapatra, Mana; Buczkowski, Hubert; Batten, Carrie; Banyard, Ashley C.; Parida, Satya

    2015-01-01

    Across the developing world peste des petits ruminants virus places a huge disease burden on agriculture, primarily affecting the production of small ruminant. The disease is most effectively controlled by vaccinating sheep and goats with live attenuated vaccines that provide lifelong immunity. However, the current vaccines and serological tests are unable to enable Differentiation between naturally Infected and Vaccinated Animals (DIVA). This factor precludes meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn reducing the efficiency of control programmes. The availability of a recombinant PPRV vaccine with a proven functionality is a prerequisite for the development of novel vaccines that may enable the development of DIVA tools for PPRV diagnostics. In this study, we have established an efficient reverse genetics system for PPRV Nigeria 75/1 vaccine strain and, further rescued a version of PPRV Nigeria 75/1 vaccine strain that expresses eGFP as a novel transcription cassette and a version of PPRV Nigeria 75/1 vaccine strain with mutations in the haemagglutinin (H) gene to enable DIVA through disruption of binding to H by the C77 monoclonal antibody used in the competitive (c) H-ELISA. All three rescued viruses showed similar growth characteristics in vitro in comparison to parent vaccine strain and, following in vivo assessment the H mutant provided full protection in goats. Although the C77 monoclonal antibody used in the cH-ELISA was unable to bind to the mutated form of H in vitro, the mutation was not sufficient to enable DIVA in vivo. PMID:25444790

  2. Rescue of a vaccine strain of peste des petits ruminants virus: In vivo evaluation and comparison with standard vaccine.

    PubMed

    Muniraju, Murali; Mahapatra, Mana; Buczkowski, Hubert; Batten, Carrie; Banyard, Ashley C; Parida, Satya

    2015-01-01

    Across the developing world peste des petits ruminants virus places a huge disease burden on agriculture, primarily affecting the production of small ruminant. The disease is most effectively controlled by vaccinating sheep and goats with live attenuated vaccines that provide lifelong immunity. However, the current vaccines and serological tests are unable to enable Differentiation between naturally Infected and Vaccinated Animals (DIVA). This factor precludes meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn reducing the efficiency of control programmes. The availability of a recombinant PPRV vaccine with a proven functionality is a prerequisite for the development of novel vaccines that may enable the development of DIVA tools for PPRV diagnostics. In this study, we have established an efficient reverse genetics system for PPRV Nigeria 75/1 vaccine strain and, further rescued a version of PPRV Nigeria 75/1 vaccine strain that expresses eGFP as a novel transcription cassette and a version of PPRV Nigeria 75/1 vaccine strain with mutations in the haemagglutinin (H) gene to enable DIVA through disruption of binding to H by the C77 monoclonal antibody used in the competitive (c) H-ELISA. All three rescued viruses showed similar growth characteristics in vitro in comparison to parent vaccine strain and, following in vivo assessment the H mutant provided full protection in goats. Although the C77 monoclonal antibody used in the cH-ELISA was unable to bind to the mutated form of H in vitro, the mutation was not sufficient to enable DIVA in vivo. PMID:25444790

  3. Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions.

    PubMed

    Wang, Guangchuan; Cao, Rui-Yuan; Chen, Rong; Mo, Lijuan; Han, Jian-Feng; Wang, Xiaoyu; Xu, Xurong; Jiang, Tao; Deng, Yong-Qiang; Lyu, Ke; Zhu, Shun-Ya; Qin, E-De; Tang, Ruikang; Qin, Cheng-Feng

    2013-05-01

    The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26 °C for more than 9 d and at 37 °C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures. PMID:23589862

  4. Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions

    PubMed Central

    Wang, Guangchuan; Cao, Rui-Yuan; Chen, Rong; Mo, Lijuan; Han, Jian-Feng; Wang, Xiaoyu; Xu, Xurong; Jiang, Tao; Deng, Yong-Qiang; Lyu, Ke; Zhu, Shun-Ya; Tang, Ruikang; Qin, Cheng-Feng

    2013-01-01

    The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26 °C for more than 9 d and at 37 °C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures. PMID:23589862

  5. Vaccines for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  6. Governments, off-patent vaccines, smallpox and universal childhood vaccination.

    PubMed

    Music, Stanley

    2010-01-22

    WHO is now celebrating more than 30 years of freedom from smallpox. What was originally seen as a victory over an ancient scourge can now be viewed as an epidemiologically driven programme to overcome governmental inertia and under-achievement in delivering an off-patent vaccine. Though efforts are accelerating global vaccine use, a plea is made to push the world's governments to commit to universal childhood vaccination via a proposed new programme. The latter should begin by exploiting a long list of ever more affordable off-patent vaccines, vaccines that can virtually eliminate the bulk of the world's current vaccine-preventable disease burden. PMID:19699330

  7. How Genetics Might Affect Real Property Rights: Currents in Contemporary Bioethics.

    PubMed

    Rothstein, Mark A; Rothstein, Laura

    2016-03-01

    New developments in genetics could affect a variety of real property rights. Mortgage lenders, mortgage insurers, real estate sellers, senior living centers, retirement communities, or other parties in residential real estate transactions begin requiring predictive genetic information as part of the application process. One likely use would be by retirement communities to learn an individual's genetic risk for Alzheimer's disease. The federal Fair Housing Act prohibits discrimination based on disability, but it is not clear that it would apply to genetic risk assessments. Only California law explicitly applies to this situation and there have been no reported cases. PMID:27256137

  8. [Current status in the commercialization and application of genetically modified plants and their effects on human and livestock health and phytoremediation].

    PubMed

    Yoshimatsu, Kayo; Kawano, Noriaki; Kawahara, Nobuo; Akiyama, Hiroshi; Teshima, Reiko; Nishijima, Masahiro

    2012-01-01

    Developments in the use of genetically modified plants for human and livestock health and phytoremediation were surveyed using information retrieved from Entrez PubMed, Chemical Abstracts Service, Google, congress abstracts and proceedings of related scientific societies, scientific journals, etc. Information obtained was classified into 8 categories according to the research objective and the usage of the transgenic plants as 1: nutraceuticals (functional foods), 2: oral vaccines, 3: edible curatives, 4: vaccine antigens, 5: therapeutic antibodies, 6: curatives, 7: diagnostic agents and reagents, and 8: phytoremediation. In total, 405 cases were collected from 2006 to 2010. The numbers of cases were 120 for nutraceuticals, 65 for oral vaccines, 25 for edible curatives, 36 for vaccine antigens, 36 for therapeutic antibodies, 76 for curatives, 15 for diagnostic agents and reagents, and 40 for phytoremediation (sum of each cases was 413 because some reports were related to several categories). Nutraceuticals, oral vaccines and curatives were predominant. The most frequently used edible crop was rice (51 cases), and tomato (28 cases), lettuce (22 cases), potato (18 cases), corn (15 cases) followed. PMID:22687699

  9. Inactivated or live-attenuated bivalent vaccines that confer protection against rabies and Ebola viruses.

    PubMed

    Blaney, Joseph E; Wirblich, Christoph; Papaneri, Amy B; Johnson, Reed F; Myers, Carey J; Juelich, Terry L; Holbrook, Michael R; Freiberg, Alexander N; Bernbaum, John G; Jahrling, Peter B; Paragas, Jason; Schnell, Matthias J

    2011-10-01

    The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas. PMID:21849459

  10. Inactivated or Live-Attenuated Bivalent Vaccines That Confer Protection against Rabies and Ebola Viruses ▿

    PubMed Central

    Blaney, Joseph E.; Wirblich, Christoph; Papaneri, Amy B.; Johnson, Reed F.; Myers, Carey J.; Juelich, Terry L.; Holbrook, Michael R.; Freiberg, Alexander N.; Bernbaum, John G.; Jahrling, Peter B.; Paragas, Jason; Schnell, Matthias J.

    2011-01-01

    The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas. PMID:21849459

  11. International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs.

    PubMed

    Hülsmeyer, Velia-Isabel; Fischer, Andrea; Mandigers, Paul J J; DeRisio, Luisa; Berendt, Mette; Rusbridge, Clare; Bhatti, Sofie F M; Pakozdy, Akos; Patterson, Edward E; Platt, Simon; Packer, Rowena M A; Volk, Holger A

    2015-01-01

    Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management of the dog with epilepsy in everyday clinical practice and furthermore may promote canine epilepsy research. The following manuscript reviews the evidence available for breeds which have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background, and highlights different breed specific clinical features (e.g. age at onset, sex, seizure type), treatment response, prevalence rates and proposed inheritance reported in the literature. In addition, certain breed-specific diseases that may act as potential differentials for idiopathic epilepsy are highlighted. PMID:26316206

  12. Development of vaccines against influenza A virus (H5N1).

    PubMed

    Li, Wen-Chen; Huang, Yhu-Chering

    2007-01-01

    Three influenza pandemics took place during the 20th century, including the 1918 pandemic, which killed an estimated 50 million people. We are facing the threat of another pandemic, which may be caused by an A/H5N1 influenza virus. These viruses have expanded their territory from Asia to the Middle East, Africa and Europe and have caused more than 190 human deaths up to the present. Vaccines in response to this pandemic threat are currently under development. Reverse-genetics-based inactivated whole-virion vaccines and adjuvanted split-virion vaccines are undergoing clinical trials and are among possible candidates to be approved as H5N1 vaccines for human beings. Problems, including low immunogenicity in the generally naive human population, a lack of data on these vaccines in relation to immunocompromised Dr. Yhu-Chering Huang patients, young children and the elderly and the currently limited global capacity to manufacture influenza vaccines, all need to be resolved. Several innovative approaches, such as the use of novel adjuvants, an antigen-sparing policy and the use of adenoviral-vector-based or DNA vaccines, are being used to develop more efficient vaccines. Every effort should be made to shorten the gap that remains and improve greatly influenza pandemic vaccine access. PMID:17939259

  13. Mucosal delivery of vaccines.

    PubMed

    Del Giudice, G; Pizza, M; Rappuoli, R

    1999-09-01

    Oral delivery represents one of the most pursued approaches for large-scale human vaccination. Due to the different characteristics of mucosal immune response, as compared with systemic response, oral immunization requires particular methods of antigen preparation and selective strategies of adjuvanticity. In this paper, we describe the preparation and use of genetically detoxified bacterial toxins as mucosal adjuvants and envisage the possibility of their future exploitation for human oral vaccines. PMID:10525451

  14. The Role of the Family in Genetic Testing: Theoretical Perspectives, Current Knowledge, and Future Directions

    ERIC Educational Resources Information Center

    Peterson, Susan K.

    2005-01-01

    This article addresses conceptual challenges and theoretical approaches for examining the role of the family in responding and adapting to genetic testing for inherited conditions. Using a family systems perspective, family-based constructs that are relevant to genetic testing may be organized into three domains: family communication, organization…

  15. Vaccine-preventable disease and immunization in the developing world.

    PubMed

    Bart, K J; Lin, K F

    1990-06-01

    Vaccines have given health care providers control over a substantial portion of the morbidity and mortality in the developing world. Global efforts have immunized two-thirds of the world's children with DTP and polio vaccines; 72% have received BCG and 59% measles vaccine; but only 29% of pregnant women have received two doses of tetanus toxoid. In addition, vaccines against yellow fever, Japanese encephalitis, hepatitis B, rubella, and mumps and meningococcal polysaccharide vaccine are being used in specific regions of the world. New vaccine candidates will enhance the vaccine armamentarium over the next decade to include the causes of pneumonia, diarrhea, and meningitis: Haemophilus influenzae type b, pneumococcal and meningococcal protein conjugate vaccines, typhoid and rotavirus vaccine. Genetically engineered vaccine vehicles, genetic reassortants, and genetic deletions are being investigated as new vaccine candidates. PMID:2190145

  16. Current landscape of direct-to-consumer genetic testing and its role in ophthalmology: a review.

    PubMed

    Sanfilippo, Paul G; Kearns, Lisa S; Wright, Philip; Mackey, David A; Hewitt, Alex W

    2015-08-01

    The sequencing of the human genome has seen the emergence of the direct-to-consumer (DTC) genetic-testing market, which allows individuals to obtain information about their genetic profile and its many health and lifestyle implications. Genetics play an important role in the development of many eye diseases, however, little information is available describing the influence of the DTC industry in ophthalmology. In this review, we examined DTC companies providing genetic test products for eye disease. Of all eye conditions, the majority of DTC companies provided susceptibility testing or risk assessment for age-related macular degeneration (AMD). For the 15 companies noted to offer products, we found considerable variation in the cost, scope and clarity of informational content of DTC genetic testing for ophthalmic conditions. The clinical utility of these tests remains in question, and the American Academy of Ophthalmology recommendations against routine testing for many conditions probably still apply. PMID:25676199

  17. The Danish vaccination register.

    PubMed

    Grove Krause, T; Jakobsen, S; Haarh, M; Mølbak, K

    2012-01-01

    Immunisation information systems (IIS) are valuable tools for monitoring vaccination coverage and for estimating vaccine effectiveness and safety. Since 2009, an advanced IIS has been developed in Denmark and will be implemented during 2012–14. This IIS is based on a database existing since 2000. The reporting of all administered vaccinations including vaccinations outside the national programme will become mandatory. Citizens will get access to data about their own vaccinations and healthcare personnel will get access to information on the vaccinations of their patients. A national concept of identification, a national solution combining a personal code and a card with codes, ensures easy and secure access to the register. From the outset, the IIS will include data on childhood vaccinations administered from 1996 and onwards. All Danish citizens have a unique identifier, a so called civil registration number, which allows the linking of information on vaccinations coming from different electronic data sources. The main challenge will be to integrate the IIS with the different electronic patient record systems currently existing at general practitioner, vaccination clinic and hospital level thereby avoiding double-entry. A need has been identified for an updated international classification of vaccine products on the market. Such a classification would also be useful for the future exchange of data on immunisations from IIS between countries. PMID:22551494

  18. Nasal vaccine innovation.

    PubMed

    Jabbal-Gill, Inderjit

    2010-12-01

    The current vaccine market is gaining momentum in the development of alternative administration routes namely intranasal, oral, topical, pulmonary, vaginal, and rectal; the nasal route offers the most promising opportunity for vaccine administration. It can enhance convenience, safety, elicit both local and systemic immune responses; thus potentially provide protection from pathogens at the site of entry. Nasal vaccine innovation comes with both opportunities and challenges. The innovative strategies used by industry and researchers to overcome the hurdles are discussed in this article: these include live-attenuated vaccines, adjuvants, mucoadhesives, particulate delivery systems, virus-like particles, vaccine manufacture, challenges of regulatory authorities, and the nasal vaccine impact on market potential. Critical issues for effective nasal vaccination are the antigen-retention period that enables its interaction with the lymphatic system and choice of an adjuvant that is nontoxic and induces the required immune response. Co-adjuvanting by means of a mucoadhesive technology addresses some of these issues. ChiSys(®), a natural bioadhesive with proven intranasal safety profile, has already demonstrated efficacy for several nasally delivered vaccines including norovirus. With the looming threat of a pandemic, alternatives such as intranasal vaccination will ultimately facilitate greater public compliance and rapid mass global vaccination. PMID:21047271

  19. Clinical Impact of Vaccine Development.

    PubMed

    Nambiar, Puja H; Daza, Alejandro Delgado; Livornese, Lawrence L

    2016-01-01

    The discovery and development of immunization has been a singular improvement in the health of mankind. This chapter reviews currently available vaccines, their historical development, and impact on public health. Specific mention is made in regard to the challenges and pursuit of a vaccine for the human immunodeficiency virus as well as the unfounded link between autism and measles vaccination. PMID:27076123

  20. DNA vaccines in veterinary use

    PubMed Central

    Redding, Laurel; Werner, David B

    2015-01-01

    DNA vaccines represent a new frontier in vaccine technology. One important application of this technology is in the veterinary arena. DNA vaccines have already gained a foothold in certain fields of veterinary medicine. However, several important questions must be addressed when developing DNA vaccines for animals, including whether or not the vaccine is efficacious and cost effective compared with currently available options. Another important question to consider is how to apply this developing technology in a wide range of different situations, from the domestic pet to individual fish in fisheries with several thousand animals, to wildlife programs for disease control. In some cases, DNA vaccines represent an interesting option for vaccination, while in others, currently available options are sufficient. This review will examine a number of diseases of veterinary importance and the progress being made in DNA vaccine technology relevant to these diseases, and we compare these with the conventional treatment options available. PMID:19722897

  1. Chikungunya vaccines in development

    PubMed Central

    Schwameis, Michael; Buchtele, Nina; Wadowski, Patricia Pia; Schoergenhofer, Christian; Jilma, Bernd

    2016-01-01

    ABSTRACT Chikungunya virus has become a global health threat, spreading to the industrial world of Europe and the Americas; no treatment or prophylactic vaccine is available. Since the late 1960s much effort has been put into the development of a vaccine, and several heterogeneous strategies have already been explored. Only two candidates have recently qualified to enter clinical phase II trials, a chikungunya virus-like particle-based vaccine and a recombinant live attenuated measles virus-vectored vaccine. This review focuses on the current status of vaccine development against chikungunya virus in humans and discusses the diversity of immunization strategies, results of recent human trials and promising vaccine candidates. PMID:26554522

  2. Anthrax vaccination strategies

    PubMed Central

    Cybulski, Robert J.; Sanz, Patrick; O'Brien, Alison D.

    2009-01-01

    The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies. PMID:19729034

  3. Genetic manipulation of francisella tularensis.

    PubMed

    Zogaj, Xhavit; Klose, Karl E

    2010-01-01

    Francisella tularensis is a facultative intracellular pathogen that causes the disease tularemia. F. tularensis subsp. tularensis causes the most severe disease in humans and has been classified as a Category A select agent and potential bioweapon. There is currently no vaccine approved for human use, making genetic manipulation of this organism critical to unraveling the genetic basis of pathogenesis and developing countermeasures against tularemia. The development of genetic techniques applicable to F. tularensis have lagged behind those routinely used for other bacteria, primarily due to lack of research and the restricted nature of the biocontainment required for studying this pathogen. However, in recent years, genetic techniques, such as transposon mutagenesis and targeted gene disruption, have been developed, that have had a dramatic impact on our understanding of the genetic basis of F. tularensis virulence. In this review, we describe some of the methods developed for genetic manipulation of F. tularensis. PMID:21607086

  4. Genetic Manipulation of Francisella Tularensis

    PubMed Central

    Zogaj, Xhavit; Klose, Karl E.

    2011-01-01

    Francisella tularensis is a facultative intracellular pathogen that causes the disease tularemia. F. tularensis subsp. tularensis causes the most severe disease in humans and has been classified as a Category A select agent and potential bioweapon. There is currently no vaccine approved for human use, making genetic manipulation of this organism critical to unraveling the genetic basis of pathogenesis and developing countermeasures against tularemia. The development of genetic techniques applicable to F. tularensis have lagged behind those routinely used for other bacteria, primarily due to lack of research and the restricted nature of the biocontainment required for studying this pathogen. However, in recent years, genetic techniques, such as transposon mutagenesis and targeted gene disruption, have been developed, that have had a dramatic impact on our understanding of the genetic basis of F. tularensis virulence. In this review, we describe some of the methods developed for genetic manipulation of F. tularensis. PMID:21607086

  5. Smallpox Vaccination

    MedlinePlus

    ... Newsletters Events Also Known As Smallpox = Vaccinia Smallpox Vaccination Recommend on Facebook Tweet Share Compartir The smallpox ... like many other vaccines. For that reason, the vaccination site must be cared for carefully to prevent ...

  6. HPV vaccine

    MedlinePlus

    Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... and Gynecologists. Committee Opinion No. 588: Human Papillomavirus Vaccination. Obstet Gynecol . 2014;123(3):712-8. PMID: ...

  7. The Meningitis Vaccine Project.

    PubMed

    LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

    2007-09-01

    Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world. PMID:17521780

  8. Footrot vaccines and vaccination.

    PubMed

    Dhungyel, Om; Hunter, James; Whittington, Richard

    2014-05-30

    Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of

  9. Influenza Vaccines: Unmet Needs and Recent Developments

    PubMed Central

    Noh, Ji Yun

    2013-01-01

    Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described. PMID:24475351

  10. Addressing the vaccine confidence gap.

    PubMed

    Larson, Heidi J; Cooper, Louis Z; Eskola, Juhani; Katz, Samuel L; Ratzan, Scott

    2011-08-01

    Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines. PMID:21664679

  11. Viral vaccines for bony fish: past, present and future.

    PubMed

    Salgado-Miranda, Celene; Loza-Rubio, Elizabeth; Rojas-Anaya, Edith; García-Espinosa, Gary

    2013-05-01

    Since 1970, aquaculture production has grown. In 2010, it had an annual average rate of 6.3% with 59.9 million tons of product and soon could exceed capture fisheries as a source of fishery products. However, the occurrence of viral diseases continues to be a significant limiting factor and its control is important for the development of this sector. In aquaculture farms, fish are reared under intensive culture conditions, and the use of viral vaccines has enabled an increase in production. Several types of vaccines and strategies of vaccination have been developed; however, this approach has not reached the expected goals in the most susceptible stage (fingerlings). Currently, there are inactivated and recombinant commercial vaccines, mainly for salmonids and cyprinids. In addition, updated genomic and proteomic technology has expedited the research and expansion of new vaccine models, such as those comprised of subunits or DNA. The objective of this review is to cover the various types of viral vaccines that have been developed and are available for bony fishes, as well as the advantages and challenges that DNA vaccines present for massive administration in a growing aquaculture, possible risks for the environment, the controversy regarding genetically modified organisms and possible acceptance by consumers. PMID:23659303

  12. Manipulation of BCG vaccine: a double-edged sword.

    PubMed

    Singh, V K; Srivastava, R; Srivastava, B S

    2016-04-01

    Mycobacterium bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach. PMID:26810060

  13. Effect of recombinant canine distemper vaccine on antibody titers in previously vaccinated dogs.

    PubMed

    Larson, L J; Hageny, T L; Haase, C J; Schultz, R D

    2006-01-01

    Two canine distemper virus (CDV) vaccine types are currently commercially available: modified-live virus (MLV) vaccines and a canarypox recombinant CDV (rCDV) vaccine (Recombitek, Merial). This study compared the ability of the rCDV vaccine and MLV vaccines to significantly enhance (boost) the antibody response of previously immunized adult and juvenile dogs. A significant (fourfold or greater) increase in titer occurred in significantly more dogs revaccinated with Recombitek C-4 or Recombitek C-6 than with the MLV-CDV vaccines. This study demonstrates that Recombitek, the only vaccine for dogs containing rCDV, is more likely to significantly boost the CDV antibody response in previously vaccinated dogs than are the MLV-CDV vaccines. Because rCDV vaccine can boost the antibody titer of dogs previously vaccinated with an MLV vaccine, it can and should be used when core vaccines are readministered. PMID:16871492

  14. Vaccine Hesitancy.

    PubMed

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. PMID:26541249

  15. Toward altering milk composition by genetic manipulation: current status and challenges.

    PubMed

    Karatzas, C N; Turner, J D

    1997-09-01

    The implementation of large-scale genome mapping and sequencing has improved the understanding of animal genetics. A large number of gene sequences are now available to serve as regulatory elements or genes of interest. Although the central thrust of this work is focused on understanding disease states, the manipulation of normal metabolic processes is feasible. To date, the genetic manipulation of livestock has been limited to the permanent addition of genes of clinical interest. This study explores the utility of genetically engineered cattle as a means of altering milk composition to improve the functional properties of milk, increasing marketability. Improvements would include increasing the concentration of valuable components in milk (e.g., casein), removing undesirable components (e.g., lactose), or altering composition to resemble that of human milk as a means of improving human neonatal nutrition. The protracted time lines of genetically modifying dairy cattle has prompted the development of animal models. A model for dwarf goats is discussed in terms of circumventing the lengthy time lines involved in generating transgenic cattle and allowing for an accelerated expansion of research in molecular genetics of dairy animals. Thus, the genetic manipulation of dairy cattle is feasible and could have significant impacts on milk quality, attributes of novel dairy products, and human health. PMID:9313168

  16. Immunogenicity studies with a genetically engineered hexavalent PorA and a wild-type meningococcal group B outer membrane vesicle vaccine in infant cynomolgus monkeys.

    PubMed

    Rouppe van der Voort, E; Schuller, M; Holst, J; de Vries, P; van der Ley, P; van den Dobbelsteen, G; Poolman, J

    2000-01-31

    The immunogenicity of two meningococcal outer membrane vesicle (OMV) vaccines, namely the Norwegian wild-type OMV vaccine and the Dutch hexavalent PorA OMV vaccine, were examined in infant cynomolgus monkeys. For the first time, a wild-type- and a recombinant OMV vaccine were compared. Furthermore, the induction of memory and the persistence of circulating antibodies were measured. The Norwegian vaccine contained all four classes of major outer membrane proteins (OMP) and wild-type L3/L8 lipopolysaccharide (LPS). The Dutch vaccine consisted for 90% of class 1 OMPs, had low expression of class 4 and 5 OMP, and GalE LPS. Three infant monkeys were immunised with a human dose at the age of 1.5, 2.5 and 4.5 months. Two monkeys of each group received a fourth dose at the age of 11 months. In ELISA, both OMV vaccines were immunogenic and induced booster responses, particularly after the fourth immunisation. The Norwegian vaccine mostly induced sero-subtype P1.7,16 specific serum bactericidal antibodies (SBA), although some other SBA were induced as well. The antibody responses against P1.7,16, induced by the Norwegian vaccine, were generally higher than for the Dutch vaccine. However, the Dutch vaccine induced PorA specific SBA against all six sero-subtypes included in the vaccine showing differences in the magnitude of SBA responses to the various PorAs. PMID:10618530

  17. Autism and measles-mumps-rubella vaccination: controversy laid to rest?

    PubMed

    DeStefano, F; Chen, R T

    2001-01-01

    It has been suggested that vaccination, particularly with measles-mumps-rubella (MMR) vaccine, may be related to the development of autism. The main evidence for a possible association is that the prevalence of autism has been increasing at the same time that infant vaccination coverage has increased, and that in some cases there is an apparent temporal association in which autistic characteristics are first noted shortly after vaccination. Although the prevalence of autism and similar disorders appears to have increased recently, it is not clear if this is an actual increase or the result of increased recognition and changes in diagnostic criteria. The apparent onset of autism in close proximity to vaccination may be a coincidental temporal association. The clinical evidence in support of an association derives from a series of 12 patients with inflammatory bowel conditions and regressive developmental disorders, mostly autism. The possibility that measles vaccine may cause autism through a persistent bowel infection has generated much interest, since it provides a possible biological mechanism. Epidemiological studies, however, have not found an association between MMR vaccination and autism. The epidemiological findings are consistent with current understanding of the pathogenesis of autism, which has a strong genetic component and in which the neurological defects probably occur early in embryonic development. It seems unlikely that a vaccination that is given after birth could cause autism. A minority of cases of autism may have onset after 1 year of age (regressive autism), but the single epidemiological study that included such cases did not find an association with MMR vaccination. Currently, the weight of the available epidemiological and related evidence does not support a causal association between MMR vaccine, or any other vaccine or vaccine constituent, and autism. PMID:11700148

  18. Genetic counselors' current use of personal health records-based family histories in genetic clinics and considerations for their future adoption.

    PubMed

    Widmer, Chaney; Deshazo, Jonathan P; Bodurtha, Joann; Quillin, John; Creswick, Heather

    2013-06-01

    Given the widespread adoption of electronic medical records and recent emergence of electronic family history tools, we examined genetic counselors' perspectives on the emerging technology of the personal health record (PHR)-based family history tool that links to an electronic medical record (EMR). Two-hundred thirty-three genetic counselors responded to an on-line survey eliciting current use of electronic family history (EFH) tools and familiarity with PHR-based family history tools. Additionally, after being shown a series of screen shots of a newly developed PHR-based family history tool based on the U.S. Surgeon General's My Family Health Portrait (United States Department of Health and Human Services 2009), participants were surveyed about the perceived usefulness, ease of use, and impact on current workflow that this kind of tool would have in their practices. Eighty-three percent reported that their institution has an EMR, yet only 35 % have a dedicated space for family history. Eighty-two percent reported that less than 5 % of their patients have a PHR, and only 16 % have worked with patients who have a PHR. Seventy-two percent or more agreed that a PHR-based family history tool would facilitate communication, increase accuracy of information, ensure consistency in recording information, increase focus on actual counseling, reduce repetitive questions, improve efficiency, and increase the legibility and clarity. Our findings suggest that participants were familiar with existing EFH tools, but that the majority did not use them in practice. Genetic counselors' adoption of such tools is limited due to non-existence of this kind of technology or inability to integrate it into their clinics. They are also strongly in favor of adopting a PHR-based family history tool in genetics clinics, but have practical concerns that must be addressed before the tool can be implemented. PMID:23242928

  19. Multigenic Control of Measles Vaccine Immunity Mediated by Polymorphisms in Measles Receptor, Innate Pathway, and Cytokine Genes

    PubMed Central

    Kennedy, Richard B.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; O’Byrne, Megan; Jacobson, Robert M.; Pankratz, V. Shane; Poland, Gregory A.

    2012-01-01

    Measles infection and vaccine response are complex biological processes that involve both viral and host genetic factors. We have previously investigated the influence of genetic polymorphisms on vaccine immune response, including measles vaccines, and have shown that polymorphisms in HLA, cytokine, cytokine receptor, and innate immune response genes are associated with variation in vaccine response but do not account for all of the inter-individual variance seen in vaccinated populations. In the current study we report the findings of a multigenic analysis of measles vaccine immunity, indicating a role for the measles virus receptor CD46, innate pattern-recognition receptors (DDX58, TLR2, 4, 5,7 and 8) and intracellular signaling intermediates (MAP3K7, NFKBIA), and key antiviral molecules (VISA, OAS2, MX1, PKR) as well as cytokines (IFNA1, IL4, IL6, IL8, IL12B) and cytokine receptor genes (IL2RB, IL6R, IL8RA) in the genetic control of both humoral and cellular immune responses. This multivariate approach provided additional insights into the genetic control of measles vaccine responses over and above the information gained by our previous univariate SNP association analyses. PMID:22265947

  20. Vaccine process technology.

    PubMed

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  1. Implications of genetics and current protected areas for conservation of 5 endangered primates in China.

    PubMed

    Liu, Zhijin; Liu, Guangjian; Roos, Christian; Wang, Ziming; Xiang, ZuoFu; Zhu, Pingfen; Wang, Boshi; Ren, Baoping; Shi, Fanglei; Pan, Huijuan; Li, Ming

    2015-12-01

    Most of China's 24-28 primate species are threatened with extinction. Habitat reduction and fragmentation are perhaps the greatest threats. We used published data from a conservation genetics study of 5 endangered primates in China (Rhinopithecus roxellana, R. bieti, R. brelichi, Trachypithecus francoisi, and T. leucocephalus); distribution data on these species; and the distribution, area, and location of protected areas to inform conservation strategies for these primates. All 5 species were separated into subpopulations with unique genetic components. Gene flow appeared to be strongly impeded by agricultural land, meadows used for grazing, highways, and humans dwellings. Most species declined severely or diverged concurrently as human population and crop land cover increased. Nature reserves were not evenly distributed across subpopulations with unique genetic backgrounds. Certain small subpopulations were severely fragmented and had higher extinction risk than others. Primate mobility is limited and their genetic structure is strong and susceptible to substantial loss of diversity due to local extinction. Thus, to maximize preservation of genetic diversity in all these primate species, our results suggest protection is required for all sub-populations. Key priorities for their conservation include maintaining R. roxellana in Shennongjia national reserve, subpopulations S4 and S5 of R. bieti and of R. brelichi in Fanjingshan national reserve, subpopulation CGX of T. francoisi in central Guangxi Province, and all 3 T. leucocephalus sub-populations in central Guangxi Province. PMID:26372167

  2. Genetics Show Current Decline and Pleistocene Expansion in Northern Spotted Owls

    USGS Publications Warehouse

    Funk, W. Chris; Forsman, Eric D.; Mullins, Thomas D.; Haig, Susan M.

    2008-01-01

    The northern spotted owl (Strix occidentalis caurina) is one of the most controversial threatened subspecies ever listed under the U.S. Endangered Species Act. Because of concern for persistence of the subspecies, logging on Federal lands in the U.S. Pacific Northwest was dramatically reduced under the Northwest Forest Plan in 1994. Despite protection of its remaining forest habitat, recent field studies show continued demographic declines of northern spotted owls. One potential threat to northern spotted owls that has not yet been shown is loss of genetic variation from population bottlenecks that can increase inbreeding depression and decrease adaptive potential. Here, we show recent genetic bottlenecks in northern spotted owls using a large genetic dataset (352 individuals from across the subspecies' range and 11 microsatellite loci). The signature of bottlenecks was strongest in Washington State, in agreement with field data. Interestingly, we also found a genetic signature of Pleistocene expansion in the same study areas where recent bottlenecks were shown. Our results provide independent evidence that northern spotted owls have recently declined, and suggest that loss of genetic variation is an emerging threat to the subspecies' persistence. Reduced effective population size (Ne), shown here in addition to field evidence for demographic decline, highlights the increasing vulnerability of this bird to extinction.

  3. Comparative Antitumor Effect of Preventive versus Therapeutic Vaccines Employing B16 Melanoma Cells Genetically Modified to Express GM-CSF and B7.2 in a Murine Model

    PubMed Central

    Miguel, Antonio; Herrero, María José; Sendra, Luis; Botella, Rafael; Algás, Rosa; Sánchez, Maria; Aliño, Salvador F.

    2012-01-01

    Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing B16 tumor cells expressing GM-CSF and B7.2. Wild B16 cells were injected in C57BL6 mice to cause the tumor. Irradiated B16 cells transfected with GM-CSF, B7.2, or both, were processed as a preventive and therapeutic vaccination. Tumor volumes were measured and survival curves were obtained. Blood samples were taken from mice, and IgGs of each treatment group were also measured. The regulatory T cells (Treg) of selected groups were quantified using counts of images taken by confocal microscopy. Results: one hundred percent survival was achieved by preventive vaccination with the group of cells transfected with p2F_GM-CSF. Therapeutic vaccination achieved initial inhibition of tumor growth but did not secure overall survival of the animals. Classical Treg cells did not vary among the different groups in this therapeutic vaccination model. PMID:23202306

  4. Dendritic cell-based cancer therapeutic vaccines

    PubMed Central

    Palucka, Karolina; Banchereau, Jacques

    2013-01-01

    The past decade has seen tremendous developments in novel cancer therapies, through targeting of tumor cell-intrinsic pathways whose activity is linked to genetic alterations, as well as the targeting of tumor cell-extrinsic factors such as growth factors. Furthermore, immunotherapies are entering the clinic at an unprecedented speed following the demonstration that T cells can efficiently reject tumors and that their anti-tumor activity can be enhanced with antibodies against immune regulatory molecules (checkpoints blockade). Current immunotherapy strategies include monoclonal antibodies against tumor cells or immune regulatory molecules, cell-based therapies such as adoptive transfer of ex vivo activated T cells and natural killer (NK) cells, and cancer vaccines. Herein, we discuss the immunological basis for therapeutic cancer vaccines and how the current understanding of dendritic cell (DC) and T cell biology might enable development of next-generation curative therapies for patients with cancer. PMID:23890062

  5. Dengue virus vaccine development.

    PubMed

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches. PMID:24373316

  6. Polyvalent AIDS Vaccines

    PubMed Central

    Lu, Shan; Grimes Serrano, Jill M.; Wang, Shixia

    2013-01-01

    A major hurdle in the development of a global HIV-1 vaccine is viral diversity. For close to three decades, HIV vaccine development has focused on either the induction of T cell immune responses or antibody responses, and only rarely on both components. After the failure of the STEP trial, the scientific community concluded that a T cell-based vaccine would likely not be protective if the T cell immune responses were elicited against only a few dominant epitopes. Similarly, for vaccines focusing on antibody responses, one of the main criticisms after VaxGen’s failed Phase III trials was on the limited antigen breadth included in the two formulations used. The successes of polyvalent vaccine approaches against other antigenically variable pathogens encourage implementation of the same approach for the design of HIV-1 vaccines. A review of the existing HIV-1 vaccination approaches based on the polyvalent principle is included here to provide a historical perspective for the current effort of developing a polyvalent HIV-1 vaccine. Results summarized in this review provide a clear indication that the polyvalent approach is a viable one for the future development of an effective HIV vaccine. PMID:21054250

  7. Bovine herpesvirus-1: evaluation of genetic diversity of subtypes derived from field strains of varied clinical syndromes and their relationship to vaccine strains.

    PubMed

    Fulton, R W; d'Offay, J M; Eberle, R; Moeller, R B; Campen, H Van; O'Toole, D; Chase, C; Miller, M M; Sprowls, R; Nydam, D V

    2015-01-15

    Bovine herpesvirus-1 (BoHV-1) causes significant disease in cattle. Control programs in North America incorporate vaccination with modified live viral (MLV) or killed (KV) vaccine. BoHV-1 strains are isolated from diseased animals or fetuses after vaccination. There are markers for differentiating MLV from field strains using whole-genome sequencing and analysis identifying single nucleotide polymorphisms (SNPs). Using multiple primer sets and sequencing of products permits association of BoHV-1 isolates with vaccines. To determine association between vaccine virus and strains isolated from clinical cases following vaccination, we analyzed 12 BoHV-1 isolates from animals with various clinical syndromes; 9 corresponded to BoHV-1.1 respiratory group. The remaining three corresponded to BoHV-1.2b, typically found in genital tracts of cattle. Four BoHV-1 isolates were identical to a vaccine strain; three were from post-vaccination abortion episodes with typical herpetic lesions whose dams had received MLV vaccine during pregnancy, and one from a heifer given a related MLV vaccine; Sequences of two respiratory isolates perfectly matched mutations characterizing RLB106 strain, a temperature sensitive mutant used in intranasal and parenteral vaccines. The last three respiratory strains clearly appeared related to a group of MLV vaccines. Previously the MLV vaccines were grouped into four groups based on SNPs patterns. In contrast with above-mentioned isolates that closely matched SNP patterns of their respective MLV vaccine virus, these 3 strains both lacked some and possessed a number of additional mutations compared to a group of MLV vaccine viral genome. Finding BoHV-1.2b in respiratory cases indicates focus should be given BoHV-1.2b as an emerging virus or a virus not recognized nor fully characterized in BRD. PMID:25454086

  8. Japanese Encephalitis Vaccines

    PubMed Central

    McArthur, Monica A.; Holbrook, Michael R.

    2012-01-01

    Japanese encephalitis (JE) is a significant human health concern in Asia, Indonesia and parts of Australia with more than 3 billion people potentially at risk of infection with Japanese encephalitis virus (JEV), the causative agent of JE. Given the risk to human health and the theoretical potential for JEV use as a bioweapon, the development of safe and effective vaccines to prevent JEV infection is vital for preserving human health. The development of vaccines for JE began in the 1940s with formalin-inactivated mouse brain-derived vaccines. These vaccines have been shown to induce a protective immune response and to be very effective. Mouse brain-derived vaccines were still in use until May 2011 when the last lots of the BIKEN® JE-VAX® expired. Development of modern JE vaccines utilizes cell culture-derived viruses and improvements in manufacturing processes as well as removal of potential allergens or toxins have significantly improved vaccine safety. China has developed a live-attenuated vaccine that has proven to induce protective immunity following a single inoculation. In addition, a chimeric vaccine virus incorporating the prM and E structural proteins derived from the live-attenuated JE vaccine into the live-attenuated yellow fever 17D vaccine virus backbone is currently in clinical trials. In this article, we provide a summary of JE vaccine development and on-going clinical trials. We also discuss the potential risk of JEV as a bioweapon with a focus on virus sustainability if used as a weapon. PMID:23125946

  9. Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine?

    PubMed

    Evans, Jennifer S; Horton, Daniel L; Easton, Andrew J; Fooks, Anthony R; Banyard, Ashley C

    2012-12-14

    All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens. PMID:23084854

  10. Pharmacogenomic Testing for Neuropsychiatric Drugs: Current Status of Drug Labeling, Guidelines for Using Genetic Information, and Test Options

    PubMed Central

    Drozda, Katarzyna; Müller, Daniel J.; Bishop, Jeffrey R.

    2014-01-01

    Advancements in pharmacogenomics have introduced an increasing number of opportunities to bring personalized medicine into clinical practice. Understanding how and when to use this technology to help guide pharmacotherapy used to treat neuropsychiatric conditions remains a challenge for many clinicians. Currently, guidelines exist to assist clinicians in the use of genetic information for drug selection and/or dosing for the tricyclic antidepressants, carbamazepine, and phenytoin. Additional language in the product labeling suggests that genetic information may also be useful for assessing the starting and target doses, as well as drug interaction potential, for a number of other medications used to treat psychiatric and neurological conditions. In this review, we outline the current status of pharmacogenomic testing for neuropsychiatric drugs as it pertains to information contained in drug labeling, consensus guidelines, and test panels, as well as considerations related to obtaining tests for patients. PMID:24523097

  11. The Current Landscape of Genetic Testing in Cardiovascular Malformations: Opportunities and Challenges.

    PubMed

    Landis, Benjamin J; Ware, Stephanie M

    2016-01-01

    Human cardiovascular malformations (CVMs) frequently have a genetic contribution. Through the application of novel technologies, such as next-generation sequencing, DNA sequence variants associated with CVMs are being identified at a rapid pace. While clinicians are now able to offer testing with NGS gene panels or whole exome sequencing to any patient with a CVM, the interpretation of genetic variation remains problematic. Variable phenotypic expression, reduced penetrance, inconsistent phenotyping methods, and the lack of high-throughput functional testing of variants contribute to these challenges. This article elaborates critical issues that impact the decision to broadly implement clinical molecular genetic testing in CVMs. Major benefits of testing include establishing a genetic diagnosis, facilitating cost-effective screening of family members who may have subclinical disease, predicting recurrence risk in offsprings, enabling early diagnosis and anticipatory management of CV and non-CV disease phenotypes, predicting long-term outcomes, and facilitating the development of novel therapies aimed at disease improvement or prevention. Limitations include financial cost, psychosocial cost, and ambiguity of interpretation of results. Multiplex families and patients with syndromic features are two groups where disease causation could potentially be firmly established. However, these account for the minority of the overall CVM population, and there is increasing recognition that genotypes previously associated with syndromes also exist in patients who lack non-CV findings. In all circumstances, ongoing dialog between cardiologists and clinical geneticists will be needed to accurately interpret genetic testing and improve these patients' health. This may be most effectively implemented by the creation and support of CV genetics services at centers committed to pursuing testing for patients. PMID:27504451

  12. The Current Landscape of Genetic Testing in Cardiovascular Malformations: Opportunities and Challenges

    PubMed Central

    Landis, Benjamin J.; Ware, Stephanie M.

    2016-01-01

    Human cardiovascular malformations (CVMs) frequently have a genetic contribution. Through the application of novel technologies, such as next-generation sequencing, DNA sequence variants associated with CVMs are being identified at a rapid pace. While clinicians are now able to offer testing with NGS gene panels or whole exome sequencing to any patient with a CVM, the interpretation of genetic variation remains problematic. Variable phenotypic expression, reduced penetrance, inconsistent phenotyping methods, and the lack of high-throughput functional testing of variants contribute to these challenges. This article elaborates critical issues that impact the decision to broadly implement clinical molecular genetic testing in CVMs. Major benefits of testing include establishing a genetic diagnosis, facilitating cost-effective screening of family members who may have subclinical disease, predicting recurrence risk in offsprings, enabling early diagnosis and anticipatory management of CV and non-CV disease phenotypes, predicting long-term outcomes, and facilitating the development of novel therapies aimed at disease improvement or prevention. Limitations include financial cost, psychosocial cost, and ambiguity of interpretation of results. Multiplex families and patients with syndromic features are two groups where disease causation could potentially be firmly established. However, these account for the minority of the overall CVM population, and there is increasing recognition that genotypes previously associated with syndromes also exist in patients who lack non-CV findings. In all circumstances, ongoing dialog between cardiologists and clinical geneticists will be needed to accurately interpret genetic testing and improve these patients’ health. This may be most effectively implemented by the creation and support of CV genetics services at centers committed to pursuing testing for patients. PMID:27504451

  13. Vaccination against helminth parasite infections.

    PubMed

    Hewitson, James P; Maizels, Rick M

    2014-04-01

    Helminth parasites infect over one fourth of the human population and are highly prevalent in livestock worldwide. In model systems, parasites are strongly immunomodulatory, but the immune system can be driven to expel them by prior vaccination. However, no vaccines are currently available for human use. Recent advances in vaccination with recombinant helminth antigens have been successful against cestode infections of livestock and new vaccines are being tested against nematode parasites of animals. Numerous vaccine antigens are being defined for a wide range of helminth parasite species, but greater understanding is needed to define the mechanisms of vaccine-induced immunity, to lay a rational platform for new vaccines and their optimal design. With human trials underway for hookworm and schistosomiasis vaccines, a greater integration between veterinary and human studies will highlight the common molecular and mechanistic pathways, and accelerate progress towards reducing the global health burden of helminth infection. PMID:24606541

  14. Human papillomavirus vaccine trials and tribulations: Vaccine efficacy.

    PubMed

    Handler, Nancy S; Handler, Marc Z; Majewski, Slawomir; Schwartz, Robert A

    2015-11-01

    As of December 2014, there were 3 approved vaccines for human papillomavirus (HPV): bivalent Cervarix (GlaxoSmithKline, New York, NY), quadrivalent Gardasil (Merck and Co, Kenilworth, NJ), and 9-valent Gardasil-9 (Merck and Co). The average cost per dose is $120, with a recommended 3-dose course. The quadrivalent vaccine is the most widely administered worldwide. As with the bivalent and 9-valent vaccines, the vaccine is considered safe, although concerns have been raised. In addition to immunization against the targeted HPV types, there is evidence that there is cross protection against other types of HPV. This continuing medical education review evaluates the differences in vaccines that are currently on the market; part II focuses on the cost-effectiveness of vaccination, the HPV vaccination programs currently instituted around the globe, efficacy, and safety. PMID:26475535

  15. Current progress on genetic interactions of rice with rice blast and sheath blight fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Analysis of genetic interactions between rice and its pathogenic fungi Magnaporthe oryzae and Rhizoctonia solani should lead to a better understanding of molecular mechanisms of host resistance, and the improvement of strategies to manage rice blast and sheath blight diseases. Presently dozens of ri...

  16. The genetics of Charcot–Marie–Tooth disease: current trends and future implications for diagnosis and management

    PubMed Central

    Hoyle, J Chad; Isfort, Michael C; Roggenbuck, Jennifer; Arnold, W David

    2015-01-01

    Charcot–Marie–Tooth (CMT) disease is the most common hereditary polyneuropathy and is classically associated with an insidious onset of distal predominant motor and sensory loss, muscle wasting, and pes cavus. Other forms of hereditary neuropathy, including sensory predominant or motor predominant forms, are sometimes included in the general classification of CMT, but for the purpose of this review, we will focus primarily on the forms associated with both sensory and motor deficits. CMT has a great deal of genetic heterogeneity, leading to diagnostic considerations that are still rapidly evolving for this disorder. Clinical features, inheritance pattern, gene mutation frequencies, and electrodiagnostic features all are helpful in formulating targeted testing algorithms in practical clinical settings, but these still have shortcomings. Next-generation sequencing (NGS), combined with multigene testing panels, is increasing the sensitivity and efficiency of genetic testing and is quickly overtaking targeted testing strategies. Currently, multigene panel testing and NGS can be considered first-line in many circumstances, although obtaining initial targeted testing for the PMP22 duplication in CMT patients with demyelinating conduction velocities is still a reasonable strategy. As technology improves and cost continues to fall, targeted testing will be completely replaced by multigene NGS panels that can detect the full spectrum of CMT mutations. Nevertheless, clinical acumen is still necessary given the variants of uncertain significance encountered with NGS. Despite the current limitations, the genetic diagnosis of CMT is critical for accurate prognostication, genetic counseling, and in the future, specific targeted therapies. Although whole exome and whole genome sequencing strategies have the power to further elucidate the genetics of CMT, continued technological advances are needed. PMID:26527893

  17. Future of Polio Vaccines

    PubMed Central

    2009-01-01

    Summary Over the past half-century, global use of highly effective vaccines against poliomyelitis brought this disease to the brink of elimination. Mounting evidence argues that a high level of population immunity must be maintained to preserve a polio-free status of the entire world after wild poliovirus circulation is stopped. Shifting factors in the risk-benefit-cost equation favor the creation of new poliovirus vaccines to be used in the foreseeable future. Genetically stable attenuated virus strains could be developed for an improved oral poliovirus vaccine, but proving their safety and efficacy would be impractical because of the enormous size of the clinical trials required. New versions of inactivated poliovirus vaccine (IPV) that could be used globally should be developed. An improved IPV must be efficacious, inexpensive, safe to manufacture, and easy to administer. Combination products containing IPV along with other protective antigens should become part of routine childhood immunizations around the world. PMID:19545205

  18. Vaccines, viruses, and voodoo.

    PubMed

    Borchers, Andrea T; Keen, Carl L; Shoenfeld, Yehuda; Silva, Joseph; Gershwin, M Eric

    2002-01-01

    Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease. PMID:12530114

  19. Genetic transformation of novel isolates of chicken Lactobacillus bearing probiotic features for expression of heterologous proteins: a tool to develop live oral vaccines

    PubMed Central

    Mota, Rodrigo M; Moreira, João Luiz S; Souza, Marcelo R; Fátima Horta, M; Teixeira, Santuza MR; Neumann, Elisabeth; Nicoli, Jacques R; Nunes, Álvaro C

    2006-01-01

    Background The use of lactic acid bacteria as vehicles to delivery antigens to immunize animals is a promising issue. When genetically modified, these bacteria can induce a specific local and systemic immune response against selected pathogens. Gastric acid and bile salts tolerance, production of antagonistic substances against pathogenic microorganisms, and adhesive ability to gut epithelium are other important characteristics that make these bacteria useful for oral immunization. Results Bacteria isolated on de Man, Rogosa and Sharpe medium (MRS) from different gastrointestinal portions of broiler chicks were evaluated for their resistance to artificial gastric acid and bile salts, production of hydrogen peroxide, and cell surface hydrophobicity. Thirty-eight isolates were first typed at species level by PCR amplification of 16S-23S rRNA intergenic spacers using universal primers that anneal within 16S and 23S genes, followed by restriction digestion analyses of PCR amplicons (PCR-ARDRA). An expression cassette was assembled onto the pCR2.1-Topo vector by cloning the promoter, leader peptide, cell wall anchor and terminator sequences derived from the laminin binding S-layer protein gene of L. crispatus strain F5.7 (lbs gene). A sequence encoding the green fluorescent protein (GFP) was inserted as reporter gene, and an erythromycin resistance gene was added as selective marker. All constructs were able to express GFP in the cloning host E. coli XL1-Blue and different Lactobacillus strains as verified by FACS and laser scanning confocal microscopy. Conclusion Lactobacillus isolated from gastrointestinal tract of broiler chickens and selected for probiotic characteristics can be genetically modified by introducing an expression cassette into the lbs locus. The transformed bacteria expressed on its cell wall surface different fluorescent proteins used as reporters of promoter function. It is possible then that similar bacterial model expressing pathogen antigens can

  20. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  1. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  2. One health/veterinary links associated with TB vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: participants will understand the current status of veterinary tuberculosis (TB) vaccine research for cattle and wildlife and their potential applications for development of human TB vaccines. Vaccines are lacking for many chronic intracellular pathogens requiring cell-mediated immunity ...

  3. The dichotomy of pathogens and allergens in vaccination approaches.

    PubMed

    Baird, Fiona J; Lopata, Andreas L

    2014-01-01

    Traditional prophylactic vaccination to prevent illness is the primary objective of many research activities worldwide. The golden age of vaccination began with an approach called variolation in ancient China and the evolution of vaccines still continues today with modern developments such as the production of Gardasil(TM) against HPV and cervical cancer. The historical aspect of how different forms of vaccination have changed the face of medicine and communities is important as it dictates our future approaches on both a local and global scale. From the eradication of smallpox to the use of an experimental vaccine to save a species, this review will explore these successes in infectious disease vaccination and also discuss a few significant failures which have hampered our efforts to eradicate certain diseases. The second part of the review will explore designing a prophylactic vaccine for the growing global health concern that is allergy. Allergies are an emerging global health burden. Of particular concern is the rise of food allergies in developed countries where 1 in 10 children is currently affected. The formation of an allergic response results from the recognition of a foreign component by our immune system that is usually encountered on a regular basis. This may be a dust-mite or a prawn but this inappropriate immune response can result in a life-time of food avoidance and lifestyle restrictions. These foreign components are very similar to antigens derived from infectious pathogens. The question arises: should the allergy community be focussing on protective measures rather than ongoing therapeutic interventions to deal with these chronic inflammatory conditions? We will explore the difficulties and benefits of prophylactic vaccination against various allergens by means of genetic technology that will dictate how vaccination against allergens could be utilized in the near future. PMID:25076945

  4. The dichotomy of pathogens and allergens in vaccination approaches

    PubMed Central

    Baird, Fiona J.; Lopata, Andreas L.

    2014-01-01

    Traditional prophylactic vaccination to prevent illness is the primary objective of many research activities worldwide. The golden age of vaccination began with an approach called variolation in ancient China and the evolution of vaccines still continues today with modern developments such as the production of GardasilTM against HPV and cervical cancer. The historical aspect of how different forms of vaccination have changed the face of medicine and communities is important as it dictates our future approaches on both a local and global scale. From the eradication of smallpox to the use of an experimental vaccine to save a species, this review will explore these successes in infectious disease vaccination and also discuss a few significant failures which have hampered our efforts to eradicate certain diseases. The second part of the review will explore designing a prophylactic vaccine for the growing global health concern that is allergy. Allergies are an emerging global health burden. Of particular concern is the rise of food allergies in developed countries where 1 in 10 children is currently affected. The formation of an allergic response results from the recognition of a foreign component by our immune system that is usually encountered on a regular basis. This may be a dust-mite or a prawn but this inappropriate immune response can result in a life-time of food avoidance and lifestyle restrictions. These foreign components are very similar to antigens derived from infectious pathogens. The question arises: should the allergy community be focussing on protective measures rather than ongoing therapeutic interventions to deal with these chronic inflammatory conditions? We will explore the difficulties and benefits of prophylactic vaccination against various allergens by means of genetic technology that will dictate how vaccination against allergens could be utilized in the near future. PMID:25076945

  5. Biological challenges to effective vaccines in the developing world

    PubMed Central

    Grassly, Nicholas C.; Kang, Gagandeep; Kampmann, Beate

    2015-01-01

    The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approaches are necessary to understand the heterogeneity in responses and to improve vaccine immunogenicity and efficacy. PMID:25964451

  6. Biological challenges to effective vaccines in the developing world.

    PubMed

    Grassly, Nicholas C; Kang, Gagandeep; Kampmann, Beate

    2015-06-19

    The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approaches are necessary to understand the heterogeneity in responses and to improve vaccine immunogenicity and efficacy. PMID:25964451

  7. Developing new smallpox vaccines.

    PubMed Central

    Rosenthal, S. R.; Merchlinsky, M.; Kleppinger, C.; Goldenthal, K. L.

    2001-01-01

    New stockpiles of smallpox vaccine are required as a contingency for protecting civilian and military personnel against deliberate dissemination of smallpox virus by terrorists or unfriendly governments. The smallpox vaccine in the current stockpile consists of a live animal poxvirus (Vaccinia virus [VACV]) that was grown on the skin of calves. Because of potential issues with controlling this earlier manufacturing process, which included scraping VACV lesions from calfskin, new vaccines are being developed and manufactured by using viral propagation on well-characterized cell substrates. We describe, from a regulatory perspective, the various strains of VACV, the adverse events associated with calf lymph-propagated smallpox vaccine, the issues regarding selection and use of cell substrates for vaccine production, and the issues involved in demonstrating evidence of safety and efficacy. PMID:11747717

  8. Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges

    PubMed Central

    Wilke, Russell A.; Lin, Debbie W.; Roden, Dan M.; Watkins, Paul B.; Flockhart, David; Zineh, Issam; Giacomini, Kathleen M.; Krauss, Ronald M.

    2009-01-01

    Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug's pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing genotypes may improve patient management through the prospective selection of appropriate candidates. Here we discuss three specific SADRs with an emphasis on genetic risk factors. These SADRs, selected based on wide-sweeping clinical interest, are drug-induced liver injury, statin-induced myotoxicity and drug-induced long QT and torsades de pointes. Key challenges for the discovery of predictive risk alleles for these SADRs are also considered. PMID:17971785

  9. The genetics of multiple sclerosis: review of current and emerging candidates.

    PubMed

    Muñoz-Culla, Maider; Irizar, Haritz; Otaegui, David

    2013-01-01

    Multiple sclerosis (MS) is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. PMID:24019748

  10. The genetics of multiple sclerosis: review of current and emerging candidates

    PubMed Central

    Muñoz-Culla, Maider; Irizar, Haritz; Otaegui, David

    2013-01-01

    Multiple sclerosis (MS) is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. PMID:24019748

  11. Optimal vaccination choice, vaccination games, and rati