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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. 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

  17. [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

  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. 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

  13. 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

  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. 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

  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. 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

  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 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

  18. 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

  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. 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

  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. 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

  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

    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

  10. 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

  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. 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

  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. 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

  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. 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

  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. 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.

  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. 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

  10. 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

  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. 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

  19. 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

  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. 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

  3. 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

  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. 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

  6. 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

  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. 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

  12. 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

  13. 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

  14. 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

  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. 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

  18. 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

  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 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...

  4. 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

  5. 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

  6. 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

  7. 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

  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