Sample records for vaccines biological products

  1. 78 FR 60884 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ...FDA-2013-N-0001] Vaccines and Related Biological Products Advisory Committee; Notice...Name of Committee: Vaccines and Related Biological Products Advisory Committee. General...would constitute a clearly unwarranted invasion of personal privacy (5 U.S.C....

  2. 78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ...FDA-2013-N-0001] Vaccines and Related Biological Products Advisory Committee; Notice...Name of Committee: Vaccines and Related Biological Products Advisory Committee. General...would constitute a clearly unwarranted invasion of personal privacy (5 U.S.C....

  3. 76 FR 55397 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ...FDA-2011-N-0002] Vaccines and Related Biological Products Advisory Committee; Notice...Name of Committee: Vaccines and Related Biological Products Advisory Committee. General...would constitute a clearly unwarranted invasion of personal privacy (5 U.S.C....

  4. 76 FR 44016 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ...FDA-2011-N-0002] Vaccines and Related Biological Products Advisory Committee; Notice...Name of Committee: Vaccines and Related Biological Products Advisory Committee. General...would constitute a clearly unwarranted invasion of personal privacy (5 U.S.C....

  5. 77 FR 3780 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ...FDA-2012-N-0001] Vaccines and Related Biological Products Advisory Committee; Notice...Name of Committee: Vaccines and Related Biological Products Advisory Committee. General...would constitute a clearly unwarranted invasion of personal privacy (5 U.S.C....

  6. 76 FR 52668 - Vaccines and Related Biological Products Advisory Committee; Amendment of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ...FDA-2011-N-0002] Vaccines and Related Biological Products Advisory Committee...of the Vaccines and Related Biological Products Advisory Committee...of the Vaccines and Related Biological Products Advisory Committee...constitute a clearly unwarranted invasion of personal privacy (5...

  7. Vaccine Production

    Microsoft Academic Search

    Jack Melling

    \\u000a The biotechnology revolution which began in the 1970s with the advent of genetic engineering, coupled with major developments\\u000a in fermentation and downstream processing technology, has had major impacts on research, development and production of vaccines.\\u000a In the case of vaccine production, the effect of recombinant DNA techniques has been to make vaccines available against agents\\u000a where previously production and isolation

  8. Evaluation of Mycoplasma inactivation during production of biologics: egg-based viral vaccines as a model.

    PubMed

    David, Selwyn A Wilson; Volokhov, Dmitriy V; Ye, Zhiping; Chizhikov, Vladimir

    2010-05-01

    Although mycoplasmas are generally considered to be harmless commensals, some mycoplasma species are able to cause infections in pediatric, geriatric, or immunocompromised patients. Thus, accidental contamination of biologics with mycoplasmas represents a potential risk for the health of individuals who receive cell-derived biological and pharmaceutical products. To assess the efficiency of inactivation of mycoplasmas by the agents used in the manufacture of egg-derived influenza vaccines, we carried out a series of experiments aimed at monitoring the viability of mycoplasmas spiked into both chicken allantoic fluid and protein-rich microbiological media and then treated with beta-propiolactone, formalin, cetyltrimethylammonium bromide, Triton X-100, and sodium deoxycholate, which are agents that are commonly used for virus inactivation and disruption of viral particles during influenza vaccine production. Twenty-two mycoplasma species (with one to four strains of each species) were exposed to these inactivating agents at different concentrations. The most efficient inactivation of the mycoplasmas evaluated was observed with either 0.5% Triton X-100 or 0.5% sodium deoxycholate. Cetyltrimethylammonium bromide at concentrations of >or=0.08% was also able to rapidly inactivate (in less than 30 min) all mycoplasmas tested. In contrast, negligible reductions in mycoplasma titers were observed with 0.0125 to 0.025% formaldehyde. However, increasing the concentration of formaldehyde to 0.1 to 0.2% improved the mycoplasmacidal effect. Incubation of mycoplasmas with 0.1% beta-propiolactone for 1 to 24 h had a marked mycoplasmacidal effect. A comparison of the mycoplasma inactivation profiles showed that strains of selected species (Mycoplasma synoviae, Mycoplasma gallisepticum, Mycoplasma orale, Mycoplasma pneumoniae, and Acholeplasma laidlawii) represent a set of strains that can be utilized to validate the effectiveness of mycoplasma clearance obtained by inactivation and viral purification processes used for the manufacture of an inactivated egg-based vaccine. PMID:20228111

  9. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ...demonstration of effectiveness of meningococcal serogroups A, C, Y, and W-135 conjugate vaccines administered to children less...approaches to licensure of meningococcal serogroup B vaccines. FDA intends to make...

  10. 77 FR 63839 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ...the safety and immunogenicity of an Influenza A (H5N1) Virus Monovalent Vaccine manufactured by GlaxoSmithKline. On...and make recommendations on the safety and efficacy of a Hepatitis B Vaccine manufactured by Dynavax. FDA intends to...

  11. Rapid production of synthetic influenza vaccines.

    PubMed

    Dormitzer, Philip R

    2015-01-01

    The strain composition of influenza vaccines must be changed regularly to track influenza virus antigenic evolution. During outbreaks with pandemic potential, strain changes are urgent. The systems for accomplishing vaccine strain changes have required the shipment of viruses and other biological materials around the globe, with delays in vaccine availability, and have used legacy techniques of egg-based virus cultivation, resulting in vaccine mismatches. In collaboration with Synthetic Genomics Vaccines Inc. and the US Biomedical Advanced Research and Development Authority, Novartis has developed a synthetic approach to influenza vaccine virus generation. Synthetic influenza vaccine viruses and mammalian cell culture technology promise influenza vaccines that match circulating influenza strains more closely and are delivered in greater quantities, more rapidly than vaccines produced by conventional technologies. These new technologies could yield an improved influenza vaccine response system in which viral sequence data from many sources are posted on the Internet, are downloaded by vaccine manufacturers, and are used to rescue multiple, attenuated vaccine viruses directly on high yielding backbones. Elements of this system were deployed in the response to the 2013 H7N9 influenza outbreak in China. The result was the production, clinical testing, and stockpiling of an H7N9 vaccine before the second wave of the outbreak struck at the end of 2013. Future directions in synthetic influenza vaccine technology include the automation of influenza virus rescue from sequence data and the merger of synthetic and self-amplifying mRNA vaccine technologies. The result could be a more robust and effective influenza vaccine system. PMID:24996863

  12. Vaccines against biologic agents: uses and developments.

    PubMed

    Ales, Noel C; Katial, Rohit K

    2004-03-01

    Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades. This delay allowed the continued development of chemical and biologic agents. Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents. Ideally,these diseases would be prevented from ever developing into systemic illnesses. In the past, vaccination has been a successful means of eradicating disease. Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease. Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines. Furthermore, some human studies would not be safe or ethical. Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination. It is therefore naive to believe that vaccines would be the ultimate protection from these agents. In addition to vaccine development, there must be concurrent investigations into disease management and treatment. Even in instances in which vaccination is known to be an effective means of disease protection. biologic agents may be presented in a manner that renders vaccines ineffective. Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance. Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high concentrations of organisms may overcome vaccine protection. Finally,exposure may not be immediately noted until it is too late to vaccinate, as was the case with anthrax. Even in a case, such as smallpox, in which postexposure vaccination is possible, patients will still develop disease, and the health care system may be overwhelmed. The United States government has been defensively planning and researching the use of vaccines and chemoprophylaxis against any potential biologic agents since at least 1953, and resources are still lacking. There are inadequate stockpiles of vaccine to protect the entire population. The pharmaceutical industry also lacks a means of mass producing vaccines ina short timeframe. There is no policy in place for the use of vaccines that are yet unlicensed and experimental but may be the only therapy in the event ofa terrorist attack. Investigations into these solutions have been instituted only after the September 11, 2001, attacks heightened the awareness of terrorism. Although vaccination is an effective means of prophylaxis and a means of terminating epidemics or treating active disease, there is also resistance from the general public. In some instances there is a lack of acceptance of vaccines, or the risk of side effects is too great. In other cases, a questionable benefit does not justify the expense of mass vaccination. Because of this uncertainty, mass vaccination is deemed an impractical solution to the threat of bioterrorism. Extending vaccination with most vaccines to include all members of society who may be first responders in the event of an attack should be considered. In all instances, the benefit-to-risk must be weighed ratio when deciding how and when to offer preemptive prophylaxis to protect society from a real but unknown threat. PMID:15062232

  13. Food and Drug Administration (FDA) Vaccines, Blood & Biologics

    NSDL National Science Digital Library

    On this site, visitors can learn about the regulations and standards for Vaccines, Blood & Biologics. The site is divided up into a number of broad areas, including Allergenics, Cellular and Gene Therapy Products, Tissue and TIssue Products, and Xenotransplantation. The right side of the page also presents handy current issues, including recalls and alerts, and approvals and clearances.

  14. Biological challenges to effective vaccines in the developing world.

    PubMed

    Grassly, Nicholas C; Kang, Gagandeep; Kampmann, Beate

    2015-06-19

    The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approaches are necessary to understand the heterogeneity in responses and to improve vaccine immunogenicity and efficacy. PMID:25964451

  15. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans

    Microsoft Academic Search

    Troy D Querec; Rama S Akondy; Eva K Lee; Weiping Cao; Helder I Nakaya; Dirk Teuwen; Ali Pirani; Kim Gernert; Jiusheng Deng; Bruz Marzolf; Kathleen Kennedy; Haiyan Wu; Soumaya Bennouna; Herold Oluoch; Joseph Miller; Ricardo Z Vencio; Mark Mulligan; Alan Aderem; Rafi Ahmed; Bali Pulendran

    2008-01-01

    A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and

  16. Immunogenomics and systems biology of vaccines

    PubMed Central

    Buonaguro, Luigi; Pulendran, Bali

    2011-01-01

    Summary Vaccines represent a potent tool to prevent or contain infectious diseases with high morbidity or mortality. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the effective elicitation of protective immune responses by vaccines. Recent research suggests that this represents the cooperative action of the innate and adaptive immune systems. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules, whose list is constantly updated to fill the several empty spaces of this puzzle. The recent development of new technologies and computational tools permits the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review the role of the innate immunity in the host response to vaccine antigens and the potential of systems biology in providing relevant and novel insights in the mechanisms of action of vaccines to improve their design and effectiveness. PMID:21198673

  17. The Optimal Composition of Influenza Vaccines Subject to Random Production Yields

    E-print Network

    1 The Optimal Composition of Influenza Vaccines Subject to Random Production Yields Soo-Haeng Cho1@anderson.ucla.edu December 30, 2007 Abstract The Vaccine and Related Biologic Products Advisory Committee meets at least once a year to decide the composition of the influenza vaccine in the U.S. Past evidence suggests

  18. Vaccine production, distribution, access and uptake

    PubMed Central

    Smith, Jon; Lipsitch, Marc; Almond, Jeffrey W.

    2011-01-01

    Making human vaccines available on a global scale requires the use of complex production methods, meticulous quality control and reliable distribution channels that ensure the products are potent and effective at their point of use. The technologies involved in manufacturing different types of vaccines may strongly influence vaccine cost, ease of industrial scale-up, stability and ultimately world-wide availability. Manufacturing complexity is compounded by the need for different formulations for different countries and age groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, ensuring optimal access and uptake also requires strong partnerships between private manufacturers, regulatory authorities and national and international public health services. For vaccines whose supplies are limited, either due to rapidly emerging diseases or longer-term mismatch of supply and demand, prioritizing target groups can increase vaccine impact. Focusing on influenza vaccines as an example that well illustrates many of the relevant points, this article considers current production, distribution, access and other factors that ultimately impact on vaccine uptake and population-level effectiveness. PMID:21664680

  19. Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

    PubMed

    Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

    2015-02-01

    Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination. PMID:25566800

  20. Systems Biology of Seasonal Influenza Vaccination in Humans

    PubMed Central

    Nakaya, Helder I; Wrammert, Jens; Lee, Eva K; Racioppi, Luigi; Marie-Kunze, Stephanie; Haining, W. Nicholas; Means, Anthony R; Kasturi, Sudhir P; Khan, Nooruddin; Li, Gui-Mei; McCausland, Megan; Kanchan, Vibhu; Kokko, Kenneth E; Li, Shuzhao; Elbein, Rivka; Mehta, Aneesh K; Aderem, Alan; Subbarao, Kanta; Ahmed, Rafi; Pulendran, Bali

    2011-01-01

    We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV ?/? mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines. PMID:21743478

  1. Cattle Vaccines 

    E-print Network

    Faries Jr., Floron C.

    2005-11-11

    Vaccines deliver antigens that stimulate the body's production of antibodies in response to disease. Cattle can be vaccinated with noninfectious or infectious vaccines. The types of vaccine products, proper handling of vaccines, and vaccination...

  2. Journal of Theoretical Biology 224 (2003) 269275 Estimation of effective vaccination rate

    E-print Network

    Maini, Philip K.

    2003-01-01

    Journal of Theoretical Biology 224 (2003) 269­275 Estimation of effective vaccination rate and secondary failures. To evaluate efficiency of vaccination we introduce the idea of effective vaccination time (Cullen and Walker, 1997). This leads to the question of how effective is the vaccination

  3. FDA 101: Regulating Biological Products

    MedlinePLUS

    ... mail Consumer Updates RSS Feed FDA 101: Regulating Biological Products Search the Consumer Updates Section Consumer Update ... friendly PDF (196 KB) On this page: What biological products does FDA regulate? How do biologics differ ...

  4. 60 FR 21823 - Drug Export; VAQTASUPTM Hepatitis A Vaccine, Purified Inactivated

    Federal Register 2010, 2011, 2012, 2013, 2014

    1995-05-03

    ...95N-0108] Drug Export; VAQTA TM Hepatitis A Vaccine, Purified Inactivated AGENCY...bulk human biological product VAQTA TM Hepatitis A Vaccine, Purified Inactivated to the...bulk human biological product VAQTA TM Hepatitis A Vaccine, Purified Inactivated,...

  5. [Optimization of the pertussis vaccine production process].

    PubMed

    Germán Santiago, J; Zamora, N; de la Rosa, E; Alba Carrión, C; Padrón, P; Hernández, M; Betancourt, M; Moretti, N

    1995-01-01

    The production of Pertussis Vaccine was reevaluated at the Instituto Nacional de Higiene "Rafael Rangel" in order to optimise it in terms of vaccine yield, potency, specific toxicity and efficiency (cost per doses). Four different processes, using two culture media (Cohen-Wheeler and Fermentación Glutamato Prolina-1) and two types of bioreactors (25 L Fermentador Caracas and a 450 L industrial fermentor) were compared. Runs were started from freeze-dried strains (134 or 509) and continued until the obtention of the maximal yield. It was found that the combination Fermentación Glutamato Prolina-1/industrial fermentor, shortened the process to 40 hours while consistently yielding a vaccine of higher potency (7.91 +/- 2.56 IU/human dose) and lower specific toxicity in a mice bioassay. In addition, the physical aspect of the preparation was rather homogeneous and free of dark aggregates. Most importantly, the biomass yield more than doubled those of the Fermentador Caracas using the two different media and that in the industrial fermentor with the Cohen-Wheeler medium. Therefore, the cost per doses was substantially decreased. PMID:9279028

  6. The biology of avian Eimeria with an emphasis on their control by vaccination.

    PubMed

    Shirley, Martin W; Smith, Adrian L; Tomley, Fiona M

    2005-01-01

    Studies on the biology of the avian species of Eimeria are currently benefiting from the availability of a comprehensive sequence for the nuclear genome of Eimeria tenella. Allied to some recent advances in transgenic technologies and genetic approaches to identify protective antigens, some elements are now being assembled that should be helpful for the development of a new generation of vaccines. In the meantime, control of avian coccidiosis by vaccination represents a major success in the fight against infections caused by parasitic protozoa. Live vaccines that comprise defined populations of oocysts are used routinely and this form of vaccination is based upon the long-established fact that chickens infected with coccidial parasites rapidly develop protective immunity against challenge infections with the same species. Populations of wild-type Eimeria parasites were the basis of the first live vaccines introduced around 50 years ago and the more recent introduction of safer, live-attenuated, vaccines has had a significant impact on coccidiosis control in many areas of the world. In Europe the introduction of vaccination has coincided with declining drug efficacy (on account of drug resistance) and increasing concerns by consumers about the inclusion of in-feed medication and prospects for drug residues in meat. The use of attenuated vaccines throughout the world has also stimulated a greater interest in the vaccines that comprise wild-type parasites and, during the past 3 years worldwide, around 3x10(9) doses of each type of vaccine have been used. The need for only small numbers of live parasites to induce effective protective immunity and the recognition that Eimeria spp. are generally very potent immunogens has stimulated efforts to develop other types of vaccines. None has succeeded except for the licensing, within several countries in 2002, of a vaccine (CoxAbic vaccine; Abic, Israel) that protects via the maternal transfer of immunoglobulin to the young chick. Building on the success of viral vaccines that are delivered via the embryonating egg, an in ovo coccidiosis vaccine (Inovocox, Embrex Inc.) is currently in development. Following successful field trials in 2001, the product will be ready for Food and Drug Administration approval in 2005 and a manufacturing plant will begin production for sale in late 2005. Limited progress has been achieved towards the development of subunit or recombinant vaccines. No products are available and studies to identify potential antigens remain compromised by an absence of effective in vitro assays that correlate with the induction of protective immunity in the host. To date, only a relatively small portfolio of molecules has been evaluated for an ability to induce protection in vivo. Although Eimeria are effective immunogens, it is probable that to date none of the antigens that induce potent protective immune responses during the course of natural infection has been isolated. PMID:16230106

  7. Avipoxviruses: infection biology and their use as vaccine vectors

    PubMed Central

    2011-01-01

    Avipoxviruses (APVs) belong to the Chordopoxvirinae subfamily of the Poxviridae family. APVs are distributed worldwide and cause disease in domestic, pet and wild birds of many species. APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated. The virus species Fowlpox virus (FWPV) causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production) mortality can reach up to 50%. APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine. Abortive infection in mammalian cells (no production of progeny viruses) and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors. Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood. This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors. PMID:21291547

  8. 72 FR 4470 - Viruses, Serums, Toxins, and Analogous Products; Standard Requirements for Live Vaccines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2007-01-31

    We are proposing to amend the Virus-Serum-Toxin Act regulations for certain live bacterial and viral vaccines by removing the requirement to retest the Master Seeds for immunogenicity 3 years after the initial qualifying immunogenicity test. In addition, we are proposing to amend the requirement concerning mouse safety tests prescribed for a biological product recommended for animals other than......

  9. Production of a falcon herpesvirus vaccine.

    PubMed

    Wernery, U; Wernery, R; Kinne, J

    1999-09-01

    Ten common kestrels (Falco tinnunculus) were used for this falcon herpes vaccine experiment. Four kestrels were subcutaneously given 1 ml of an attenuated falcon herpesvirus that had originally been isolated from the liver of an American prairie falcon (Falco mexicanus). This virus was then passaged 100 times on chicken embryo fibroblast cells (CEF-cells). Another 4 kestrels were given subcutaneously an inactivated falcon herpesvirus vaccine derived from the same American field strain. This vaccine was concentrated, inactivated by heat and betapropiolactone and emulsified in complete Freund's adjuvans. Two further kestrels served as controls and were not vaccinated. Twenty-one days after vaccination, all 10 kestrels were challenged with passage 3 of the American falcon herpesvirus. The 2 control kestrels died 6 days after challenge and 3 of those given the inactivated herpes vaccine died 9 days after challenge, with typical lesions of herpesvirus inclusion body hepatitis. Before the vaccination experiment, all 10 kestrels were free of serum neutralising antibodies to the falcon herpesvirus. Twenty-one days after vaccination, all 4 kestrels vaccinated with the attenuated vaccine, and one vaccinated with the killed vaccine, had seroconverted, having shown no symptoms to the challenge with a low passage virulent American herpesvirus strain. Following the challenge their antibody titres to falcon herpesvirus increased. No herpesvirus was isolated from any of the cloacal swabs taken during this experiment, indicating that there is no danger for any other birds from the attenuated herpesvirus vaccine. This experiment clearly shows that an attenuated falcon herpesvirus vaccine can protect kestrels from fatal inclusion body hepatitis. PMID:10507183

  10. The Differential Impact of Coadministered Vaccines, Geographic Region, Vaccine Product and Other Covariates on Pneumococcal Conjugate Vaccine Immunogenicity

    PubMed Central

    2014-01-01

    Background: Antipneumococcal capsular polysaccharide antibody concentrations are used as predictors of vaccine efficacy against vaccine serotype (ST) pneumococcal disease among infants. While pneumococcal conjugate vaccines (PCV) are recommended globally, factors associated with optimal PCV immune response are not well described. We aimed to systematically assess local setting factors, beyond dosing schedule, which may affect PCV antibody levels. Methods: We conducted a literature review of PCV immunogenicity, abstracting data from published reports, unpublished sources, and conference abstracts from 1994 to 2010 (and ad hoc 2011 reports). Studies included in this analysis evaluated ? 2 primary doses of PCV before 6 months of age in non–high-risk populations, used 7-valent or higher PCV products (excluding Aventis-Pasteur and Merck products) and provided information on geometric mean concentration (GMC) for STs 1, 5, 6B, 14, 19F or 23F. Using random effects meta-regression, we assessed the impact of geographic region, coadministered vaccines and PCV product on postprimary GMC, adjusting for dosing schedule and ELISA laboratory method. Results: Of 12,980 citations reviewed, we identified 103 vaccine study arms for this analysis. Children in studies from Asia, Africa and Latin America had significantly higher GMC responses compared with those in studies from Europe and North America. Coadministration with acellular pertussis DTP compared with whole-cell DTP had no effect on PCV immunogenicity except for ST14, where GMCs were higher when coadministered with acellular pertussis DTP. Vaccine product, number of PCV doses, dosing interval, age at first dose and ELISA laboratory method also affected the GMC. Conclusions: PCV immunogenicity is associated with geographic region and vaccine product; however, the associations and magnitude varied by ST. Consideration of these factors is essential when comparing PCV immunogenicity results between groups and should be included in the evidence base when selecting optimal PCV vaccine schedules in specific settings. PMID:24336055

  11. Molecular farming: production of drugs and vaccines in higher plants

    Microsoft Academic Search

    Atsuhiko Shinmyo; Ko Kato

    2010-01-01

    On the basis of developments in plant biotechnology, drug and vaccine production by higher plants can be added to microbial and animal cell culture processes. When genes encoding drug or vaccine formation under a suitable promoter are introduced into plants, these useful compounds can be economically produced from CO2 and inorganic chemicals using sunlight. The merits and demerits of the

  12. Hairy roots as a vaccine production and delivery system.

    PubMed

    Skarjinskaia, Marina; Ruby, Karen; Araujo, Adriana; Taylor, Karina; Gopalasamy-Raju, Vengadesan; Musiychuk, Konstantin; Chichester, Jessica A; Palmer, Gene A; de la Rosa, Patricia; Mett, Vadim; Ugulava, Natalia; Streatfield, Stephen J; Yusibov, Vidadi

    2013-01-01

    Prevention of infectious diseases by vaccination is often limited because of the lack of safe, effective, and accessible vaccines. Traditional vaccines are expensive and require special conditions for storage, distribution, and administration. Plants have potential for large-scale production of a variety of inexpensive and highly effective recombinant proteins for biomedical and pharmaceutical applications, including subunit vaccines. There are several approaches for the production of vaccine antigens in plants, including transient expression systems based on Agrobacterium delivery of binary vectors or plant viral vectors, stable transgenic plants, and plant cell or tissue cultures. Axenic plant cultures maintained under defined physical and chemical conditions appear to be an attractive production platform when target proteins need to be synthesized in a fully controlled environment. Hairy root cultures meet the criteria for such a system. Hairy root cultures, generated from edible plants and producing target antigens, provide a potential approach for the development of vaccines for oral delivery. With this approach, there are no protein extraction and purification costs and the active biomolecule is protected by the plant cell wall during passage through the upper gastrointestinal tract. This allows for gradual release of antigen at mucosal surfaces in the gut. Lyophilized hairy root cultures expressing vaccine antigens can be stored at ambient temperature for extended periods of time, which should facilitate storage and distribution, ultimately allowing for large populations to be vaccinated. PMID:23649385

  13. Scientific challenges for the quality control and production of group C meningococcal conjugate vaccines.

    PubMed

    Jódar, Luis; Griffiths, Elwyn; Feavers, Ian

    2004-02-25

    Recommendations (formerly known as requirements) for meningococcal polysaccharide vaccines were adopted by the World Health Organisation (WHO) Expert Committee on Biological Standardisation in 1976 and amended in 1978 and 1981. In clinical studies, these vaccines have been shown to have efficacy of at least 90% and have proved to be highly effective in vaccination programmes. Nevertheless, their inability to elicit protective responses in young infants or to induce good immunological memory has prevented their implementation in national infant immunisation schedules. Following the successful introduction of the Haemophilus influenzae type b conjugate (Hib) vaccines, considerable progress has been made in the development of similar conjugate vaccines based on meningococcal group C capsular polysaccharide. Controlled clinical trials have demonstrated that they induce protective levels of antibodies to group C polysaccharide in all age groups and, as T-cell dependent antigens, induce immunological memory and affinity maturation of anti-capsular antibodies. Such vaccines have been shown to offer protective immunity following the introduction of group C conjugates in the UK. The World Health Organisation has produced recommendations for the production and control of these new vaccines. PMID:15161082

  14. A Synthetic Biology Approach for a Vaccine Platform against Known and Newly Emerging Serotypes of Bluetongue Virus

    PubMed Central

    Nunes, Sandro Filipe; Hamers, Claude; Ratinier, Maxime; Shaw, Andrew; Brunet, Sylvie; Hudelet, Pascal

    2014-01-01

    ABSTRACT Bluetongue is one of the major infectious diseases of ruminants and is caused by bluetongue virus (BTV), an arbovirus existing in nature in at least 26 distinct serotypes. Here, we describe the development of a vaccine platform for BTV. The advent of synthetic biology approaches and the development of reverse genetics systems has allowed the rapid and reliable design and production of pathogen genomes which can be subsequently manipulated for vaccine production. We describe BTV vaccines based on “synthetic” viruses in which the outer core proteins of different BTV serotypes are incorporated into a common tissue-culture-adapted backbone. As a means of validation for this approach, we selected two BTV-8 synthetic reassortants and demonstrated their ability to protect sheep against virulent BTV-8 challenge. In addition to further highlight the possibilities of genome manipulation for vaccine production, we also designed and rescued a synthetic BTV chimera containing a VP2 protein, including regions derived from both BTV-1 and BTV-8. Interestingly, while the parental viruses were neutralized only by homologous antisera, the chimeric proteins could be neutralized by both BTV-1 and BTV-8 antisera. These data suggest that neutralizing epitopes are present in different areas of the BTV VP2 and likely “bivalent” strains eliciting neutralizing antibodies for multiple strains can be obtained. IMPORTANCE Overall, this vaccine platform can significantly reduce the time taken from the identification of new BTV strains to the development and production of new vaccines, since the viral genomes of these viruses can be entirely synthesized in vitro. In addition, these vaccines can be brought quickly into the market because they alter the approach, but not the final product, of existing commercial products. PMID:25142610

  15. Product review on the JE vaccine IXIARO.

    PubMed

    Firbas, Christa; Jilma, Bernd

    2015-01-01

    Japanese encephalitis virus, as the most important vaccine-preventable cause of viral encephalitis in Asia, is estimated to cause over 68,000 clinical cases yearly. In endemic areas, most Japanese encephalitis infections occur in children younger than 10 y and clinical manifestation of this disease is critical, because there is no effective treatment available. As JEV infections are regarded as one of the most serious viral causes of encephalitis and mass immunization programmes are generally recommended for residents in endemic areas, a safe and effective JEV vaccine was needed to protect them as well as others at risk. Due to the safety concerns with the mouse brain derived vaccine, second generation vaccines against JE produced in cell culture like Vero cells were developed. IXIARO® is a purified, inactivated aluminum-adjuvanted JE vaccine, based on the SA14-14-2 virus strain, and is available in North America, Europe, Canada, Switzerland, Singapore, Hong Kong and Israel as well as in Australia & New Zealand (as JESPECT®).The safety, tolerability and immunogenicity profile of IXIARO® is well established through a number of clinical studies comparing IXIARO® with placebo as well as mouse brain derived vaccine. Recent data show that the global incidence of JE remains substantial, especially young children in endemic areas are most susceptible. As vaccination is the most feasible, reliable and cost effective tool for JE control, IXIARO® with confirmed excellent safety profile is highly recommendable, in particular for vaccination of children at risk. The European Commission as well as the FDA approved the extension of indication of IXIARO® to the pediatric segment (2 months of age and older) based on these data. PMID:25621812

  16. Current status of production and market of human vaccine products in Korea

    PubMed Central

    Kim, So Youn; Cho, Jahyang; Cha, Sung-Ho

    2013-01-01

    Purpose The goal of this study was to build basic information related to the production and market of human vaccine products in Korea, which can be an important indicator to provide basic data in practical use. Materials and Methods Statistical data were obtained from the Bank of Korea, Korea Health Industry Development Institute, Korea Pharmaceutical Traders Association, and Korea Pharmaceutical Manufacturers Association. Results Vaccines are the 10th ranked drugs in the classification of whole complete preparated drugs. The production output of vaccines in Korea was 392.2 billion KRW in 2011, comprising 2.83% of complete preparated drug production output (13 trillion 880.8 billion KRW) and 2.54% of medical-pharmaceutical product output (15 trillion 440.3 billion KRW). The market scale of vaccines in Korea was 710 billion KRW in 2011, with an annual average growth rate of 11% in the past 6 years, comprising 2% of vaccine market in the world. There was also a significant increase in essential vaccines and other preventive vaccines in a global scale. Conclusion Vaccines have the potential of becoming an emerging attractive industry. Based on the current analysis about the production of vaccine products and market scale, further development of the vaccine industry is expected in Korea. PMID:23858403

  17. IRRIGATION FOR VACCINE PRODUCTION IN PHARMACEUTICAL TOBACCO

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biotechnology companies in North America and Europe have engineered plants to produce recombinant proteins for therapeutic drugs and vaccines. Chlorogen, Inc. located in St. Louis, Missouri, inserted the protective antigen (PA) gene from Bacillus anthracis into tobacco (Nicotiana tabacum cv LAMD 60...

  18. Production of EV71 vaccine candidates.

    PubMed

    Chong, Pele; Hsieh, Shih-Yang; Liu, Chia-Chyi; Chou, Ai-Hsiang; Chang, Jui-Yuan; Wu, Suh-Chin; Liu, Shih-Jen; Chow, Yen-Hung; Su, Ih-Jen; Klein, Michel

    2012-12-01

    Enterovirus 71 (EV71) is now recognized as an emerging neurotropic virus in Asia and with Coxsackie virus (CV) it is the other major causative agent of hand-foot-mouth diseases (HFMD). Effective medications and/or prophylactic vaccines against HFMD are urgently needed. From a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of different EV71 vaccine candidates that have been produced and evaluated in animal models. Epitope-based synthetic peptide vaccine candidates containing residues 211-225 of VP1 formulated with Freund's adjuvant (CFA/IFA) elicited low EV71 virus neutralizing antibody responses, but were protective in the suckling mouse challenge model. Among recombinant EV71 subunits (rVP1, rVP2 and rVP3) expressed in E. coli, purified and formulated with CFA/IFA, only VP1 elicited mouse antibody responses with measurable EV71-specific virus neutralization titers. Immunization of mice with either a DNA plasmid containing VP1 gene or VP1 expressed in Salmonella typhimurium also generated neutralizing antibody responses and protected animals against a live EV71 challenge. Recombinant EV71 virus-like particles (rVLP) produced from baculovirus formulated either with CFA/IFA or alum elicited good virus neutralization titers in both mice and non-human primates, and were found to be protective in the suckling mouse EV71 challenge model. Synthetic peptides or recombinant EV71 subunit vaccines (rVP1 and rVLP) formulated in alum were found to be poorly immunogenic in rabbits. Only formalin-inactivated (FI) EV71 virions formulated in alum elicited cross-neutralizing antibodies against different EV71 genotypes in mice, rabbits and non-human primates but induced weak neutralizing responses against CAV16. From a regulatory, economic and market acceptability standpoint, FI-EV71 virion vaccines are the most promising candidates and are currently being evaluated in human clinical trials. We further describe and analyze some new bioprocesses technologies that have great potential applications in EV71 vaccine development. This review also demonstrates the opportunities and challenges that the Asian vaccine industry faces today. PMID:22992566

  19. Production of EV71 vaccine candidates

    PubMed Central

    Chong, Pele; Hsieh, Shih-Yang; Liu, Chia-Chyi; Chou, Ai-Hsiang; Chang, Jui-Yuan; Wu, Suh-Chin; Liu, Shih-Jen; Chow, Yen-Hung; Su, Ih-Jen; Klein, Michel

    2012-01-01

    Enterovirus 71 (EV71) is now recognized as an emerging neurotropic virus in Asia and with Coxsackie virus (CV) it is the other major causative agent of hand-foot-mouth diseases (HFMD). Effective medications and/or prophylactic vaccines against HFMD are urgently needed. From a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of different EV71 vaccine candidates that have been produced and evaluated in animal models. Epitope-based synthetic peptide vaccine candidates containing residues 211–225 of VP1 formulated with Freund’s adjuvant (CFA/IFA) elicited low EV71 virus neutralizing antibody responses, but were protective in the suckling mouse challenge model. Among recombinant EV71 subunits (rVP1, rVP2 and rVP3) expressed in E. coli, purified and formulated with CFA/IFA, only VP1 elicited mouse antibody responses with measurable EV71-specific virus neutralization titers. Immunization of mice with either a DNA plasmid containing VP1 gene or VP1 expressed in Salmonella typhimurium also generated neutralizing antibody responses and protected animals against a live EV71 challenge. Recombinant EV71 virus-like particles (rVLP) produced from baculovirus formulated either with CFA/IFA or alum elicited good virus neutralization titers in both mice and non-human primates, and were found to be protective in the suckling mouse EV71 challenge model. Synthetic peptides or recombinant EV71 subunit vaccines (rVP1 and rVLP) formulated in alum were found to be poorly immunogenic in rabbits. Only formalin-inactivated (FI) EV71 virions formulated in alum elicited cross-neutralizing antibodies against different EV71 genotypes in mice, rabbits and non-human primates but induced weak neutralizing responses against CAV16. From a regulatory, economic and market acceptability standpoint, FI-EV71 virion vaccines are the most promising candidates and are currently being evaluated in human clinical trials. We further describe and analyze some new bioprocesses technologies that have great potential applications in EV71 vaccine development. This review also demonstrates the opportunities and challenges that the Asian vaccine industry faces today. PMID:22992566

  20. Biological and phylogenetic characterization of a genotype VII Newcastle disease virus from Venezuela: Efficacy of vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we describe the characterization a virulent genotype VII Newcastle disease virus (NDV) from Venezuela and evaluate the efficacy of heterologous genotype commercial vaccination under field and controlled rearing conditions. Biological pathotyping and molecular analysis were applied. Results sh...

  1. 63 FR 25869 - In the Matter of Certain Recombinantly Produced Hepatitis B Vaccines and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    1998-05-11

    ...Matter of Certain Recombinantly Produced Hepatitis B Vaccines and Products Containing Same...importation of certain recombinantly produced Hepatitis B vaccines, and products containing...importation of certain recombinantly produced Hepatitis B vaccines, or products containing...

  2. Hybrid viral vectors for vaccine and antibody production in plants.

    PubMed

    Yusibov, Vidadi; Streatfield, Stephen J; Kushnir, Natasha; Roy, Gourgopal; Padmanaban, Annamalai

    2013-01-01

    Plants have a demonstrated potential for large-scale, rapid production of recombinant proteins for diverse product applications, including subunit vaccines and monoclonal antibodies. In this field, the accent has recently shifted from the engineering of "edible" vaccines based on stable expression of target protein in transgenic or transplastomic plants to the development of purified formulated vaccines that are delivered via injection. The injectable vaccines are commonly produced using transient expression of target gene delivered into genetically unmodified plant host via viral or bacterial vectors. Most viral vectors are based on plant RNA viruses, where nonessential sequences are replaced with the gene of interest. Utilization of viral hybrids that consist of genes and regulatory elements of different virus species, or transcomplementation systems (vector/transgene) had a substantial impact on the level of target protein expression. Development and introduction of agroviral hybrid vectors that combine genetic elements of bacterial binary plasmids and plant viral vectors, and agroinfiltration as a tool of the vector delivery have resulted in significant progress in large-scale production of recombinant vaccines and monoclonal antibodies in plants. This article presents an overview of plant hybrid viral vector expression systems developed so far. PMID:23394571

  3. Ontology-supported research on vaccine efficacy, safety and integrative biological networks.

    PubMed

    He, Yongqun

    2014-07-01

    While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Several community-based ontologies (including Vaccine Ontology, Ontology of Adverse Events and Ontology of Vaccine Adverse Events) have been developed to support vaccine and adverse event representation, classification, data integration, literature mining of host-vaccine interaction networks, and analysis of vaccine adverse events. The author further proposes minimal vaccine information standards and their ontology representations, ontology-based linked open vaccine data and meta-analysis, an integrative One Network ('OneNet') Theory of Life, and ontology-based approaches to study and apply the OneNet theory. In the Big Data era, these proposed strategies provide a novel framework for advanced data integration and analysis of fundamental biological networks including vaccine immune mechanisms. PMID:24909153

  4. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

    SciTech Connect

    Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

    2011-09-22

    The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines.

  5. Insect larvae biofactories as a platform for influenza vaccine production

    Microsoft Academic Search

    E. Gomez-Casado; S. Gomez-Sebastian; M. C. Núñez; R. Lasa-Covarrubias; S. Martínez-Pulgarín; J. M. Escribano

    2011-01-01

    Increased production capacity is one of the most important priorities for seasonal and pandemic influenza vaccines. In the present study, we used a baculovirus-insect larvae system (considered small, living biofactories) to improve the production of recombinant influenza virus H1N1 hemagglutinin (HA). Insect larvae produced four-fold more HA protein than insect cells per biomass unit (1g of fresh larvae weight). A

  6. Production of Hydrogen via Biological Processes

    Microsoft Academic Search

    M. Balat

    2009-01-01

    This article reviews biological production processes of hydrogen as a renewable and alternative energy source. Biological hydrogen produced from renewable sources (biomass, water, and organic wastes) either biologically or photo-biologically is called “biohydrogen.” The phenomenon of biological hydrogen production was observed one century ago. When the oil crisis broke out in 1970s, the technology started receiving attention, especially in hydrogen

  7. Challenges in manufacturing adenoviral vectors for global vaccine product deployment.

    PubMed

    Vellinga, Jort; Smith, J Patrick; Lipiec, Agnieszka; Majhen, Dragomira; Lemckert, Angelique; van Ooij, Mark; Ives, Paul; Yallop, Christopher; Custers, Jerome; Havenga, Menzo

    2014-04-01

    Abstract Once adenovirus vector-based vaccines are licensed for the prevention of important infectious diseases, manufacturing processes capable of reliably delivering large numbers of vaccine doses will be required. The highest burden of disease for many infectious pathogens under investigation occurs in resource-poor settings. Therefore, the price per dose will be an important determinant of success. This review describes common practices for manufacturing replication-incompetent adenovirus vectors at clinical scale. Recent innovations and strategies aimed at improving the cost-effectiveness of manufacturing and ensuring high-volume vaccine production and purification are described. Hereto, technologies to increase bioreactor yields are reviewed. In addition, the use of single-use perfusion bioreactors, modification of some purification steps to avoid the use of expensive endonucleases, and use of charged filters during anion exchange all have the potential to bring down the cost of goods and are thus described. Finally, processes for ensuring quality throughout the manufacturing process, methods for testing viral identity, and safety of master seeds through to the end vaccine product are described. PMID:24593243

  8. Insect larvae biofactories as a platform for influenza vaccine production.

    PubMed

    Gomez-Casado, E; Gomez-Sebastian, S; Núñez, M C; Lasa-Covarrubias, R; Martínez-Pulgarín, S; Escribano, J M

    2011-09-01

    Increased production capacity is one of the most important priorities for seasonal and pandemic influenza vaccines. In the present study, we used a baculovirus-insect larvae system (considered small, living biofactories) to improve the production of recombinant influenza virus H1N1 hemagglutinin (HA). Insect larvae produced four-fold more HA protein than insect cells per biomass unit (1 g of fresh larvae weight). A single infected Trichoplusia ni larva produced up to 113 ?g of soluble and easily purified recombinant HA, an amount similar to that produced by 1.2×10(8) Sf21 insect cells infected by the same baculovirus. The use of the KDEL endoplasmic reticulum retention signal fused to the HA protein further increased recombinant protein production. Larvae-derived HA was immunogenically functional in vaccinated mice, inducing the generation of hemagglutination inhibition antibodies and a protective immune response against a lethal challenge with a highly virulent virus. The productivity, scalability and cost efficiency of small, living biofactories based on insect larvae suggest a broad-based strategy for the production of recombinant subunit vaccines against seasonal or pandemic influenza as an alternative to fermentation technologies. PMID:21421054

  9. Translational research on vaccines: influenza as an example.

    PubMed

    Belshe, R B

    2007-12-01

    Influenza vaccine development is reviewed as an example of ongoing translational research, which is moving fundamental advances in biology into useful products. The types of new influenza vaccines span the gamut of modern biology research and include new methods of vaccine production (tissue culture compared with egg-produced vaccine). New vaccines being studied include recombinant proteins, polynucleotide vaccines, conjugate vaccines, peptides, expression vectors, and live attenuated vaccines; new adjuvants are being explored to reduce the quantity of antigen needed. The benefits of using reverse genetics are explored. The limits of translational research for predicting clinical results after wide use of vaccines are discussed, including one example of "overinterpretation" of data; some questions should be left to phase IV experience to answer. The pipeline for new influenza vaccines is robust, and recent investment by government and industry in newer vaccines will bring several new products to clinical use. PMID:17971813

  10. Development, Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

    PubMed Central

    Cui, Fuqiang; Liang, Xiaofeng; Wang, Fuzhen; Zheng, Hui; Hutin, Yvan J; Yang, Weizhong

    2014-01-01

    China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted. PMID:24681843

  11. Modeling Shrimp Biomass and Viral Infection for Production of Biological Countermeasures

    E-print Network

    Modeling Shrimp Biomass and Viral Infection for Production of Biological Countermeasures H. T of large quantities of therapeutic and/or preventative countermeasures. We couple equations for biomass machinery in an existing biomass for the production of a vaccine or antibody by infection using a virus

  12. Synthetic Biology Guides Biofuel Production

    PubMed Central

    Connor, Michael R.; Atsumi, Shota

    2010-01-01

    The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges. PMID:20827393

  13. A probabilistic model for risk assessment of residual host cell DNA in biological products.

    PubMed

    Yang, Harry; Zhang, Lanju; Galinski, Mark

    2010-04-26

    Biological products such as viral vaccines manufactured in cells contain residual DNA derived from host cell substrates used in production. It is theoretically possible that the residual DNA could transmit activated oncogenes and/or latent infectious viral genomes to subjects receiving the product, and induce oncogenic or infective events. A probabilistic model to estimate the risks due to residual DNA is proposed. The model takes account of enzyme inactivation process. It allows for more accurate risk assessment when compared to methods currently in use. An application of the method to determine safety factor of a vaccine product is provided. PMID:20226252

  14. Hepatitis B Vaccine

    MedlinePLUS

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Hepatitis B vaccine: Why get vaccinated?Hepatitis B vaccine can prevent hepatitis B, and the serious consequences of hepatitis ...

  15. Development of a Salmonella cross-protective vaccine for food animal production systems.

    PubMed

    Heithoff, Douglas M; House, John K; Thomson, Peter C; Mahan, Michael J

    2015-01-01

    Intensive livestock production is associated with increased Salmonella exposure, transmission, animal disease, and contamination of food and water supplies. Modified live Salmonella enterica vaccines that lack a functional DNA adenine methylase (Dam) confer cross-protection to a diversity of salmonellae in experimental models of murine, avian, ovine, and bovine models of salmonellosis. However, the commercial success of any vaccine is dependent upon the therapeutic index, the ratio of safety/efficacy. Herein, secondary virulence-attenuating mutations targeted to genes involved in intracellular and/or systemic survival were introduced into Salmonella dam vaccines to screen for vaccine candidates that were safe in the animal and the environment, while maintaining the capacity to confer cross-protective immunity to pathogenic salmonellae serotypes. Salmonella dam mgtC, dam sifA, and dam spvB vaccine strains exhibited significantly improved vaccine safety as evidenced by the failure to give rise to virulent revertants during the infective process, contrary to the parental Salmonella dam vaccine. Further, these vaccines exhibited a low grade persistence in host tissues that was associated with reduced vaccine shedding, reduced environmental persistence, and induction of cross-protective immunity to pathogenic serotypes derived from infected livestock. These data indicate that Salmonella dam double mutant vaccines are suitable for commercial applications against salmonellosis in livestock production systems. Reducing pre-harvest salmonellae load through vaccination will promote the health and productivity of livestock and reduce contamination of livestock-derived food products, while enhancing overall food safety. PMID:25448106

  16. Can increasing adult vaccination rates reduce lost time and increase productivity?

    PubMed

    Rittle, Chad

    2014-12-01

    This article addresses limited vaccination coverage by providing an overview of the epidemiology of influenza, pertussis, and pneumonia, and the impact these diseases have on work attendance for the worker, the worker's family, and employer profit. Studies focused on the cost of vaccination programs, lost work time, lost employee productivity and acute disease treatment are discussed, as well as strategies for increasing vaccination coverage to reduce overall health care costs for employers. Communicating the benefits of universal vaccination for employees and their families and combating vaccine misinformation among employees are outlined. [Workplace Health Saf 2014;62(12):508-515.]. PMID:25216055

  17. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

    PubMed

    Haese, Nicole; Brocato, Rebecca L; Henderson, Thomas; Nilles, Matthew L; Kwilas, Steve A; Josleyn, Matthew D; Hammerbeck, Christopher D; Schiltz, James; Royals, Michael; Ballantyne, John; Hooper, Jay W; Bradley, David S

    2015-06-01

    Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgY?Fc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of IgY and IgY?Fc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. ?-ANDV immune sera, or IgY/IgY?Fc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both immune sera, and egg-derived purified IgY/IgY?Fc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgY?Fc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product capable of preventing a lethal disease when administered post-exposure. PMID:26046641

  18. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure

    PubMed Central

    Henderson, Thomas; Nilles, Matthew L.; Kwilas, Steve A.; Josleyn, Matthew D.; Hammerbeck, Christopher D.; Schiltz, James; Royals, Michael; Ballantyne, John; Hooper, Jay W.; Bradley, David S.

    2015-01-01

    Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgY?Fc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of IgY and IgY?Fc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. ?-ANDV immune sera, or IgY/IgY?Fc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both immune sera, and egg-derived purified IgY/IgY?Fc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgY?Fc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product capable of preventing a lethal disease when administered post-exposure. PMID:26046641

  19. A controllable bacterial lysis system to enhance biological safety of live attenuated Vibrio anguillarum vaccine.

    PubMed

    Chu, Teng; Guan, Lingyu; Shang, Pengfei; Wang, Qiyao; Xiao, Jingfan; Liu, Qin; Zhang, Yuanxing

    2015-08-01

    Bacterial strains used as backbone for the generation of vaccine prototypes should exhibit an adequate and stable safety profile. Given the fact that live attenuated vaccines often contain some potential risks in virulence recovery and spread infections, new approaches are greatly needed to improve their biological safety. Here, a critically iron-regulated promoter PviuA was screened from Vibrio anguillarum, which was demonstrated to respond to iron-limitation signal both in vitro and in vivo. By using PviuA as a regulatory switch to control the expression of phage P22 lysis cassette 13-19-15, a novel in vivo inducible bacterial lysis system was established in V. anguillarum. This system was proved to be activated by iron-limitation signals and then effectively lyse V. anguillarum both in vitro and in vivo. Further, this controllable bacterial lysis system, after being transformed into a live attenuated V. anguillarum vaccine strain MVAV6203, was confirmed to significantly improve biological safety of the live attenuated vaccine without impairing its immune protection efficacy. PMID:26052008

  20. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product,...

  1. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product,...

  2. [Book review] Developments in biological standardization (Vol. 49): Fish Biologics: Seriodiagnostics and Vaccines, edited by W. Hennessen and D. P. Andersen

    USGS Publications Warehouse

    Anderson, D.P.

    1981-01-01

    Review of: Developments in Biologicals, Vol. 49. Fish Biologics: Serodiagnostics and Vaccines. International Symposium, Leetown, W.Va., April 1981. Editor(s): Hennessen, W. (Bern); Andersen, D.P. (Leetown, W.Va.); Society/Societies: International Association of Biological Standardization, XII + 496 p., 90 fig., 110 tab., soft cover, 1981. ISBN: 978-3-8055-3471-0.

  3. [Viral safety of biological medicinal products].

    PubMed

    Stühler, A; Blümel, J

    2014-10-01

    Viral safety of blood donations, plasma products, viral vaccines and gene therapy medicinal products, biotechnical-derived products and tissue and cell therapy products is a particular challenge. These products are manufactured using a variety of human or animal-derived starting materials and reagents; therefore, extensive testing of donors and of cell banks established for production is required. Furthermore, the viral safety of reagents, such as bovine sera, porcine trypsin and human transferrin or albumin needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced; however, sometimes it is not possible to introduce such steps for tissues or cell-based medicinal products as the activity and viability of cells will be compromised. It might be possible to implement steps for inactivation or removal of potential contaminating enveloped viruses only for production of small and stable non-enveloped viral gene vectors. PMID:25123140

  4. Biological Safety Cabinets n Product protection

    E-print Network

    Collins, Gary S.

    2.7 #12;Biological Safety Cabinets Purpose n Product protection n Personal protection n Environmental protection 2.7 #12;Biological Safety Cabinets Types A. Class I n inward airflow protects worker n exhaust to outside (w/wo HEPA filter) B. Class II n worker, product, environmental protection n "sterile

  5. Vaccine process technology.

    PubMed

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory perspective, Quality by Design (QbD) and Process Analytical Technology (PAT) are important initiatives that can be applied effectively to many types of vaccine processes. Universal demand for vaccines requires that a manufacturer plan to supply tens and sometimes hundreds of millions of doses per year at low cost. To enable broader use, there is intense interest in improving temperature stability to allow for excursions from a rigid cold chain supply, especially at the point of vaccination. Finally, there is progress in novel routes of delivery to move away from the traditional intramuscular injection by syringe approach. PMID:22407777

  6. Toxicology/Cell Biology Ruminant Production

    E-print Network

    Langerhans, Brian

    Ken Adler Toxicology/Cell Biology MBS Mark Alley Ruminant Production PHP Glen Almond Swine Health & Production PHP Kevin Anderson Ruminant Production PHP Nigel Campbell Anesthesiology MBS Wolfgang Baeumer Fogle Immunology PHP Michael Dykstra Electron Microscopy PHP Derek Foster Ruminant Medicine PHP Kelli

  7. Biological production of products from waste gases

    DOEpatents

    Gaddy, James L. (Fayetteville, AR)

    2002-01-22

    A method and apparatus are designed for converting waste gases from industrial processes such as oil refining, and carbon black, coke, ammonia, and methanol production, into useful products. The method includes introducing the waste gases into a bioreactor where they are fermented to various products, such as organic acids, alcohols, hydrogen, single cell protein, and salts of organic acids by anaerobic bacteria within the bioreactor. These valuable end products are then recovered, separated and purified.

  8. Three Rs Approaches in the Production and Quality Control of Fish Vaccines.

    PubMed

    Midtlyng, Paul J; Hendriksen, Coenraad; Balks, Elisabeth; Bruckner, Lukas; Elsken, Lawrence; Evensen, Oystein; Fyrand, Kjetil; Guy, Allison; Halder, Marlies; Hawkins, Penny; Kisen, Gunn; Romstad, Anne Berit; Salonius, Kira; Smith, Patrick; Sneddon, Lynne U

    2011-03-01

    The workshop on Three Rs Approaches in the Production and Quality Control of Fish Vaccines aimed a) to identify animal tests currently stipulated for the production and quality control of fish vaccines and to highlight animal welfare concerns associated with these tests; b) to identify viable options to replace, reduce, and refine animal use for fish vaccine testing; and c) to discuss the way forward and set out how the Three Rs may be implemented without jeopardizing the quality of the vaccines. The workshop participants - experts from academia, regulatory authorities, a scientific animal welfare organization, and the fish vaccine industry - agreed that efforts should be undertaken to replace the vaccination-challenge batch potency testing with tests based on antigen quantification or antibody response tests. Regulatory requirements of questionable scientific value and relevance for the quality of fish vaccines, such as the re-testing of batches produced outside Europe, or the double-dose batch safety test, should be re-considered. As an immediate measure the design of the current animal tests should be evaluated and modified in the light of refinement and reduction, for example, the number of unprotected control fish in vaccination-challenge tests should be reduced to the minimum. PMID:21371907

  9. Establishment of pandemic influenza vaccine production capacity at Bio Farma, Indonesia.

    PubMed

    Suhardono, Mahendra; Ugiyadi, Dori; Nurnaeni, Ida; Emelia, Imelda

    2011-07-01

    In Indonesia, avian influenza A(H5N1) virus started to spread in humans in June 2005, with an alarming case-fatality rate of more than 80%. Considering that global influenza vaccine production capacity would barely have covered 10% of the world's pandemic vaccine needs, and that countries with no production facilities or prearranged contracts would be without access to a vaccine, the Government of Indonesia embarked on a programme to increase its readiness for a future influenza pandemic. This included the domestic production of influenza vaccine, which was entrusted to Bio Farma. This health security strategy consists of developing trivalent influenza vaccine production capacity in order to be able to convert immediately to monovalent production of up to 20 million pandemic doses for the Indonesian market upon receipt of the seed strain from the World Health Organization (WHO). For this purpose, a dedicated production facility is being constructed within the Bio Farma premises in Bandung. As an initial stage of influenza vaccine development, imported seasonal influenza bulk has been formulated and filled in the Bio Farma facility. Following three consecutive batches and successful clinical trials, the product was licensed by the Indonesian National Regulatory Authority and distributed commercially for the Hajj programme in 2009. With continued support from its technology transfer partners, Bio Farma is now advancing with the development of upstream processes to produce its own bulk for seasonal and pandemic use. PMID:21684423

  10. Assessment of packed bed bioreactor systems in the production of viral vaccines.

    PubMed

    Rajendran, Ramya; Lingala, Rajendra; Vuppu, Siva Kumar; Bandi, Bala Obulapathi; Manickam, Elaiyaraja; Macherla, Sankar Rao; Dubois, Stéphanie; Havelange, Nicolas; Maithal, Kapil

    2014-01-01

    Vaccination is believed to be the most effective method for the prevention of infectious diseases. Thus it is imperative to develop cost effective and scalable process for the production of vaccines so as to make them affordable for mass use. In this study, performance of a novel disposable iCELLis fixed bed bioreactor system was investigated for the production of some viral vaccines like Rabies, Hepatitis-A and Chikungunya vaccines in comparison to conventional systems like the commercially available packed bed system and roller bottle system. Vero and MRC-5 cell substrates were evaluated for growth parameters in all the three systems maintaining similar seeding density, multiplicity of infection (MOI) and media components. It was observed that Vero cells showed similar growth in all the three bioreactors whereas MRC-5 cells showed better growth in iCELLis Nano system and roller bottle system. Subsequently, the virus infection and antigen production studies also revealed that for Hepatitis-A and Chikungunya iCELLis Nano bioreactor system was better to the commercial packed bed bioreactor and roller bottle systems. Although for rabies antigen production commercially available packed bed bioreactor system was found to be better. This study shows that different bioreactor platforms may be employed for viral vaccine production and iCELLis Nano is one of such new convenient and a stable platform for production of human viral vaccines. PMID:24949260

  11. Use of Staby(®) technology for development and production of DNA vaccines free of antibiotic resistance gene.

    PubMed

    Reschner, Anca; Scohy, Sophie; Vandermeulen, Gaëlle; Daukandt, Marc; Jacques, Céline; Michel, Benjamin; Nauwynck, Hans; Xhonneux, Florence; Préat, Véronique; Vanderplasschen, Alain; Szpirer, Cédric

    2013-10-01

    The appearance of new viruses and the cost of developing certain vaccines require that new vaccination strategies now have to be developed. DNA vaccination seems to be a particularly promising method. For this application, plasmid DNA is injected into the subject (man or animal). This plasmid DNA encodes an antigen that will be expressed by the cells of the subject. In addition to the antigen, the plasmid also encodes a resistance to an antibiotic, which is used during the construction and production steps of the plasmid. However, regulatory agencies (FDA, USDA and EMA) recommend to avoid the use of antibiotics resistance genes. Delphi Genetics developed the Staby(®) technology to replace the antibiotic-resistance gene by a selection system that relies on two bacterial genes. These genes are small in size (approximately 200 to 300 bases each) and consequently encode two small proteins. They are naturally present in the genomes of bacteria and on plasmids. The technology is already used successfully for production of recombinant proteins to achieve higher yields and without the need of antibiotics. In the field of DNA vaccines, we have now the first data validating the innocuousness of this Staby(®) technology for eukaryotic cells and the feasibility of an industrial production of an antibiotic-free DNA vaccine. Moreover, as a proof of concept, mice have been successfully vaccinated with our antibiotic-free DNA vaccine against a deadly disease, pseudorabies (induced by Suid herpesvirus-1). PMID:24051431

  12. Developing whole mycobacteria cell vaccines for tuberculosis: Workshop proceedings, Max Planck Institute for Infection Biology, Berlin, Germany, July 9, 2014.

    PubMed

    2015-06-12

    On July 9, 2014, Aeras and the Max Planck Institute for Infection Biology convened a workshop entitled "Whole Mycobacteria Cell Vaccines for Tuberculosis" at the Max Planck Institute for Infection Biology on the grounds of the Charité Hospital in Berlin, Germany, close to the laboratory where, in 1882, Robert Koch first identified Mycobacterium tuberculosis (Mtb) as the pathogen responsible for tuberculosis (TB). The purpose of the meeting was to discuss progress in the development of TB vaccines based on whole mycobacteria cells. Live whole cell TB vaccines discussed at this meeting were derived from Mtb itself, from Bacille Calmette-Guérin (BCG), the only licensed vaccine against TB, which was genetically modified to reduce pathogenicity and increase immunogenicity, or from commensal non-tuberculous mycobacteria. Inactivated whole cell TB and non-tuberculous mycobacterial vaccines, intended as immunotherapy or as safer immunization alternatives for HIV+ individuals, also were discussed. Workshop participants agreed that TB vaccine development is significantly hampered by imperfect animal models, unknown immune correlates of protection and the absence of a human challenge model. Although a more effective TB vaccine is needed to replace or enhance the limited effectiveness of BCG in all age groups, members of the workshop concurred that an effective vaccine would have the greatest impact on TB control when administered to adolescents and adults, and that use of whole mycobacteria cells as TB vaccine candidates merits greater support, particularly given the limited understanding of the specific Mtb antigens necessary to generate an immune response capable of preventing Mtb infection and/or disease. PMID:25882170

  13. Natural production of biological optical systems

    NASA Astrophysics Data System (ADS)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

    Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

  14. IRRIGATION TO MAXIMIZE VACCINE ANTIGEN PRODUCTION IN PHARMACEUTICAL TOBACCO

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biotechnology companies have engineered plants to produce recombinant proteins for therapeutic drugs and vaccines. Chlorogen, Inc. located in St. Louis, Missouri, inserted the protective antigen (PA) gene from Bacillus anthracis into tobacco (Nicotiana tabacum) chloroplasts to produce an anthrax va...

  15. 9 CFR 114.17 - Rebottling of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The...

  16. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.4 Identification of biological products. Suitable...

  17. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.4 Identification of biological products. Suitable...

  18. 9 CFR 114.17 - Rebottling of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The...

  19. 9 CFR 114.18 - Reprocessing of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The...

  20. Casting off vaccine supply charity -- the pace quickens. CVI goal: quality vaccines for all children.

    PubMed

    1995-10-01

    Several proposals are offered for production of high-quality vaccines within developing countries. The World Health Organization's Vaccine Supply and Quality (VSQ) team from the Global Program for Vaccines and Immunization (GPV) visited 10 countries (Bangladesh, Brazil, Egypt, India, Indonesia, Iran, Mexico, Pakistan, Philippines, and South Africa) out of 14 priority countries (China, Russia, Thailand, and Vietnam were not visited) producing vaccines and found only two with a quality control system that was acceptable. Vaccine-producing countries are urged to consider the full costs of production that include necessary infrastructure, an independent national control authority and laboratory, manufacturers with managerial autonomy, and manufacturers with good management, a qualified staff, and adequate technology. UNICEF has urged both private and public sectors to combine forces in bringing down the price of new vaccines for distribution to a very large market. Some imaginative proposals were made by some manufacturers for vaccine production and supply for a range of less traditional vaccines. The Director of the Massachusetts Public Health Biologic Laboratories proposed the formation of a consortium of vaccine manufacturers who would support public health priorities for market-affordable, simple vaccines against the major childhood diseases. The aim would be international validation of high-quality local vaccine production in developing countries, ease of research collaboration, improvement in information exchange between countries, and structured assistance. Lack of political commitment has been blamed for poor quality local production. A small cooperative effort among some Latin American countries, the Pan American Association's Regional Vaccine System for Latin America (SIREVA), is backed by the Children's Vaccine Initiative. SIREVA is a consortium of manufacturers in Brazil, Chile, and Mexico that plans joint development of some vaccines. Donor assistance is suggested for UNICEF's new targeting strategy and global vaccine fund for well-defined and specific needs. UNICEF is the main distributor of vaccines to developing countries and aims for program sustainability and distribution of the new vaccines. PMID:12290725

  1. Influenza vaccine production for Brazil: a classic example of successful North-South bilateral technology transfer.

    PubMed

    Miyaki, Cosue; Meros, Mauricio; Precioso, Alexander R; Raw, Isaias

    2011-07-01

    Technology transfer is a promising approach to increase vaccine production at an affordable price in developing countries. In the case of influenza, it is imperative that developing countries acquire the technology to produce pandemic vaccines through the transfer of know-how, as this will be the only way for the majority of these countries to face the huge demand for vaccine created by influenza pandemics. Access to domestically produced influenza vaccine in such health crises is thus an important national defence strategy. However, technology transfer is not a simple undertaking. It requires a committed provider who is willing to transfer a complete production process, and not just the formulation and fill-finish parts of the process. It requires a recipient with established experience in vaccine production for human use and the ability to conduct research into new developments. In addition, the country of the recipient should preferably have sufficient financial resources to support the undertaking, and an internal market for the new vaccine. Technology transfer should create a solid partnership that results in the joint development of new competency, improvements to the product, and to further innovation. The Instituto Butantan-sanofi pasteur partnership can be seen as a model for successful technology transfer and has led to the technological independence of the Instituto Butantan in the use a strategic public health tool. PMID:21684420

  2. [An update on vaccines. Theory, realities and myths (I)].

    PubMed

    Martínez-Mateo, P; Bustos-Fonseca, M J; Gil-Díaz, M J

    2012-04-01

    Vaccines are biological products used to achieve active artificial immunization. Nowadays, vaccines are increasingly powerful, effective and safe. The list of vaccine-preventable diseases is expanding, which together with the increasing population likely to be vaccinated, it is expected that vaccine products will increase this century. This article is a brief but practical overview of the concept and types of vaccines, advances that have taken place recent decades on the fundamentals of the immune response and vaccine components (including the role of adjuvants). These concepts give rise to the criteria for when and how to vaccinate, to whom and why not to do it. With the hope that this text is useful, it ends with a brief overview as to why there are people who refuse vaccinations. PMID:24895720

  3. Large-scale production in Pichia pastoris of the recombinant vaccine Gavac against cattle tick.

    PubMed

    Canales, M; Enríquez, A; Ramos, E; Cabrera, D; Dandie, H; Soto, A; Falcón, V; Rodríguez, M; de la Fuente, J

    1997-03-01

    A gene coding for the Bm86 tick protein was recently cloned, expressed in Pichia pastoris and shown to induce an inmunological response in cattle against ticks. Moreover, the Gavac vaccine (Heber Biotec S.A., Havana, Cuba), which contains this recombinant protein, has proved to control the Boophilus microplus populations under field conditions. This paper reviews the development and large-scale production of this vaccine, the efficacy of the resulting product and the strategy followed in designing its production plant. The production plant fulfills biosafety requirements and GMP. PMID:9141213

  4. A Cell-Based Systems Biology Assessment of Human Blood to Monitor Immune Responses after Influenza Vaccination

    PubMed Central

    Hoek, Kristen L.; Samir, Parimal; Howard, Leigh M.; Niu, Xinnan; Prasad, Nripesh; Galassie, Allison; Liu, Qi; Allos, Tara M.; Floyd, Kyle A.; Guo, Yan; Shyr, Yu; Levy, Shawn E.; Joyce, Sebastian; Edwards, Kathryn M.; Link, Andrew J.

    2015-01-01

    Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses. PMID:25706537

  5. A cell-based systems biology assessment of human blood to monitor immune responses after influenza vaccination.

    PubMed

    Hoek, Kristen L; Samir, Parimal; Howard, Leigh M; Niu, Xinnan; Prasad, Nripesh; Galassie, Allison; Liu, Qi; Allos, Tara M; Floyd, Kyle A; Guo, Yan; Shyr, Yu; Levy, Shawn E; Joyce, Sebastian; Edwards, Kathryn M; Link, Andrew J

    2015-01-01

    Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses. PMID:25706537

  6. Design of clinical trials for therapeutic cancer vaccines development

    Microsoft Academic Search

    Jacek Mackiewicz; Andrzej Mackiewicz

    2009-01-01

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and\\/or gene therapy products category.

  7. Good Manufacturing Practices production and analysis of a DNA vaccine against dental caries

    Microsoft Academic Search

    Ya-ping Yang; Yu-hong Li; Ai-hua Zhang; Lan Bi; Ming-wen Fan

    2009-01-01

    Aim:To prepare a clinical-grade anti-caries DNA vaccine pGJA-P\\/VAX and explore its immune effect and protective efficacy against a cariogenic bacterial challenge.Methods:A large-scale industrial production process was developed under Good Manufacturing Practices (GMP) by combining and optimizing common unit operations such as alkaline lysis, precipitation, endotoxin removal and column chromatography. Quality controls of the purified bulk and final lyophilized vaccine were

  8. Mass production and standardization of Clostridium oedematiens vaccine against black disease (infectious necrotic hepatitis) of sheep.

    PubMed

    Ardehali, M; Darakhshan, H; Moosawi, M

    1986-01-01

    The object of this study was to prepare a potent vaccine against black disease of sheep. Attempts were made to prepare and formulate the ingredients in order to obtain high yield of toxin. A 600 litre batch of mass production of Clostridium oedematiens (Cl. novyi) vaccine was prepared with ingredients consisting of 4% peptone, 0.25% NaCl, 0.5% liver extract, 0.1% L-cysteine, 1% maltose, 0.02% sodium dithionite and 0.25% ferrous sulphate solution. The prepared vaccine was diluted to concentrations of 20, 40, 60 and 80 per cent of antigens. Potassium alum was added as an adjuvant. The potency test of the prepared vaccine was determined in a group of forty rabbits according to the British Pharmacopoeia (Veterinary). Maximum titre was obtained at 80 per cent with the level of 33 units per ml of alpha antitoxin in rabbits pooled serum. 20, 16 and 8 units per ml of alpha antitoxin were obtained respectively for 60, 40 and 20 per cent of diluted antigen in rabbits pooled serum. Sheep have been vaccinated in black disease areas with this vaccine. Reports obtained from the field indicate that black disease in sheep could be effectively controlled by this vaccine in Iran. PMID:3792643

  9. The three Rs of Russell & Burch and the testing of biological products.

    PubMed

    Balls, M; Straughan, D W

    1996-01-01

    The principles of humane animal experimentation proposed by Russell & Burch (1959), namely, replacement, reduction, and refinement, are now commonly known as the Three Rs. These principles are clearly embodied in Article 7 of Directive 86/609/EEC. It is instructive, therefore, to consider the priority currently attached to compliance with these principles and to the Directive in the development and control of biological products. Specific comments are made on the need for the application of the Three Rs in relation to the testing of human diphtheria and tetanus vaccines, human pertussis vaccine, inactivated veterinary Gumboro vaccine, veterinary Newcastle disease vaccine, veterinary clostridial vaccines and botulinum toxin. We pose three questions: a. Are the minimum numbers of animals already being used in this area? b. Is any unnecessary pain, suffering, distress or lasting harm being inflicted on the animals used? and c. What could and should be done about any shortcomings in current practice? Finally, the role of ECVAM in the promotion of the Three Rs within the European Union will be reviewed. PMID:8785939

  10. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...provided in this section, experimental biological products...authorize the preparation of experimental products on the premises...permission to prepare an experimental biological product on...submitted to the Administrator. Research facilities that are...

  11. Advances and challenges in the development and production of effective plant-based influenza vaccines.

    PubMed

    Yusibov, Vidadi; Kushnir, Natasha; Streatfield, Stephen J

    2015-04-01

    Influenza infections continue to present a major threat to public health. Traditional modes of influenza vaccine manufacturing are failing to satisfy the global demand because of limited scalability and long production timelines. In contrast, subunit vaccines (SUVs) can be produced in heterologous expression systems in shorter times and at higher quantities. Plants are emerging as a promising platform for SUV production due to time efficiency, scalability, lack of harbored mammalian pathogens and possession of the machinery for eukaryotic post-translational protein modifications. So far, several organizations have utilized plant-based transient expression systems to produce SUVs against influenza, including vaccines based on virus-like particles. Plant-produced influenza SUV candidates have been extensively evaluated in animal models and some have shown safety and immunogenicity in clinical trials. Here, the authors review ongoing efforts and challenges to producing influenza SUV candidates in plants and discuss the likelihood of bringing these products to the market. PMID:25487788

  12. Lot-to-lot consistency of live attenuated SA 14-14-2 Japanese encephalitis vaccine manufactured in a good manufacturing practice facility and non-inferiority with respect to an earlier product.

    PubMed

    Zaman, K; Naser, Abu Mohd; Power, Maureen; Yaich, Mansour; Zhang, Lei; Ginsburg, Amy Sarah; Luby, Stephen P; Rahman, Mahmudur; Hills, Susan; Bhardwaj, Mukesh; Flores, Jorge

    2014-10-21

    We conducted a four-arm, double-blind, randomized controlled trial among 818 Bangladeshi infants between 10 and 12 months of age to establish equivalence among three lots of live attenuated SA 14-14-2 JE vaccine manufactured by the China National Biotec Group's Chengdu Institute of Biological Products (CDIBP) in a new Good Manufacturing Practice (GMP) facility and to evaluate non-inferiority of the product with a lot of the same vaccine manufactured in CDIBP's original facility. The study took place in two sites in Bangladesh, rural Matlab and Mirpur in urban Dhaka. We collected pre-vaccination (Day 0) and post-vaccination Day 28 (-4 to +14 days) blood samples to assess neutralizing anti-JE virus antibody titers in serum by plaque reduction neutralization tests (PRNT). Seroprotection following vaccination was defined as a PRNT titer ?1:10 at Day 28 in participants non-immune at baseline. Follow-up for reactogenicity and safety was conducted through home visits at Day 7 and monitoring for serious adverse events through Day 28. Seroprotection rates ranged from 80.2% to 86.3% for all four lots of vaccine. Equivalence of the seroprotection rates between pairs of vaccine lots produced in the new GMP facility was satisfied at the pre-specified 10% margin of the 95% confidence interval (CI) for two of the three pairwise comparisons, but not for the third (-4.3% observed difference with 95% CI of -11.9 to 3.3%). Nevertheless, the aggregate seroprotection rate for all three vaccine lots manufactured in the GMP facility was calculated and found to be within the non-inferiority margin (within 10%) to the vaccine lot produced in the original facility. All four lots of vaccine were safe and well tolerated. These study results should facilitate the use of SA 14-14-2 JE vaccine as a routine component of immunization programs in Asian countries. PMID:25239483

  13. H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy

    Microsoft Academic Search

    Jean-François Rahier; Pavol Papay; Julia Salleron; Shaji Sebastian; Manuela Marzo; Laurent Peyrin-Biroulet; Valle Garcia-Sanchez; Walter Fries; Dirk P van Asseldonk; Klaudia Farkas; Nanne K de Boer; Taina Sipponen; Pierre Ellul; Edouard Louis; Simon T C Peake; Uri Kopylov; Jochen Maul; Badira Makhoul; Gionata Fiorino; Yazdan Yazdanpanah; Maria Chaparro

    2011-01-01

    BackgroundSafety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and\\/or biological therapy.Aims and methodsThe authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of

  14. Production of formalinized poliomyelitis vaccine (Salk-type) on a semi-industrial scale

    PubMed Central

    Goldblum, N.; Gotlieb, Tamar; Miller, G.

    1957-01-01

    This article describes a semi-industrial method for the production of formalinized poliomyelitis vaccine developed during 1956. The general technique followed that originally devised by Salk with modifications developed locally. The vaccine was tested for safety and innocuity according to the Minimum Requirements laid down by the United States Public Health Service. Seitz filtration was found to be essential for the production of a non-infectious vaccine; filtration through glass filters proved to give inconsistent results. High initial virus titres, proper filtration methods, and the use of a sensitive tissue-culture system for safety testing were considered to be of prime importance for the production of a safe and effective vaccine. Over 60 000 infants and young children were inoculated with this vaccine in a country-wide immunization programme during the winter and spring of 1957. No untoward effects were noted; an immunological evaluation of its performance in those inoculated is in progress. ImagesFIG. 4FIG. 5 PMID:13511145

  15. Lymphocytic vasculitis associated with the anthrax vaccine: case report and review of anthrax vaccination

    Microsoft Academic Search

    Antonio E Muñiz

    2003-01-01

    Anthrax is caused by the spore-forming bacteria Bacillus anthracis. It occurs naturally, but recently has been manufactured as a biological warfare agent. This makes prophylaxis for anthrax an urgent concern and efforts are ongoing for the production of an efficient and safe vaccine. Side effects to the current anthrax vaccine are usually minor and mainly consist of local skin reactions.

  16. Levels of humoral antibodies induced by different inactivated vaccines correlate with egg production in commercial layers challenged with virulent Newcastle disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the relationship between humoral antibodies from homologous and heterologous vaccines and egg production, twenty-two week-old commercial layers previously vaccinated with four live B1 vaccines were boosted with two different inactivated Newcastle disease virus (NDV) vaccines, a virulent ...

  17. Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology

    PubMed Central

    Mahla, Ranjeet Singh; Reddy, Madhava C.; Prasad, D. Vijaya Raghava; Kumar, Himanshu

    2013-01-01

    Innate sensors play a critical role in the early innate immune responses to invading pathogens through sensing of diverse biochemical signatures also known as pathogen associated molecular patterns (PAMPs). These biochemical signatures primarily consist of a major family of biomolecules such as proteins, lipids, nitrogen bases, and sugar and its complexes, which are distinct from host molecules and exclusively expressed in pathogens and essential to their survival. The family of sensors known as pattern recognition receptors (PRRs) are germ-line encoded, evolutionarily conserved molecules, and consist of Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), C-type lectin-like receptors (CLRs), and DNA sensors. Sensing of PAMP by PRR initiates the cascade of signaling leading to the activation of transcription factors, such as NF-?B and interferon regulatory factors (IRFs), resulting in a variety of cellular responses, including the production of interferons (IFNs) and pro-inflammatory cytokines. In this review, we discuss sensing of different types of glycosylated PAMPs such as ?-glucan (a polymeric sugar) or lipopolysaccharides, nucleic acid, and so on (sugar complex PAMPs) by different families of sensors, its role in pathogenesis, and its application in development of potential vaccine and vaccine adjuvants. PMID:24032031

  18. Biological Hydrogen Production Using Synthetic Wastewater Biotin and glutamic acid are not required for biological hydrogen production.

    E-print Network

    Barthelat, Francois

    Biological Hydrogen Production Using Synthetic Wastewater Conclusion ·Biotin and glutamic acid are not required for biological hydrogen production. ·MgSO4 .7H2O is a required nutrient, but hydrogen production work should focus on minimizing the lag time in biological hydrogen production, by varying nutrient

  19. Lipid oxidation: Mechanisms, products and biological significance

    Microsoft Academic Search

    E. N. Frankel

    1984-01-01

    This paper reviews our studies of fatty acid hydroperoxides, their secondary products and mechanisms for their formation in\\u000a the context of some of their possible biological consequences. The uneven distribution of isomeric hydroperoxides in oxidized\\u000a linolenate and photosensitized oxidized linoleate is related to the formation of hydroperoxy cyclic peroxides. Interest in\\u000a the hydroperoxy mono-and bi-cycloendoperoxides from oxidized linolenate stems from

  20. Impact of Severe Weather Conditions on Biological Products

    MedlinePLUS

    ... Product Security Impact of Severe Weather Conditions on Biological Products CBER is providing interested persons with information ... storage, and should be discarded. Other Non-Blood Biologicals Requiring Refrigeration or Frozen Storage The information above ...

  1. History of vaccination

    PubMed Central

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before. PMID:25136134

  2. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.50 Ingredients of biological products. All...

  3. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.50 Ingredients of biological products. All...

  4. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients

    PubMed Central

    Hodi, F. Stephen; Mihm, Martin C.; Soiffer, Robert J.; Haluska, Frank G.; Butler, Marcus; Seiden, Michael V.; Davis, Thomas; Henry-Spires, Rochele; MacRae, Suzanne; Willman, Ann; Padera, Robert; Jaklitsch, Michael T.; Shankar, Sridhar; Chen, Teresa C.; Korman, Alan; Allison, James P.; Dranoff, Glenn

    2003-01-01

    A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity of nascent tumors contributes to this failure in host defense. Therapeutic vaccines that enhance dendritic cell presentation of cancer antigens increase specific cellular and humoral responses, thereby effectuating tumor destruction in some cases. The attenuation of T cell activation by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) further limits the potency of tumor immunity. In murine systems, the administration of antibodies that block CTLA-4 function inhibits the growth of moderately immunogenic tumors and, in combination with cancer vaccines, increases the rejection of poorly immunogenic tumors, albeit with a loss of tolerance to normal differentiation antigens. To gain a preliminary assessment of the biologic activity of antagonizing CTLA-4 function in humans, we infused a CTLA-4 blocking antibody (MDX-CTLA4) into nine previously immunized advanced cancer patients. MDX-CTLA4 stimulated extensive tumor necrosis with lymphocyte and granulocyte infiltrates in three of three metastatic melanoma patients and the reduction or stabilization of CA-125 levels in two of two metastatic ovarian carcinoma patients previously vaccinated with irradiated, autologous granulocyte–macrophage colony-stimulating factor-secreting tumor cells. MDX-CTLA4 did not elicit tumor necrosis in four of four metastatic melanoma patients previously immunized with defined melanosomal antigens. No serious toxicities directly attributable to the antibody were observed, although five of seven melanoma patients developed T cell reactivity to normal melanocytes. These findings suggest that CTLA-4 antibody blockade increases tumor immunity in some previously vaccinated cancer patients. PMID:12682289

  5. A TaqMan reverse transcription polymerase chain reaction (RT-PCR) in vitro potency assay for plasmid-based vaccine products.

    PubMed

    Mahajan, Rohit; Feher, Beth; Jones, Basil; Jones, Doug; Marjerison, Lana; Sam, Mindy; Hartikka, Jukka; Wloch, Mary; Lalor, Peggy; Kaslow, David; Hall, Keith; Rolland, Alain

    2008-09-01

    A TaqMan-based reverse transcription polymerase chain reaction (RT-PCR) assay has been developed as an in vitro potency assay to measure the most immediate biological activity of plasmid DNA (pDNA)-based products. The assay measures transgene-specific messenger RNA (mRNA) from cultured cells transfected with VCL-CB01, a bivalent pDNA-based human cytomegalovirus (CMV) vaccine. The forward and reverse primers have been designed to make the RT-PCR reaction selective for plasmid-derived mRNA and to allow discrimination of expression levels of individual plasmids in a multivalent pDNA vaccine. The relative potency of a vaccine lot is assessed by transfecting reference and test samples into cultured cells in parallel and analyzing total RNA from the cells by RT-PCR. Statistical analysis of dose response data from reference material supports a parallel-line model for calculating relative potency. Preliminary data demonstrate the ability of this assay to distinguish product potencies at 50, 75, 150, and 200% of the reference material. In addition, forced degradation of pDNA demonstrates that a decrease in relative potency as measured by the RT-PCR assay in vitro correlates well with a decrease in CMV DNA vaccine-mediated humoral immune responses in mice injected with the same material. PMID:18365771

  6. Production of a recombinant vaccine candidate against Burkholderia pseudomallei exploiting the bacterial N-glycosylation machinery

    PubMed Central

    Garcia-Quintanilla, Fatima; Iwashkiw, Jeremy A.; Price, Nancy L.; Stratilo, Chad; Feldman, Mario F.

    2014-01-01

    Vaccines developing immune responses toward surface carbohydrates conjugated to proteins are effective in preventing infection and death by bacterial pathogens. Traditional production of these vaccines utilizes complex synthetic chemistry to acquire and conjugate the glycan to a protein. However, glycoproteins produced by bacterial protein glycosylation systems are significantly easier to produce, and could possible be used as vaccine candidates. In this work, we functionally expressed the Burkholderia pseudomallei O polysaccharide (OPS II), the Campylobacter jejuni oligosaccharyltransferase (OTase), and a suitable glycoprotein (AcrA) in a designer E. coli strain with a higher efficiency for production of glycoconjugates. We were able to produce and purify the OPS II-AcrA glycoconjugate, and MS analysis confirmed correct glycan was produced and attached. We observed the attachment of the O-acetylated deoxyhexose directly to the acceptor protein, which expands the range of substrates utilized by the OTase PglB. Injection of the glycoprotein into mice generated an IgG immune response against B. pseudomallei, and this response was partially protective against an intranasal challenge. Our experiments show that bacterial engineered glycoconjugates can be utilized as vaccine candidates against B. pseudomallei. Additionally, our new E. coli strain SDB1 is more efficient in glycoprotein production, and could have additional applications in the future. PMID:25120536

  7. A pre-S/S CHO-derived hepatitis B virus vaccine protects woodchucks from WHV productive infection.

    PubMed

    Argentini, Claudio; Giuseppetti, Roberto; D'Ugo, Emilio; La Sorsa, Valentina; Tritarelli, Elena; Orobello, Sara; Canitano, Andrea; Glück, Reinhard; Rapicetta, Maria

    2005-05-25

    We evaluated whether a non-adjuvanted vaccine derived from Chinese hamster ovary cells was capable of providing protection against woodchuck hepatitis virus (WHV). Three woodchucks were vaccinated with four 50-microg doses and challenged with a previously characterized virus isolate (WHV197). In all three animals, titre levels of antibodies against hepatitis B surface antigens (anti-HBs) exceeded 10 mIU/ml, peaking at 150 mIU/ml. Challenge resulted in productive acute infection in the two non-vaccinated woodchucks yet in none of the vaccinated woodchucks. In the vaccinated animals, there was evidence of abortive infection. The results demonstrate that a human vaccine is able to protect woodchucks from WHV infection. PMID:15882525

  8. Setting up a platform for plant-based influenza virus vaccine production in South Africa

    PubMed Central

    2012-01-01

    Background During a global influenza pandemic, the vaccine requirements of developing countries can surpass their supply capabilities, if these exist at all, compelling them to rely on developed countries for stocks that may not be available in time. There is thus a need for developing countries in general to produce their own pandemic and possibly seasonal influenza vaccines. Here we describe the development of a plant-based platform for producing influenza vaccines locally, in South Africa. Plant-produced influenza vaccine candidates are quicker to develop and potentially cheaper than egg-produced influenza vaccines, and their production can be rapidly upscaled. In this study, we investigated the feasibility of producing a vaccine to the highly pathogenic avian influenza A subtype H5N1 virus, the most generally virulent influenza virus identified to date. Two variants of the haemagglutinin (HA) surface glycoprotein gene were synthesised for optimum expression in plants: these were the full-length HA gene (H5) and a truncated form lacking the transmembrane domain (H5tr). The genes were cloned into a panel of Agrobacterium tumefaciens binary plant expression vectors in order to test HA accumulation in different cell compartments. The constructs were transiently expressed in tobacco by means of agroinfiltration. Stable transgenic tobacco plants were also generated to provide seed for stable storage of the material as a pre-pandemic strategy. Results For both transient and transgenic expression systems the highest accumulation of full-length H5 protein occurred in the apoplastic spaces, while the highest accumulation of H5tr was in the endoplasmic reticulum. The H5 proteins were produced at relatively high concentrations in both systems. Following partial purification, haemagglutination and haemagglutination inhibition tests indicated that the conformation of the plant-produced HA variants was correct and the proteins were functional. The immunisation of chickens and mice with the candidate vaccines elicited HA-specific antibody responses. Conclusions We managed, after synthesis of two versions of a single gene, to produce by transient and transgenic expression in plants, two variants of a highly pathogenic avian influenza virus HA protein which could have vaccine potential. This is a proof of principle of the potential of plant-produced influenza vaccines as a feasible pandemic response strategy for South Africa and other developing countries. PMID:22536810

  9. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

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

  10. The use of smallpox virus as a biological weapon: the vaccination situation in France.

    PubMed

    Lévy-Bruhl, D; Guérin, N

    2001-11-01

    In the context of its plan to fight against bioterrorism, the Ministry of Health asked the Institut de Veille Sanitaire to evaluate the epidemic risk from a release of the small pox virus, and to make recommendations on potential vaccination strategies to be implemented. A benefit/risk assessment of various vaccination scenarios, including vaccination of the whole French population, was carried out to evaluate the severity of a terrorist action threat. This analysis concludes that at this stage, vaccination action does not seem to be justified. Even in the case of a real threat, the vaccination of frontline healthcare personnel, and in particular of contacts of cases, must be given priority. PMID:11891388

  11. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1...

  12. Packet vaccine: black-box exploit detection and signature generation

    Microsoft Academic Search

    Xiaofeng Wang; Zhuowei Li; Jun Xu; Michael K. Reiter; Chongkyung Kil; Jong Youl Choi

    2006-01-01

    In biology, a vaccine is a weakened strain of a virus or bac- terium that is intentionally injected into the body for the purpose of stimulating antibody production. Inspired by this idea, we propose a packet vaccine mechanism that ran- domizes address-like strings in packet payloads to carry out fast exploit detection, vulnerability diagnosis and signature generation. An exploit with

  13. The feasibility of a novel bioreactor for vaccine production of classical swine fever virus.

    PubMed

    Wu, Sheng-Chi; Liau, Ming-Yi; Lin, Ya-Ching; Sun, Chong-Jun; Wang, Chi-Ting

    2013-01-30

    The performance of a new type of tide mode culture system was investigated in this study. This novel bioreactor provides two separated stages, liquid and gas, for cell growth requirements. The immobilized cells absorbed the nutrient from medium during the liquid stage and subsequently were exposed directly to fresh air to absorb oxygen during the gas stage. Operating with PK15 cells under optimal conditions, we obtained 2.3×10(9) cells in 500ml reactor. It is 30 times higher than the initial inoculum and about 11 times higher than the production by roller bottle. For the vaccine production of classical swine fever (CSFV), a high virus titer of 2.1×10(9) median tissue culture infective dose (TCID(50)) was yielded which provided exceed 300 doses per milliliter of CSFV solution. Therefore, this new cultural system performed well not only for cell production but also for virus yield. It should be a highly efficient production for the CSFV vaccine and have practical potential in other animal cell culture vaccine. PMID:23261041

  14. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-12-01

    Due to the abundant supply of coal in the United States, significant research efforts have occurred over the past 15 years concerning the conversion of coal to liquid fuels. Researchers at the University of Arkansas have concentrated on a biological approach to coal liquefaction, starting with coal-derived synthesis gas as the raw material. Synthesis gas, a mixture of CO, H[sub 2], CO[sub 2], CH[sub 4] and sulfur gases, is first produced using traditional gasification techniques. The CO, CO[sub 2] and H[sub 2] are then converted to ethanol using a bacterial culture of Clostridium 1jungdahlii. Ethanol is the desired product if the resultant product stream is to be used as a liquid fuel. However, under normal operating conditions, the wild strain'' produces acetate in favor of ethanol in conjunction with growth in a 20:1 molar ratio. Research was performed to determine the conditions necessary to maximize not only the ratio of ethanol to acetate, but also to maximize the concentration of ethanol resulting in the product stream.

  15. Effect of selenium and vitamin E on antibody production by dairy cows vaccinated against Escherichia coli.

    PubMed

    Panousis, N; Roubies, N; Karatzias, H; Frydas, S; Papasteriadis, A

    2001-11-24

    Sixty clinically healthy Holstein cows were randomly assigned to one of four groups according to their age and parity and vaccinated in late pregnancy (day 190) with a multivalent vaccine against Escherichia coli. The 15 cows in the first group (SeE) were injected intramuscularly with a solution of sodium selenite (0.1 mg Se/kg bodyweight) and vitamin E (alpha-tocopherol acetate, 8 U/kg bodyweight), the cows in the second group (Se) received only selenium and the cows in the third group (E) received only vitamin E at the same doses and by the same route of administration; the cows in the fourth group were used as controls. The vaccination and the injections of selenium and vitamin E were repeated 42 days later. The concentration of selenium in whole blood and of vitamin E in serum was determined by fluorometric methods. Specific antibody titres against E coli were determined in serum samples by ELISA. The results showed that the injection of selenium either alone or in combination with vitamin E significantly improved the production of specific antibodies against E coli, and that the production of specific antibodies was greater after the administration of selenium alone. PMID:11764325

  16. Production of a conjugate vaccine for Salmonella enterica serovar Typhi from Citrobacter Vi.

    PubMed

    Micoli, F; Rondini, S; Pisoni, I; Giannelli, C; Di Cioccio, V; Costantino, P; Saul, A; Martin, L B

    2012-01-20

    A conjugate vaccine for Salmonella enterica serovar Typhi was produced by chemically linking Vi, purified from Citrobacter, to the non-toxic mutant diphtheria toxin CRM(197) via an adipic dihydrazide spacer using N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide coupling chemistry. The polysaccharide purification process was developed based on Vi precipitation from culture supernatant with cetyl trimethylammonium bromide (CTAB), solubilization of the CTA-polysaccharide salt with ethanol followed by exchange of the CTA(+) counter ion with Na(+). The purified Vi polysaccharide was fully O-acetylated and with high purity. The conjugation process was optimized to obtain a scalable process that has been used for GMP production at pilot scale of vaccine currently in clinical trials. PMID:22172503

  17. Coccidiosis in poultry: anticoccidial products, vaccines and other prevention strategies

    Microsoft Academic Search

    H. W. Peek; W. J. M. Landman

    2011-01-01

    Coccidiosis in chickens is a parasitic disease with great economic significance, which has been controlled successfully for decades using mainly anticoccidial products. However, large-scale and long-term use of anticoccidial drugs has led to the worldwide development of resistance against all these drugs. In order to minimize the occurrence of resistance, the rotation of various anticoccidial drugs in single and\\/or shuttle

  18. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL PRODUCTS USED IN DEPARTMENT PROGRAMS OR UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1...

  19. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL PRODUCTS USED IN DEPARTMENT PROGRAMS OR UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1...

  20. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL PRODUCTS USED IN DEPARTMENT PROGRAMS OR UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1...

  1. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.6 Packaging biological products. (a) Each multiple-dose final...

  2. Key Facts about Seasonal Flu Vaccine

    MedlinePLUS

    ... Safety . Â Top of Page Vaccine Supply and Distribution How much vaccine will be available during 2014- ... and distributors take a phased approach to vaccine distribution? Influenza vaccine production begins as early as 6 ...

  3. Effect of vaccination against Mycoplasma hyopneumoniae in pig herds with an all-in\\/all-out production system

    Microsoft Academic Search

    D Maes; H Deluyker; M Verdonck; F Castryck; C Miry; B Vrijens; W Verbeke; J Viaene; A de Kruif

    1999-01-01

    A multi-site field study was conducted to evaluate an inactivated Mycoplasma hyopneumoniae (Mh) vaccine in 14 pig herds infected by Mh and practising an all-in\\/all-out production system. In each herd, a vaccinated and control group of 250 pigs each were compared during the growing\\/finishing period with respect to performance parameters (major variables) and by means of clinical, serological and pathological

  4. Production and Efficacy of Peste Des Petits Ruminants Vaccine 75\\/1 in the Kingdom of Saudi Arabia

    Microsoft Academic Search

    S. M. Rashwan; H. N. Al-Khalaf; M. I. Al-Hammad; A. H. Azab; M. H. Moustafa; A. Diallo

    2000-01-01

    Rashwan, S. M., Al-Khalaf, H. N., Al-Hammad, M. I., Azab, A. H., Moustafa, M. H. and Diallo, A. 2000. Production and efficacy of peste des petits ruminants vaccine 75\\/1 in the Kingdom of Saudi Arabia. J. Appl. Anim. Res., 8: 225–231.A freeze dried live attenuated vaccine against peste des petits ruminants (PPR) infection was prepared by growing an attenuated PPR

  5. Production and Characterization of Neutralizing Monoclonal Antibodies Against Haemagglutinin Protein of peste des petits ruminants (PPR) Vaccine Virus

    Microsoft Academic Search

    S. Saravanan; R. P. Singh; V. Balamurugan; P. Saravanan; A. Sen; B. Sahay; J. Sarkar

    2007-01-01

    Saravanan, S., Singh, R.P., Balamurugan, V., Saravanan, P., Sen, A., Sahay, B., Sarkar, J. and Singh, R.K. 2007. Production and characterization of neutralizing monoclonal antibodies against haemagglutinin protein of peste des petits ruminants (PPR) vaccine virus. J. Appl. Anim. Res., 32: 207–210.A set of nine Peste des petits ruminants (PPR) virus specific hybridoma clones were produced against PPR vaccine virus

  6. Vaccines in Dermatology.

    PubMed

    Shah, Mitali M; Shah, Aishani C; Mahajan, Rashmi S; Bilimoria, Freny E

    2015-01-01

    A vaccine is a biological preparation that improves immunity to a specific disease. More than two centuries have passed since the first successful vaccine for smallpox was developed. We've come a long way since. Today's vaccines are among the 21(st) century's most successful and cost-effective public health tools for preventing diseases. PMID:26120155

  7. Selenium and vitamin E effect on antibody production of sheep vaccinated against enzootic abortion (Chlamydia psittaci).

    PubMed

    Giadinis, N; Koptopoulos, G; Roubles, N; Siarkou, V; Papasteriades, A

    2000-03-01

    The effect of selenium (Se) and vitamin E (vit E) on antibody production of sheep vaccinated against Chlamydia psittaci (ovis) was investigated. Thirty-two sheep, one year old, seronegative to Chlamydia infection, vaccinated against enterotoxemia and dewormed were used. Injectable sodium selenite (0.1 mg/kg b.w.) was given twice to animals of the first group (gSe), with a three week interval. The sheep of the second group (gE) received 1 g vit E each orally, six times at weekly intervals. The animals of the third group (gSeE) were given Se and vit E in doses and routes of administration as in gSe and gE. The animals of the fourth group served as controls (gC) and injected normal saline. The first vaccination was made at the time that the second Se injection was given. Revaccination was made two weeks later. The experiment lasted 29 weeks. The results indicated that Se alone led to a significant increase of Chlamydia antibody response (P < 0.05), but not when it was given in combination with vit E. Animals that received vit E (gE) had much lower titres, just above of those of the controls. PMID:10670702

  8. Large scale production and downstream processing of a recombinant porcine parvovirus vaccine.

    PubMed

    Maranga, L; Rueda, P; Antonis, A F G; Vela, C; Langeveld, J P M; Casal, J I; Carrondo, M J T

    2002-06-01

    Porcine parvovirus (PPV) virus-like particles (VLPs) constitute a potential vaccine for prevention of parvovirus-induced reproductive failure in gilts. Here we report the development of a large scale (25 l) production process for PPV-VLPs with baculovirus-infected insect cells. A low multiplicity of infection (MOI) strategy was efficiently applied avoiding the use of an extra baculovirus expansion step. The optimal harvest time was defined at 120 h post-infection at the MOI used, with the cell concentration at infection being 1.5x10(6) cells/ml. An efficient purification scheme using centrifugation, precipitation and ultrafiltration/diafiltration as stepwise unit operations was developed. The global yield of the downstream process was 68%. Baculovirus inactivation with Triton X-100 was successfully integrated into the purification scheme without an increase in the number of process stages. Immunogenicity of the PPV-VLPs tested in guinea pigs was similar to highly purified reference material produced from cells cultured in the presence of serum-containing medium. These results indicate the feasibility of industrial scale production of PPV-VLPs in the baculovirus system, safety of the product, and the potency of the product for vaccine application. PMID:12073130

  9. Designing cell lines for viral vaccine production: Where do we stand?

    PubMed

    Genzel, Yvonne

    2015-05-01

    Established animal cells, such as Vero, Madin Darby canine kidney (MDCK) or chicken embryo fibroblasts (CEFs), are still the main cell lines used for viral vaccine production, although new "designer cells" have been available for some years. These designer cell lines were specifically developed as a cell substrate for one application and are well characterized. Later screening for other possible applications widened the product range. These cells grow in suspension in chemically defined media under controlled conditions and can be used for up to 100 passages. Scale-up is easier and current process options allow cultivation in disposable bioreactors at cell concentrations higher than 1×10(7) cells/mL. This review covers the limitations of established cell lines and discusses the requirements and screening options for new host cells. Currently available designer cells for viral vaccine production (PER.C6, CAP, AGE1.CR, EB66 cells), together with other new cell lines (PBS-1, QOR/2E11, SogE, MFF-8C1 cells) that were recently described as possible cell substrates are presented. Using current process knowledge and cell line development tools, future upstream processing could resemble today's Chinese hamster ovary (CHO) cell processes for monoclonal antibody production: small scale bioreactors (disposable) in perfusion or fed-batch mode with cell concentrations above 1×10(8) cells/mL. PMID:25903999

  10. An Interspecific Nicotiana Hybrid as a Useful and Cost-Effective Platform for Production of Animal Vaccines

    PubMed Central

    Ling, Huai-Yian; Edwards, Aaron M.; Gantier, Michael P.; DeBoer, Kathleen D.; Neale, Alan D.; Hamill, John D.; Walmsley, Amanda M.

    2012-01-01

    The use of transgenic plants to produce novel products has great biotechnological potential as the relatively inexpensive inputs of light, water, and nutrients are utilised in return for potentially valuable bioactive metabolites, diagnostic proteins and vaccines. Extensive research is ongoing in this area internationally with the aim of producing plant-made vaccines of importance for both animals and humans. Vaccine purification is generally regarded as being integral to the preparation of safe and effective vaccines for use in humans. However, the use of crude plant extracts for animal immunisation may enable plant-made vaccines to become a cost-effective and efficacious approach to safely immunise large numbers of farm animals against diseases such as avian influenza. Since the technology associated with genetic transformation and large-scale propagation is very well established in Nicotiana, the genus has attributes well-suited for the production of plant-made vaccines. However the presence of potentially toxic alkaloids in Nicotiana extracts impedes their use as crude vaccine preparations. In the current study we describe a Nicotiana tabacum and N. glauca hybrid that expresses the HA glycoprotein of influenza A in its leaves but does not synthesize alkaloids. We demonstrate that injection with crude leaf extracts from these interspecific hybrid plants is a safe and effective approach for immunising mice. Moreover, this antigen-producing alkaloid-free, transgenic interspecific hybrid is vigorous, with a high capacity for vegetative shoot regeneration after harvesting. These plants are easily propagated by vegetative cuttings and have the added benefit of not producing viable pollen, thus reducing potential problems associated with bio-containment. Hence, these Nicotiana hybrids provide an advantageous production platform for partially purified, plant-made vaccines which may be particularly well suited for use in veterinary immunization programs. PMID:22539991

  11. Old and New: Recent Innovations in Vaccine Biology and Skin T Cells

    Microsoft Academic Search

    Thomas S Kupper

    2012-01-01

    Memory is the hallmark of the adaptive immune system, and the observation that infectious diseases often lead to lifelong immunity in individuals who survive a first infection became the genesis for the development of vaccines. Immunization, which is the iatrogenic engineering of a protective memory immune response to a pathogen, became a standard part of medical care in the twentieth

  12. "Light" Tobacco Products Pose Heavy Health Risks

    MedlinePLUS

    ... Tobacco Products Vaccines, Blood & Biologics Articulos en Espanol “Light” Tobacco Products Pose Heavy Health Risks Search the ... Feed A federal law is restricting the words “light,” “low,” and “mild” from tobacco products now on ...

  13. Susceptibility of cell substrates to PrPSc infection and safety control measures related to biological and biotherapeutical products

    PubMed Central

    LeBrun, Matthew; Huang, Hongsheng

    2008-01-01

    Concerns over the potential for infectious prion proteins to contaminate human biologics and biotherapeutics have been raised from time to time. Transmission of the pathogenic form of prion protein (PrPSc) through veterinary vaccines has been observed, yet no human case through the use of vaccine products has been reported. However, iatrogenic transmissions of PrPSc in humans through blood components, tissues and growth hormone have been reported. These findings underscore the importance of reliable detection or diagnostic methods to prevent the transmission of prion diseases, given that the number of asymptomatic infected individuals remains unknown, the perceived incubation time for human prion diseases could be decades, and no cure of the diseases has been found yet. A variety of biochemical and molecular methods can selectively concentrate PrPSc to facilitate its detection in tissues and cells. Furthermore, some methods routinely used in the manufacturing process of biological products have been found to be effective in reducing PrPSc from the products. Questions remain unanswered as to the validation criteria of these methods, the minimal infectious dose of the PrPSc required to cause infection and the susceptibility of cells used in gene therapy or the manufacturing process of biological products to PrPSc infections. Here, we discuss some of these challenging issues. PMID:19164901

  14. Microbial production of virus-like particle vaccine protein at gram-per-litre levels.

    PubMed

    Liew, Mervyn W O; Rajendran, Aravindan; Middelberg, Anton P J

    2010-10-15

    This study demonstrates the feasibility of large-scale production of murine polyomavirus VP1 protein in recombinant Escherichia coli as pentamers which are able to subsequently self-assemble in vitro into virus-like particles (VLPs). High-cell-density pH-stat fed-batch cultivation was employed to produce glutathione-S-transferase (GST)-VP1 fusion protein in soluble form. The expression of recombinant VP1 was induced with IPTG at different cell optical densities (OD at 600 nm of 20, 60 or 100). GST-VP1 production was highest when the culture was induced at a cell density of OD 60, with volumetric yield reaching 4.38 gL?¹ in 31h, which we believe is the highest volumetric productivity for viral capsid protein reported to date. The induction cell density is shown to have a significant effect on the overall volumetric yield of recombinant VP1 and on final cell density, but not on VLP quality. VP1 yield was enhanced 15-fold by scaling-up from shake flask to pH-stat fed-batch cultivation in a bioreactor. Although numerous studies have expressed structural viral protein in E. coli, we believe this is the first report of translation to bioreactors yielding gram-per-litre levels. This VLP production technology overcomes major drawbacks associated with eukaryotic cell-based vaccine production technologies, and propounds the scope for large-scale commercially viable E. coli based VLP production by significantly reducing vaccine production time and cost. PMID:20797415

  15. Bacillus subtilis comes of age as a vaccine production host and delivery vehicle.

    PubMed

    Rosales-Mendoza, Sergio; Angulo, Carlos

    2015-08-01

    Bacillus subtilis is a vaccine production host and delivery vector with several advantages such as a low production cost, straightforward administration as it is safe for human consumption and the production of spores exerting adjuvant effects. This review summarizes the expression approaches and provides an updated outlook of how a myriad of pathogens have been targeted under this technology. Furthermore, by reviewing the literature, several promising candidates in terms of immunogenic and immunoprotective potential have been identified. The immune profiles achieved comprise either humoral or cellular responses, which reflect versatility for application in the fight of distinct pathologies that demand specific polarization on the immune responses. Some perspectives for this field are also envisioned. PMID:26028252

  16. Biologically based pest controls: Markets, industries, and products. Special report

    SciTech Connect

    Ridgway, R.L.; Inscoe, M.N.; Thorpe, K.W.

    1994-05-20

    Numbers and amounts of conventional pesticides to combat insect pests, weeds and plant diseases are likely to decline. Although biologically based pest control products have been touted as possible replacements, such products now comprise less than 2% of the market in the United States. Twelve large multinational companies market 80% of the world`s pesticides, valued at about $200 billion, and are responsible for about 20% of the activities to develop and/or produce biological products. In the U.S. about 65 small companies are responsible for 80% of the activities on biological products, which are valued at about $165 million. Without major changes in the research, development, and delivery system, biological products are not likely to be practical replacements for significant amounts of conventional pesticides in the foreseeable future.

  17. Biological characterization of clones derived from the edmonston strain of measles virus in comparison with schwarz and CAM70 vaccine strains

    Microsoft Academic Search

    Maria Beatriz Junqueira Borges; George F Mann; Marcos da Silva Freire

    1996-01-01

    Four virus clones were derived from the Edmonston strain of measles virus by repeated plaque purification. These clones were compared with the vaccine strains Schwarz and CAM-70 in terms of biological activities including plaque formation, hemagglutination, hemolysis and replication in Vero cells and chick embryo fibroblasts (CEF). Two clones of intermediate plaque yielded mixed plaque populations on subcultivation whereas the

  18. Lymphocytic vasculitis associated with the anthrax vaccine: case report and review of anthrax vaccination.

    PubMed

    Muñiz, Antonio E

    2003-10-01

    Anthrax is caused by the spore-forming bacteria Bacillus anthracis. It occurs naturally, but recently has been manufactured as a biological warfare agent. This makes prophylaxis for anthrax an urgent concern and efforts are ongoing for the production of an efficient and safe vaccine. Side effects to the current anthrax vaccine are usually minor and mainly consist of local skin reactions. Occasionally an unusual complication may occur; a case of a patient with lymphocytic vasculitis temporally associated with the anthrax vaccine is reported. PMID:14585454

  19. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...container of which bears a United States veterinary license number or a United States veterinary permit number or other mark required...distribution and sale of a serial or subserial of a veterinary biological product by the Secretary,...

  20. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...container of which bears a United States veterinary license number or a United States veterinary permit number or other mark required...distribution and sale of a serial or subserial of a veterinary biological product by the Secretary,...

  1. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...container of which bears a United States veterinary license number or a United States veterinary permit number or other mark required...distribution and sale of a serial or subserial of a veterinary biological product by the Secretary,...

  2. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...container of which bears a United States veterinary license number or a United States veterinary permit number or other mark required...distribution and sale of a serial or subserial of a veterinary biological product by the Secretary,...

  3. Neisseria proteomics for antigen discovery and vaccine development.

    PubMed

    Christodoulides, Myron

    2014-10-01

    Neisseria meningitidis (meningococcus) is a major causative organism of meningitis and sepsis and Neisseria gonorrhoeae (gonococcus) is the causative organism of the sexually transmitted disease gonorrhea. Infections caused by meningococci are vaccine-preventable, whereas gonococcal vaccine research and development has languished for decades and the correlates of protection are still largely unknown. In the past two decades, complementary 'omic' platforms have been developed to interrogate Neisseria genomes and gene products. Proteomic techniques applied to whole Neisseria bacteria, outer membranes and outer membrane vesicle vaccines have generated protein maps and also allowed the examination of environmental stresses on protein expression. In particular, immuno-proteomics has identified proteins whose expression is correlated with the development of human natural immunity to meningococcal infection and colonization and following vaccination. Neisseria proteomic techniques have produced a catalog of potential vaccine antigens and investigating the functional and biological properties of these proteins could finally provide 'universal' Neisseria vaccines. PMID:25017717

  4. Vaccines against malaria

    PubMed Central

    Hill, Adrian V. S.

    2011-01-01

    There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates. PMID:21893544

  5. BIOLOGICAL CONTROL OF PESTS IN LIVESTOCK PRODUCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Filth flies have a wide array of natural enemies that can be exploited for augmentative biological control. There are several important predators of fly eggs and larvae, including the mite Macrocheles muscaedomesticae, the histerid beetle Carcinops pumilio, and the black dump fly Hydrotaea aenescen...

  6. 75 FR 75682 - Reclassification of Category IIIA Biological Products, Bacterial Vaccines and Related Biological...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ...the Development of Skin Lesion in Mice after Inoculation with Herpes Simplex Virus'' (Department of Microbiology, School of...the Development of Skin Lesion in Mice after Inoculation with Herpes Simplex Virus,'' Department of Microbiology, School of...

  7. Salmonid alphavirus replication in mosquito cells: towards a novel vaccine production system

    PubMed Central

    Hikke, Mia C; Verest, Marjan; Vlak, Just M; Pijlman, Gorben P

    2014-01-01

    Salmonid alphavirus (SAV) causes pancreas disease and sleeping disease in Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) and confers a major burden to the aquaculture industry. A commercial inactivated whole virus vaccine propagated in a salmon cell line at low temperature provides effective protection against SAV infections. Alphaviruses (family Togaviridae) are generally transmitted between vertebrate hosts via blood-sucking arthropod vectors, typically mosquitoes. SAV is unique in this respect because it can be transmitted directly from fish to fish and has no known invertebrate vector. Here, we show for the first time that SAV is able to complete a full infectious cycle within arthropod cells derived from the Asian tiger mosquito Aedes albopictus. Progeny virus is produced in C6/36 and U4.4. cells in a temperature-dependent manner (at 15°C but not at 18°C), can be serially passaged and remains infectious to salmonid Chinook salmon embryo cells. This suggests that SAV is not a vertebrate-restricted alphavirus after all and may have the potential to replicate in invertebrates. The current study also shows the ability of SAV to be propagated in mosquito cells, thereby possibly providing an alternative SAV production system for vaccine applications. PMID:24418177

  8. [Towards a new vaccine economy?].

    PubMed

    Poirot, P; Martin, J F

    1994-01-01

    When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921683

  9. Identifying Recalled Products

    MedlinePLUS Videos and Cool Tools

    ... Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to ... Search FDA Submit search Popular Content Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics ...

  10. Regulatory science accelerates the development of biotechnology drugs and vaccines by NIFDC

    PubMed Central

    Liang, Zhenglun; Mao, Qunying; Wang, Yiping; Li, Changgui; Gao, Kai; Wang, Junzhi

    2014-01-01

    The Chinese National Institutes for Food and Drug Control (NIFDC) is the national laboratory responsible for the quality control of pharmaceutical products. In recent years, to ensure the quality of biological products and improve the research and development (R&D) of new biological drugs and vaccines, NIFDC conducted a series of regulatory science studies on key technologies for quality control and evaluation, and established a quality control and evaluation platform for biological drugs and vaccines. These studies accelerated the R&D of the biological drugs and vaccines in China and assured their safety and efficacy. In this paper, NIFDC's duties and achievements in the biological drug and vaccine field are summarized. PMID:26038758

  11. Use of polymerase chain reaction (PCR) for the detection of vaccine contamination by infectious laryngotracheitis virus

    Microsoft Academic Search

    Andrea Vögtlin; Lukas Bruckner; Hans-Peter Ottiger

    1999-01-01

    Quality control of biologicals for veterinary use includes certification of freedom from extraneous agents. Contamination of vaccines may originate from various materials used for production and during manufacturing process. Requirements for avian virus vaccines to demonstrate freedom of adventitious agents are stated in the European Pharmacopoeia and include monitoring for infectious laryngotracheitis virus (ILTV). ILTV is an avian herpesvirus belonging

  12. Biological and genetic properties of SA??-14-2, a live-attenuated Japanese encephalitis vaccine that is currently available for humans.

    PubMed

    Song, Byung-Hak; Yun, Gil-Nam; Kim, Jin-Kyoung; Yun, Sang-Im; Lee, Young-Min

    2012-08-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is a major cause of acute encephalitis, a disease of significance for global public health. In the absence of antiviral therapy to treat JEV infection, vaccination is the most effective method of preventing the disease. In JE-endemic areas, the most widely used vaccine to date is SA(14)-14-2, a live-attenuated virus derived from its virulent parent SA(14). In this study, we describe the biological properties of SA(14)-14-2, both in vitro and in vivo, and report the genetic characteristics of its genomic RNA. In BHK-21 (hamster kidney) cells, SA(14)-14-2 displayed a slight delay in plaque formation and growth kinetics when compared to a virulent JEV strain, CNU/LP2, with no decrease in maximum virus production. The delay in viral growth was also observed in two other cell lines, SH-SY5Y (human neuroblastoma) and C6/36 (mosquito larva), which are potentially relevant to JEV pathogenesis and transmission. In 3-week-old ICR mice, SA(14)-14-2 did not cause any symptoms or death after either intracerebral or peripheral inoculation with a maximum dose of up to 1.5×10(3) plaque-forming units (PFU) per mouse. The SA(14)-14-2 genome consisted of 10977 nucleotides, one nucleotide longer than all the previously reported genomes of SA(14)-14-2, SA(14) and two other SA(14)-derived attenuated viruses. This difference was due to an insertion of one G nucleotide at position 10701 in the 3 noncoding region. Also, we noted a significant number of nucleotide and/or amino acid substitutions throughout the genome of SA(14)-14-2, except for the prM protein-coding region, that differed from SA(14) and/or the other two attenuated viruses. Our results, together with others', provide a foundation not only for the study of JEV virulence but also for the development of new and improved vaccines for JEV. PMID:22923123

  13. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false U.S. Veterinary Biological Product License. 102...BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a...product shall be specified on a U.S. Veterinary Biological Product License,...

  14. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 2012-01-01 false U.S. Veterinary Biological Product License. 102...BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a...product shall be specified on a U.S. Veterinary Biological Product License,...

  15. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false U.S. Veterinary Biological Product License. 102...BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a...product shall be specified on a U.S. Veterinary Biological Product License,...

  16. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 2011-01-01 false U.S. Veterinary Biological Product License. 102...BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a...product shall be specified on a U.S. Veterinary Biological Product License,...

  17. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false U.S. Veterinary Biological Product License. 102...BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a...product shall be specified on a U.S. Veterinary Biological Product License,...

  18. Minimization of excess sludge production for biological wastewater treatment

    Microsoft Academic Search

    Yuansong Wei; Renze T. Van Houten; Arjan R. Borger; Dick H. Eikelboom; Yaobo Fan

    2003-01-01

    Excess sludge treatment and disposal currently represents a rising challenge for wastewater treatment plants (WWTPs) due to economic, environmental and regulation factors. There is therefore considerable impetus to explore and develop strategies and technologies for reducing excess sludge production in biological wastewater treatment processes. This paper reviews current strategies for reducing sludge production based on these mechanisms: lysis-cryptic growth, uncoupling

  19. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    A batch kinetic study involving Clostridium lungdahlii in a mineral medium was carried out in order to provide baseline data for the effects of nutrients on product ratio and kinetics. The use of this minimal medium containing vitamins, minerals, select amino acids and salts showed both a lower maximum specific growth rate and a lower maximum specific uptake rate than found when using a complex medium supplemented with 0.01% yeast extract. At the same time, the product ratio was improved slightly in favor of ethanol over acetate. Future experiments will measure the effects of ammonia and phosphate limitation on product ratio and process kinetics.

  20. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    Previous results have shown that the medium pH, the composition of the medium and concentration of medium constituents significantly affect the ratio of ethanol to acetate in the product stream when fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas to products by Clostridium ljungdahlii. An additional batch study was carried out varying the agitation rate at pH 4, 4.5 and 5.0. It was speculated that increased agitation rates in combination with low pH might result in increased ethanol production while, at the same time, yielding higher cell concentrations which could eventually result in higher ethanol concentrations.

  1. Production of biopharmaceuticals and vaccines in plants via the chloroplast genome.

    PubMed

    Daniell, Henry

    2006-10-01

    Transgenic plants offer many advantages, including low cost of production (by elimination of fermenters), storage and transportation; heat stability; and absence of human pathogens. When therapeutic proteins are orally delivered, plant cells protect antigens in the stomach through bioencapsulation and eliminate the need for expensive purification and sterile injections, in addition to development of both systemic and mucosal immunity. Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance and multi-gene expression in a single transformation event. Hyper-expression of vaccine antigens against cholera, tetanus, anthrax, plague or canine parvovirus (4-31% of total soluble protein, tsp) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato), as well as the availability of antibiotic-free selectable markers or the ability to excise selectable marker genes, facilitate oral delivery. Hyper-expression of several therapeutic proteins, including human serum albumin (11.1% tsp), somatotropin (7% tsp), interferon-gamma (6% tsp), anti-microbial peptide (21.5% tsp), facilitates efficient and economic purification. Also, the presence of chaperones and enzymes in chloroplasts facilitate assembly of complex multi-subunit proteins and correct folding of human blood proteins with proper disulfide bonds. Functionality of chloroplast-derived vaccine antigens and therapeutic proteins has been demonstrated by several assays, including the macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLa cells or human lung carcinoma cells against encephalomyocarditis virus, systemic immune response, protection against pathogen challenge, and growth or inhibition of cell cultures. Thus, transgenic chloroplasts are ideal bioreactors for production of functional human and animal therapeutic proteins in an environmentally friendly manner. PMID:17004305

  2. Biological production of ethanol fom coal

    SciTech Connect

    Not Available

    1992-05-01

    Research is continuing in an attempt to increase both the ethanol concentration and product ratio using C. ljungdahlii. The purpose of this report is to present data (acetate to ethanol) utilizing a medium prepared especially for C. ljungdahlii. Medium development studies are presented, as well as reactor studies with the new medium in batch reactors. Continuous stirred tank reactor (CSTR) with cell recycle. The use of this new medium has resulted in significant improvements in cell concentration, ethanol concentration and product ratio.

  3. DNA vaccines: ready for prime time?

    PubMed Central

    Kutzler, Michele A.; Weiner, David B.

    2015-01-01

    Since the discovery, over a decade and a half ago, that genetically engineered DNA can be delivered in vaccine form and elicit an immune response, there has been much progress in understanding the basic biology of this platform. A large amount of data has been generated in preclinical model systems, and more sustained cellular responses and more consistent antibody responses are being observed in the clinic. Four DNA vaccine products have recently been approved, all in the area of veterinary medicine. These results suggest a productive future for this technology as more optimized constructs, better trial designs and improved platforms are being brought into the clinic. PMID:18781156

  4. Detection of endotoxin in biological products by the limulus test.

    PubMed

    Cooper, J F; Pearson, S M

    1977-01-01

    The limulus amebocyte lysate (LAL) test is established as a beneficial quality assurance measure for the parenteral drug industry because of its sensitivity, specificity, and simplicity. Limulus amebocyte lysate reacts with various forms of endotoxin to form an opaque gel under acceptable conditions of pH, temperature, and ionic content. Although certain materials and conditions may alter the lysate-endotoxin reaction, the test is not significantly limited by inhibition or non-specific activation. Many U.S. drug firms apply the LAL test generally for monitoring production water and other ingredients, for an in-process control, and as a supplemental end product test for pyrogenic contamination. Specific applications are made for bacterial and viral vaccines, antineoplastic agents, radiopharmaceuticals and drugs designed for intrathecal injection. Efforts to standardize LAL test technique and lysate potency continue. PMID:838151

  5. Establishment of Canine RNA Polymerase I-Driven Reverse Genetics for Influenza A Virus: Its Application for H5N1 Vaccine Production

    Microsoft Academic Search

    Shin Murakami; Taisuke Horimoto; Shinya Yamada; Satoshi Kakugawa; Hideo Goto; Yoshihiro Kawaoka

    2008-01-01

    In the event of a new influenza pandemic, vaccines whose antigenicities match those of circulating strains must be rapidly produced. Here, we established an alternative reverse genetics system for influenza virus using the canine polymerase I (PolI) promoter sequence that works efficiently in the Madin-Darby canine kidney cell line, a cell line approved for human vaccine production. Using this system,

  6. Effect of biological pretreatments in enhancing corn straw biogas production

    Microsoft Academic Search

    Weizhang Zhong; Zhongzhi Zhang; Yijing Luo; Shanshan Sun; Wei Qiao; Meng Xiao

    2011-01-01

    A biological pretreatment with new complex microbial agents was used to pretreat corn straw at ambient temperature (about 20°C) to improve its biodegradability and anaerobic biogas production. A complex microbial agent dose of 0.01% (w\\/w) and pretreatment time of 15days were appropriate for biological pretreatment. These treatment conditions resulted in 33.07% more total biogas yield, 75.57% more methane yield, and

  7. Physical Transport of Nutrients and the Maintenance of Biological Production

    Microsoft Academic Search

    Richard G. Williams; Michael J. Follows

    \\u000a The oceanic distributions of nutrients and patterns of biological production are controlled by the interplay of biogeochemical\\u000a and physical processes, and external sources. Biological and chemical processes lead to the transformation of nutrients between\\u000a inorganic and organic forms, and also between dissolved and particulate forms. Physical processes redistribute nutrients within\\u000a the water column through transport and mixing. The combined role

  8. Vaccines against poverty

    PubMed Central

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  9. Proliferative and T-cell specific interleukin (IL-2/IL-4) production responses in spleen cells from mice vaccinated with aroA live attenuated Salmonella vaccines.

    PubMed

    Villarreal, B; Mastroeni, P; de Hormaeche, R D; Hormaeche, C E

    1992-10-01

    T-cell responses were studied in mice immunized with the Salmonella typhimurium aroA SL3261 live attenuated vaccine strain. T-cell responses in the spleen, both in whole cell populations and in nylon wool non-adherent (T-cell enriched) cells, were studied in vitro as proliferation by incorporation of tritiated thymidine and production of T-cell specific cytokines [IL-2 (interleukin-2)/IL-4]. Stimulating antigens included whole Salmonella lysates and purified lipopolysaccharide (LPS), both untreated and after alkaline hydrolysis to prevent the non-specific mitogenic effect of LPS. Strong proliferative responses were obtained with untreated whole cell extract and LPS, which were decreased by polymyxin B (PB). Alkaline detoxification of the antigens decreased the proliferative response of nylon-wool non-adherent populations to LPS, but greatly increased their response to the Salmonella extract. Surprisingly, PB also reduced proliferation to detoxified LPS. Little or no IL-2/IL-4 production was seen in response to LPS or purified polysaccharide antigens, while there was a strong IL-2/IL-4 response to whole cell lysate, again markedly increasing after alkaline treatment. The results suggest that the T-cell response elicited by immunization with live Salmonella aroA vaccines in mice recognizes antigens other than LPS determinants, and that estimation of T-cell responses to Salmonella antigens by proliferation alone may yield misleading results. PMID:1298869

  10. Yeast synthetic biology toolbox and applications for biofuel production.

    PubMed

    Tsai, Ching-Sung; Kwak, Suryang; Turner, Timothy L; Jin, Yong-Su

    2014-09-01

    Yeasts are efficient biofuel producers with numerous advantages outcompeting bacterial counterparts. While most synthetic biology tools have been developed and customized for bacteria especially for Escherichia coli, yeast synthetic biological tools have been exploited for improving yeast to produce fuels and chemicals from renewable biomass. Here we review the current status of synthetic biological tools and their applications for biofuel production, focusing on the model strain Saccharomyces cerevisiae. We describe assembly techniques that have been developed for constructing genes, pathways, and genomes in yeast. Moreover, we discuss synthetic parts for allowing precise control of gene expression at both transcriptional and translational levels. Applications of these synthetic biological approaches have led to identification of effective gene targets that are responsible for desirable traits, such as cellulosic sugar utilization, advanced biofuel production, and enhanced tolerance against toxic products for biofuel production from renewable biomass. Although an array of synthetic biology tools and devices are available, we observed some gaps existing in tool development to achieve industrial utilization. Looking forward, future tool development should focus on industrial cultivation conditions utilizing industrial strains. PMID:25195615

  11. Production and stabilization of the trimeric influenza hemagglutinin stem domain for potentially broadly protective influenza vaccines.

    PubMed

    Lu, Yuan; Welsh, John P; Swartz, James R

    2014-01-01

    The rapid dissemination of the 2009 pandemic H1N1 influenza virus emphasizes the need for universal influenza vaccines that would broadly protect against multiple mutated strains. Recent efforts have focused on the highly conserved hemagglutinin (HA) stem domain, which must undergo a significant conformational change for effective viral infection. Although the production of isolated domains of multimeric ectodomain proteins has proven difficult, we report a method to rapidly produce the properly folded HA stem domain protein from influenza virus A/California/05/2009 (H1N1) by using Escherichia coli-based cell-free protein synthesis and a simple refolding protocol. The T4 bacteriophage fibritin foldon placed at the C terminus of the HA stem domain induces trimer formation. Placing emphasis on newly exposed protein surfaces, several hydrophobic residues were mutated, two polypeptide segments were deleted, and the number of disulfide bonds in each monomer was reduced from four to two. High pH and Brij 35 detergent emerged as the most beneficial factors for improving the refolding yield. To stabilize the trimer of the HA stem-foldon fusion, new intermolecular disulfide bonds were finally introduced between foldon monomers and between stem domain monomers. The correct immunogenic conformation of the stabilized HA stem domain trimer was confirmed by using antibodies CR6261, C179, and FI6 that block influenza infection by binding to the HA stem domain trimer. These results suggest great promise for a broadly protective vaccine and also demonstrate a unique approach for producing individual domains of complex multimeric proteins. PMID:24344259

  12. WHO Expert Committee on biological standardization.

    PubMed

    2011-01-01

    This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international recommendations for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the attention of the Committee and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, and endocrinological substances. The second part of the report, of particular relevance to manufacturers and national regulatory authorities, contains WHO recommendations and guidelines on Japanese encephalitis vaccine (inactivated), human; regulatory preparedness for human pandemic influenza vaccines; and clinical evaluation of meningococcal C conjugate vaccines. Also included are a list of recommendations, guidelines and other documents for biological substances used in medicine, and of international standards and reference reagent for biological substances. PMID:22420130

  13. Biological production of liquid fuels from biomass

    SciTech Connect

    none,

    1982-01-01

    A scheme for the production of liquid fuels from renewable resources such as poplar wood and lignocellulosic wastes from a refuse hydropulper was investigated. The particular scheme being studied involves the conversion of a cellulosic residue, resulting from a solvent delignified lignocellulosic feed, into either high concentration sugar syrups or into ethyl and/or butyl alcohol. The construction of a pilot apparatus for solvent delignifying 150 g samples of lignocellulosic feeds was completed. Also, an analysis method for characterizing the delignified product has been selected and tested. This is a method recommended in the Forage Fiber Handbook. Delignified samples are now being prepared and tested for their extent of delignification and susceptibility to enzyme hydrolysis. Work is continuing on characterizing the cellulase and cellobiase enzyme systems derived from the YX strain of Thermomonospora.

  14. Biological treatment of shrimp production wastewater

    Microsoft Academic Search

    Raj Boopathy

    2009-01-01

    Over the last few decades, there has been an increase in consumer demand for shrimp, which has resulted in its worldwide aquaculture\\u000a production. In the United States, the stringent enforcement of environmental regulations encourages shrimp farmers to develop\\u000a new technologies, such as recirculating raceway systems. This is a zero-water exchange system capable of producing high-density\\u000a shrimp yields. The system also

  15. Why are pharmaceutical companies gradually abandoning vaccines?

    PubMed

    Offit, Paul A

    2005-01-01

    During the past fifty years, the number of pharmaceutical companies making vaccines has decreased dramatically, and those that still make vaccines have reduced resources to make new ones. Pharmaceutical companies are gradually abandoning vaccines because the research, development, testing, and manufacture of vaccines are expensive and because the market to sell vaccines is much smaller than the market for other drug products. Congressional action could assure both a steady supply of existing vaccines and the promise of vaccines for the future. PMID:15886152

  16. The Biology of Avian Eimeria with an Emphasis on their Control by Vaccination

    Microsoft Academic Search

    Martin W. Shirley; Adrian L. Smith; Fiona M. Tomley

    2005-01-01

    Studies on the biology of the avian species of Eimeria are currently benefiting from the availability of a comprehensive sequence for the nuclear genome of Eimeria tenella. Allied to some recent advances in transgenic technologies and genetic approaches to identify protective antigens, some elements are now being assembled that should be helpful for the development of a new generation of

  17. Neurotrophic Natural Products: Chemistry and Biology

    PubMed Central

    Xu, Jing; Lacoske, Michelle H.

    2014-01-01

    Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project. PMID:24353244

  18. Smallpox: a review of clinical disease and vaccination.

    PubMed

    Lofquist, Jennifer M; Weimert, Nicole A; Hayney, Mary S

    2003-04-15

    The clinical course of smallpox infection and the current and future roles of vaccination and strategies for controlling smallpox outbreaks are reviewed. Close personal contact is required for transmission of variola, the DNA virus that causes smallpox. Following an incubation period, infected persons have prodromal symptoms that include high fever, back pain, malaise, and prostration. The eruptive stage is characterized by maculopapular rash that progresses to papules, then vesicles, and then pustules and scab lesions. The mortality rate for smallpox is approximately 30%. Patients having a fever and rash may be confused with having chickenpox. The most effective method for preventing smallpox epidemic progression is vaccination. Until recently, only 15 million doses of smallpox vaccine--manufactured 20 years ago--were available in the United States. The vaccine is a live vaccinia virus preparation administered by scarification with a bifurcated needle. The immune response is protective against orthopoxviruses, including variola. Vaccination is associated with moderate to severe complications, such as generalized vaccinia, eczema vaccinatum, progressive vaccinia, and postvaccinial encephalitis. Efforts for vaccine production are now focused on a live cell-culture-derived vaccinia virus vaccine. Although smallpox was eradicated in 1980, it remains a potential agent for bioterrorism. As a category A biological weapon, its potential to devastate populations causes concern among those in the public health community who have been actively developing plants to deal with smallpox and other potential agents of biological warfare. The only proven effective strategy against smallpox is vaccination. PMID:12749161

  19. The Structural Biology of Enzymes Involved in Natural Product Glycosylation

    PubMed Central

    Singh, Shanteri; Phillips, George N.

    2012-01-01

    The glycosylation of microbial natural products often dramatically influences the biological and/or pharmacological activities of the parental metabolite. Over the past decade, crystal structures of several enzymes involved in the biosynthesis and attachment of novel sugars found appended to natural products have emerged. In many cases, these studies have paved the way to a better understanding of the corresponding enzyme mechanism of action and have served as a starting point for engineering variant enzymes to facilitate to production of differentially-glycosylated natural products. This review specifically summarizes the structural studies of bacterial enzymes involved in biosynthesis of novel sugar nucleotides. PMID:22688446

  20. Differences of circulating Bordetella pertussis population in Argentina from the strain used in vaccine production

    Microsoft Academic Search

    M Fingermann; J Fernández; F Sisti; M E Rodríguez; B Gatti; D Bottero; A Graieb; M E Gaillard; S González Ayala; F R Mooi; H Lopardo; D Hozbor

    2007-01-01

    In Argentina, as in other countries, the number of pertussis cases has been increasing, even in highly vaccinated zones. Many reports suggest that the decline of vaccine efficacy due to antigenic shifts in the circulating Bordetella pertussis might be among the factors that contribute to pertussis re-emergence in different parts of the world. To evaluate the incidence of this factor

  1. Pilot-Scale Production and Characterization of Paramyosin, a Vaccine Candidate for Schistosomiasis Japonica

    Microsoft Academic Search

    Mario Jiz; Hai-Wei Wu; Rui Meng; Sunthorn Pond-Tor; Mindy Reynolds; Jennifer F. Friedman; Remigio Olveda; Luz Acosta; Jonathan D. Kurtis

    2008-01-01

    Despite effective chemotherapy, schistosomiasis remains a major public health problem in the developing world, with at least 200 million active infections resulting in significant morbidity. Rapid reinfection after treatment, accompanied by extensive residual morbidity, mandates alternative control strategies, including vaccine development. Paramyosin, a myofibrillar protein found only in invertebrates, has been widely studied as a vaccine candidate for both Schistosoma

  2. Anthrax vaccination strategies

    Microsoft Academic Search

    Robert J. Cybulski Jr.; Patrick Sanz; Alison D. O’Brien

    2009-01-01

    The biological attack conducted through the US postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and

  3. PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    EPA Science Inventory

    PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS Miroslav Styblo1,2,*, Zuzana Drobna1, Felecia S. Walton1, Ilona Jaspers1,2, Shan Lin3, Stephen B. Waters3, David J. Thomas4 1Department of Pediatrics, 2Center for Environmental Medicine an...

  4. Biology and management of psocids infesting stored products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously regarded as minor nuisance pests, psocids belonging to the genus Liposcelis are now a major problem for effective protection of stored-products world-wide. In this review we examine the apparent biological and operational reasons behind this phenomenon and why conventional pest management...

  5. Volatilization and Efflux of Mercury from Biologically Productive Ocean Regions

    Microsoft Academic Search

    Jonathan Philip Kim

    1987-01-01

    Mercury volatilization and oceanic evasion to the atmosphere were investigated in the tropical Pacific Ocean with emphasis on the biologically productive equatorial region. Further studies were conducted at two stations in the oligiotrophic North Pacific gyre, and in the estuarine mesocosms at the Marine Ecosystems Research Laboratory (MERL), University of Rhode Island. Dissolved gaseous Hg (DGM) in the tropical Pacific

  6. Natural products with health benefits from marine biological resources

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ocean is the cradle of lives, which provides a diverse array of intriguing natural products that has captured scientists’ attention in the past few decades due to their significant and extremely potent biological activities. In addition to being rich sources for pharmaceutical drugs, marine nat...

  7. Adventitious agents in viral vaccines: lessons learned from 4 case studies.

    PubMed

    Petricciani, John; Sheets, Rebecca; Griffiths, Elwyn; Knezevic, Ivana

    2014-09-01

    Since the earliest days of biological product manufacture, there have been a number of instances where laboratory studies provided evidence for the presence of adventitious agents in a marketed product. Lessons learned from such events can be used to strengthen regulatory preparedness for the future. We have therefore selected four instances where an adventitious agent, or a signal suggesting the presence of an agent, was found in a viral vaccine, and have developed a case study for each. The four cases are: a) SV40 in polio vaccines; b) bacteriophage in measles and polio vaccines; c) reverse transcriptase in measles and mumps vaccines; and d) porcine circovirus and porcine circovirus DNA sequences in rotavirus vaccines. The lessons learned from each event are discussed. Based in part on those experiences, certain scientific principles have been identified by WHO that should be considered in regulatory risk evaluation if an adventitious agent is found in a marketed vaccine in the future. PMID:25135887

  8. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    SciTech Connect

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People's Republic of China (China)] [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People's Republic of China (China); Wang, Yue, E-mail: euy-tokyo@umin.ac.jp [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People's Republic of China (China)] [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People's Republic of China (China); Liao, Guoyang, E-mail: liaogy@21cn.com [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People's Republic of China (China)] [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People's Republic of China (China)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  9. Novel vaccination approaches against equine alphavirus encephalitides.

    PubMed

    Carossino, Mariano; Thiry, Etienne; de la Grandière, Ana; Barrandeguy, Maria E

    2014-01-01

    The current production of inactivated vaccines for the prevention of equine alphavirus encephalitides caused by Eastern, Western and Venezuelan Equine Encephalitis viruses (EEEV, WEEV, VEEV) involves the manipulation of large quantities of infectious viral particles under biosafety level 3 containment laboratories with the potential risk of transmission to the operators. Moreover, these vaccines are not capable of inducing a long-lasting immunity. Modified live vaccines, which were also attempted, maintain residual virulence and neurotropism, causing disease in both horses and humans. Therefore, the production of an efficacious second generation vaccine which could be used in the prevention of alphavirus infection without the need to manipulate infectious viral particles under high biocontainment conditions could be of great benefit for the worldwide horse industry. Furthermore, equine alphaviruses are considered as biological threat agents. Subunit, chimeric, gene-deleted live mutants, DNA and adenovirus-vectored alphavirus vaccines have been evaluated; such approaches are reviewed in this work. Climate changes, together with modifications in bird and vector ecology, are leading to the arise of emerging pathogens in new geographical locations, and these zoonotic New World arboviruses are gaining concern. Novel vaccine development does show a promising future for prevention of these infections in both horses and humans. PMID:24295803

  10. The Interstellar Production of Biologically Important Organics

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; Bernstein, Max P.; Dworkin, Jason; Allamandola, Louis J.

    2000-01-01

    One of the primary tasks of the Astrochemistry Laboratory at Ames Research Center is to use laboratory simulations to study the chemical processes that occur in dense interstellar clouds. Since new stars are formed in these clouds, their materials may be responsible for the delivery of organics to new habitable planets and may play important roles in the origin of life. These clouds are extremely cold (less than 50 kelvin), and most of the volatiles in these clouds are condensed onto dust grains as thin ice mantles. These ices are exposed to cosmic rays and ultraviolet (UV) photons that break chemical bonds and result in the production of complex molecules when the ices are warmed (as they would be when incorporated into a star-forming region). Using cryovacuum systems and UV lamps, this study simulates the conditions of these clouds and studies the resulting chemistry. Some of the areas of progress made in 1999 are described below. It shows some of the types of molecules that may be formed in the interstellar medium. Laboratory simulations have already confirmed that many of these compounds are made under these conditions.

  11. Application of vaccination protocols to manage beef cattle productivity and mitigate production risk 

    E-print Network

    Horne, Willy J.

    2010-01-16

    The U.S. beef industry is very large with many inter-connected facets. Nutrition and health are key components of a system striving to compete economically while striving to produce a high quality product. The decisions made in one part...

  12. Evaluation and redesign of manual material handling in a vaccine production centre's warehouse.

    PubMed

    Torres, Yaniel; Viña, Silvio

    2012-01-01

    This study was conducted in a warehouse at a vaccine production centre where improvement to existing storage and working conditions were sought through the construction of a new refrigerated store section (2-8C°). Warehousing tasks were videotaped and ergonomics analysis tools were used to assess the risk of developing MSDs. Specifically, these tools were the Rapid Entire Body Assessment (REBA) and the NIOSH equation. The current plant layout was sketched and analyzed to find possible targets for improvement trough the application of general work space design and ergonomics principles. Seven of the eight postures evaluated with REBA had a total score between 8 and 10, meaning a high risk, and only one was at a medium risk level. Nine of the eleven manual material handling tasks analyzed with the NIOSH equation had a Lifting Index between 1.14 and 1.80 and two had a recommended weight limit of 0 kg, indicating a need for job redesign. Solutions included the redesign of shelves, the design of a two-step stair and a trolley with adjustable height; also, changes in work methods were proposed by introducing a two-workers lifting strategy and job rotation, and, finally, a restructuring of plant layout was completed. PMID:22317092

  13. Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus (DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7) vaccines

    PubMed Central

    Kashiwagi, Yasuyo; Miyata, Akiko; Kumagai, Takuji; Maehara, Kouji; Suzuki, Eitarou; Nagai, Takao; Ozaki, Takao; Nishimura, Naoko; Okada, Kenji; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-01-01

    Haemophilus influenzae type b (Hib) and 7-valent pneumococcal (PCV7) vaccines both became recommended in Japan in 2010. In this study, cytokine production was investigated in peripheral blood mononuclear cells (PBMCs) cultures stimulated with diphtheria and tetanus toxoids combined with acellular pertussis vaccine (DPT), Hib, and PCV7 separately or concurrent different combinations, all as final off-the-shelf vaccines without the individual vaccine components as controls. Higher IL-1? levels were produced when cultures were stimulated with PCV than with DPT or Hib, and the concurrent stimulation including PCV7 enhanced the production of IL-1?. Although Hib induced higher levels of IL-6, no significant difference was observed in IL-6 production with the concurrent stimulation. The concurrent stimulation with Hib/PCV7 and DPT/Hib/PCV7 produced higher levels of TNF-? and human G-CSF. Cytokine profiles were examined in serum samples obtained from 61 vaccine recipients with febrile reactions and 18 recipients without febrile illness within 24 h of vaccination. No significant difference was observed in cytokine levels of IL-1?, IL-4, IL-6, IL-10, IL-12, IFN-?, MIP-1, TNF-?, and prostaglandin E2 (PGE2) in sera between the two groups. However, significantly higher levels of human G-CSF were observed in recipients with febrile illness than in those without febrile reactions. Further investigations of the significance of elevated serum G-CSF levels are required in vaccine recipients with febrile illness. PMID:24589970

  14. FDA: CVaccines, Blood & Biologics

    NSDL National Science Digital Library

    The mission of the Food and Drug Administration's (FDA) Vaccines, Blood & Biologics program is "to protect and enhance the public health through the regulation of biological and related products including blood, vaccines, allergenics, tissues, and cellular and gene therapies." Their mission is an important one, and consumers and scientists will want to bookmark this page and return to it on a regular basis. On the right-hand side of the page, visitors can sign up for their RSS feed, check out the "About" section, and read through their FAQ. In the center of the page, visitors can peruse the "Hot Topics", which at any given moment might include information on influenza vaccinations or product recalls or withdrawals. The site is rounded out by topical guide to the site along the left-hand side of the homepage.

  15. A melanoma helper peptide vaccine increases Th1 cytokine production by leukocytes in peripheral blood and immunized lymph nodes

    PubMed Central

    2014-01-01

    Background Cancers produce soluble and cell-associated molecules that can suppress or alter antitumor immunity. Preclinical studies suggest the disease burden may alter the cytokine profile of helper T cell responses to cancer antigens. We studied cytokine production by helper T cells responding to vaccination with 6 melanoma helper peptides (6MHP) in blood and lymph nodes. Methods Twenty-three patients with stage IIIB-IV melanoma received a 6MHP vaccine. Antigen-reactive T cells from blood and draining lymph nodes were cultured, exposed to antigen, and then supernatants (days 2 and 5) were assayed for Th1 and Th2 cytokines. Results from 4 time points were compared to pre-vaccine levels. Results Cytokine responses to vaccinating peptides were observed in 83% of patients. Th1 favoring responses were most common (17 of 19 responders). The most abundant cytokines produced were IFN-? and IL-5 in the PBMC’s. IL-2 responses predominated in cells obtained from draining lymph nodes in 2-day culture but not in 5-day cultures. Patients with clinically measurable disease produced similar levels of total cytokine and similar degree of Th1 polarization as patients with no evidence of disease (NED). Conclusions The MHC class II-associated peptides used in this study induced helper T cells with a Th1-biased cytokine response in both PBMC and sentinel immunized nodes. Most patients can mount a Th1 dominant response to these peptides. Future studies are needed to test newer vaccine adjuvants in combination with these peptides. Trial registration CDR0000378171, Clinicaltrials: NCT00089219. PMID:25126421

  16. Home Biology Medicine Technology Products News Definition Dictionary Movies Links Whole Site Goog

    E-print Network

    Chiao, Jung-Chih

    Home Biology Medicine Technology Products News Definition Dictionary Movies Links Search RSS Whole Definition Medicine Definition Biology Technology Medicine Technology Biology Dictionary Medicine Dictionary patterns that may play a part in the acid reflux. Researchers say patients shouldnt feel anything

  17. Towards universal influenza vaccines?

    PubMed Central

    Osterhaus, Ab; Fouchier, Ron; Rimmelzwaan, Guus

    2011-01-01

    Vaccination is the most cost-effective way to reduce the considerable disease burden of seasonal influenza. Although seasonal influenza vaccines are effective, their performance in the elderly and immunocompromised individuals would benefit from improvement. Major problems related to the development and production of pandemic influenza vaccines are response time and production capacity as well as vaccine efficacy and safety. Several improvements can be envisaged. Vaccine production technologies based on embryonated chicken eggs may be replaced by cell culture techniques. Reverse genetics techniques can speed up the generation of seed viruses and new mathematical modelling methods improve vaccine strain selection. Better understanding of the correlates of immune-mediated protection may lead to new vaccine targets besides the viral haemagglutinin, like the neuraminidase and M2 proteins. In addition, the role of cell-mediated immunity could be better exploited. New adjuvants have recently been shown to increase the breadth and the duration of influenza vaccine-induced protection. Other studies have shown that influenza vaccines based on different viral vector systems may also induce broad protection. It is to be expected that these developments may lead to more universal influenza vaccines that elicit broader and longer protection, and can be produced more efficiently. PMID:21893539

  18. Systems Biology of Recombinant Protein Production in Bacillus megaterium

    NASA Astrophysics Data System (ADS)

    Biedendieck, Rebekka; Bunk, Boyke; Fürch, Tobias; Franco-Lara, Ezequiel; Jahn, Martina; Jahn, Dieter

    Over the last two decades the Gram-positive bacterium Bacillus megaterium was systematically developed to a useful alternative protein production host. Multiple vector systems for high yield intra- and extracellular protein production were constructed. Strong inducible promoters were combined with DNA sequences for optimised ribosome binding sites, various leader peptides for protein export and N- as well as C-terminal affinity tags for affinity chromatographic purification of the desired protein. High cell density cultivation and recombinant protein production were successfully tested. For further system biology based control and optimisation of the production process the genomes of two B. megaterium strains were completely elucidated, DNA arrays designed, proteome, fluxome and metabolome analyses performed and all data integrated using the bioinformatics platform MEGABAC. Now, solid theoretical and experimental bases for primary modeling attempts of the production process are available.

  19. MIDGE Technology for the Production of a Fourfold Gene-Modified, Allogenic Cell-Based Vaccine for Cancer Therapy.

    PubMed

    Schmidt, Manuel; Volz, Barbara; Großmann, Patrick; Heinrich, Kerstin; Wittig, Burghardt

    2015-01-01

    Gene modification of eukaryotic cells by electroporation is a widely used method to express selected genes in a defined cell population for various purposes, like gene correction or production of therapeutics. Here, we describe the generation of a cell-based tumor vaccine via fourfold transient gene modification of a human renal cell carcinoma (RCC) cell line for high expression of CD80, CD154, GM-CSF, and IL-7 by use of MIDGE(®) vectors. The two co-stimulatory molecules CD80 and CD154 are expressed at the cell surface, whereas the two cytokines GM-CSF and IL-7 are secreted yielding cells with enhanced immunological properties. These fourfold gene-modified cells have been used as a cell-based tumor vaccine for the treatment of RCC. PMID:26072400

  20. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological...

  1. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological...

  2. An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies

    Microsoft Academic Search

    Itay Wiser; Ran D. Balicer; Dani Cohen

    2007-01-01

    The threat of using variola virus in a bioterrorist attack urged different countries to renew the production of traditional vaccines and develop new generations of smallpox vaccines. Manufacturers try to combine smallpox vaccine past experience with technological advances in vaccine development to achieve protection similar to that of the traditional vaccines with a higher level of safety and fewer contraindications.

  3. Formate Formation and Formate Conversion in Biological Fuels Production

    PubMed Central

    Crable, Bryan R.; Plugge, Caroline M.; McInerney, Michael J.; Stams, Alfons J. M.

    2011-01-01

    Biomethanation is a mature technology for fuel production. Fourth generation biofuels research will focus on sequestering CO2 and providing carbon-neutral or carbon-negative strategies to cope with dwindling fossil fuel supplies and environmental impact. Formate is an important intermediate in the methanogenic breakdown of complex organic material and serves as an important precursor for biological fuels production in the form of methane, hydrogen, and potentially methanol. Formate is produced by either CoA-dependent cleavage of pyruvate or enzymatic reduction of CO2 in an NADH- or ferredoxin-dependent manner. Formate is consumed through oxidation to CO2 and H2 or can be further reduced via the Wood-Ljungdahl pathway for carbon fixation or industrially for the production of methanol. Here, we review the enzymes involved in the interconversion of formate and discuss potential applications for biofuels production. PMID:21687599

  4. Overview of marker vaccine and differential diagnostic test technology

    Microsoft Academic Search

    Louise M. Henderson

    2005-01-01

    Recent advances in molecular biology, immunology, microbiology, genetics and microbial pathogenesis have lead to the development of a wide variety of new approaches for developing safer and more effective vaccines based on designs such as subunit vaccines, gene deleted vaccines, live vectored vaccines, and DNA mediated vaccines. Technology tools can be as basic as identifying naturally occurring strains with deletions

  5. Vaccination and anaphylaxis

    Microsoft Academic Search

    Hanne Nokleby

    2006-01-01

    The incidence of anaphylactic or severe allergic reactions to vaccines is very low, less than one case per million vaccine\\u000a doses. Larger studies from later years report no deaths. The cause of the reaction is usually not the immunizing antigen itself,\\u000a but rather some other vaccine ingredient such as egg protein from the production process or gelatin added as a

  6. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...Calculation of patent term extension for a veterinary biological product. 1.779 Section...Calculation of patent term extension for a veterinary biological product. (a) If a determination...pursuant to § 1.750 that a patent for a veterinary biological product is eligible...

  7. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...Calculation of patent term extension for a veterinary biological product. 1.779 Section...Calculation of patent term extension for a veterinary biological product. (a) If a determination...pursuant to § 1.750 that a patent for a veterinary biological product is eligible...

  8. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...Calculation of patent term extension for a veterinary biological product. 1.779 Section...Calculation of patent term extension for a veterinary biological product. (a) If a determination...pursuant to § 1.750 that a patent for a veterinary biological product is eligible...

  9. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...Calculation of patent term extension for a veterinary biological product. 1.779 Section...Calculation of patent term extension for a veterinary biological product. (a) If a determination...pursuant to § 1.750 that a patent for a veterinary biological product is eligible...

  10. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...Calculation of patent term extension for a veterinary biological product. 1.779 Section...Calculation of patent term extension for a veterinary biological product. (a) If a determination...pursuant to § 1.750 that a patent for a veterinary biological product is eligible...

  11. Beware of Products Promising Miracle Weight Loss

    MedlinePLUS Videos and Cool Tools

    ... Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to ... Search FDA Submit search Popular Content Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics ...

  12. Current approaches to vaccine preparation

    PubMed Central

    Liu, Jiang-Jian; Cepica, Arnost

    1990-01-01

    Numerous conventional vaccines for animal use are currently available, and many of these vaccines have been instrumental in the control of infectious diseases of major economic importance. A vaccine has even been instrumental in global eradication of smallpox, an important human disease. However, many of the current vaccines are deficient in efficiency, potency, or safety. It has been recognized that the conventional methodologies are a limitation to further vaccine development. Introduction of monoclonal antibodies, recombinant DNA, and protein engineering techniques has facilitated a rather rapid increase in the knowledge of pathogenetic mechanisms, as well as of protective antigens at the molecular level. This knowledge provides the basis for development of a new generation of vaccines. As a rule, these vaccines contain purified immunogens, or even isolated epitopes, identified and prepared by molecular biological techniques. The efforts to find better delivery systems and better adjuvants accompany the research on vaccines. PMID:17423533

  13. Adjuvants for allergy vaccines

    PubMed Central

    Moingeon, Philippe

    2012-01-01

    Allergen-specific immunotherapy is currently performed via either the subcutaneous or sublingual routes as a treatment for type I (IgE dependent) allergies. Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts in the absence of any immunopotentiator. Adjuvants to be included in the future in products for allergen specific immunotherapy should ideally enhance Th1 and CD4+ regulatory T cell responses. Imunomodulators impacting dendritic or T cell functions to induce IL10, IL12 and IFN? production are being investigated in preclinical allergy models. Such candidate adjuvants encompass synthetic or biological immunopotentiators such as glucocorticoids, 1,25-dihydroxy vitamin D3, selected probiotic strains (e.g., Lactobacillus and Bifidobacterium species) as well as TLR2 (Pam3CSK4), TLR4 (monophosphoryl lipid A, synthetic lipid A analogs) or TLR9 (CpGs) ligands. Furthermore, the use of vector systems such as mucoadhesive particules, virus-like particles or liposomes are being considered to enhance allergen uptake by tolerogenic antigen presenting cells present in mucosal tissues. PMID:23095872

  14. Is new always better than old?: The development of human vaccines for anthrax.

    PubMed

    Baillie, Leslie W

    2009-12-01

    Anthrax is caused by a Gram-positive aerobic spore-forming bacillus called Bacillus anthracis. Although primarily a disease of animals, it can also infect man, sometimes with fatal consequences. As a result of concerns over the illicit use of this organism, considerable effort is focused on the development of therapies capable of conferring protection against anthrax. while effective concerns over the toxicity of the current vaccines have driven the development of second-generation products. Recombinant Protective Antigen (rPA), the nontoxic cell-binding component of anthrax lethal toxin, is the principal immunogen of the vaccines currently undergoing human clinical trials. While these new vaccines are likely to show reduced side effects they will still require multiple needle based dosing and the inclusion of the adjuvant alum which will make them expensive to administer and stockpile. To address these issues, researchers are seeking to develop vaccine formulations capable of stimulating rapid protection following needle-free injection which are stable at room temperature to facilitate stockpiling and mass vaccination programs. Recent concerns over the potential use of molecular biology to engineer vaccine resistant strains has prompted investigators to identify additional vaccine targets with which to extend the spectrum of protection conferred by rPA. While the injection of research dollars has seen a dramatic expansion of the anthrax vaccine field it is sobering to remember that work to develop the current second generation vaccines began around the time of the first gulf war. Almost two decades and millions of dollars later we still do not have a replacement vaccine and even when we do some argue that the spectrum of protection that it confers will not be as broad as the vaccine it replaces. If we are to respond effectively to emerging biological threats we need to develop processes that generate protective vaccines in a meaningful time frame and yield products in months not decades! PMID:19786839

  15. Anthrax vaccination strategies

    PubMed Central

    Cybulski, Robert J.; Sanz, Patrick; O'Brien, Alison D.

    2009-01-01

    The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies. PMID:19729034

  16. Anthrax vaccination strategies.

    PubMed

    Cybulski, Robert J; Sanz, Patrick; O'Brien, Alison D

    2009-12-01

    The biological attack conducted through the US postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain US Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies. PMID:19729034

  17. Vaccination against infectious diseases: what is promising?

    PubMed

    Doerr, Hans Wilhelm; Berger, Annemarie

    2014-12-01

    Vaccination has proven to be one of the best weapons protecting the mankind against infectious diseases. Along with the huge progress in microbiology, numerous highly efficacious and safe vaccines have been produced by conventional technology (cultivation), by the use of molecular biology (genetic modification), or by synthetic chemistry. Sterilising prevention is achieved by the stimulation of antibody production, while the stimulation of cell-mediated immune responses may prevent the outbreak of disease in consequence of an acute or reactivated infection. From several examples, two rules are deduced to evaluate the perspectives of future vaccine developments: They are promising, if (1) the natural infectious disease induces immunity or (2) passive immunisation (transfer of antibodies, adoptive transfer of lymphocytes) is successful in preventing infection. PMID:25064610

  18. Production of Inactivated Influenza H5N1 Vaccines from MDCK Cells in Serum-Free Medium

    PubMed Central

    Hu, Alan Yung-Chih; Tseng, Yu-Fen; Weng, Tsai-Chuan; Liao, Chien-Chun; Wu, Johnson; Chou, Ai-Hsiang; Chao, Hsin-Ju; Gu, Anna; Chen, Janice; Lin, Su-Chen; Hsiao, Chia-Hsin; Wu, Suh-Chin; Chong, Pele

    2011-01-01

    Background Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK) cells grown in a serum-free (SF) medium microcarrier cell culture system. Principal Finding The current study has evaluated the performance of cell adaptation switched from serum-containing (SC) medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3×106 cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA) units/50 µL and 7.1±0.3×108 pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. Conclusions The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production. PMID:21283675

  19. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    NASA Astrophysics Data System (ADS)

    May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan

    2004-09-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  20. Typhoid Vaccine

    MedlinePLUS

    ... risks from typhoid vaccine?Like any medicine, a vaccine could cause a serious problem, such as a severe allergic reaction. The risk of typhoid vaccine causing serious harm, or death, is extremely small. ...

  1. Vaccine Shortages

    MedlinePLUS

    ... part of their regular immunizations) and others. What causes vaccine shortages? A vaccine shortage can occur for many ... quickly enough. Often, a combination of these factors causes a vaccine shortage in one or more areas of the ...

  2. Against vaccine assay secrecy.

    PubMed

    Herder, Matthew; Hatchette, Todd F; Halperin, Scott A; Langley, Joanne M

    2015-01-01

    Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canada's access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors. PMID:25826194

  3. Anti-cattle tick vaccines: Many candidate antigens, but will a commercially viable product emerge?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is an invited paper from the editor-in-chief of International Journal for Parasitology who requested a Current Opinion manuscript to discuss the status of anti-cattle tick vaccine research. Arguably the world's most significant arthropod pest of cattle, control of the cattle tick, Rhipicephalus...

  4. GMP production of pDERMATT for vaccination against melanoma in a phase I clinical trial.

    PubMed

    Quaak, S G L; van den Berg, J H; Toebes, M; Schumacher, T N M; Haanen, J B A G; Beijnen, J H; Nuijen, B

    2008-10-01

    For the treatment of melanoma DNA vaccines are a promising therapeutic approach. In our institute a plasmid encoding a melanoma-associated epitope (MART-1) and an immunostimulatory sequence (tetanus toxin fragment-c) termed pDERMATT was developed. In a phase I study the plasmid will be administered intradermally using a newly developed tattoo strategy to assess the toxicity and efficacy of inducing tumor-specific T-cell immunity. To facilitate this study a Good Manufacturing Practice (GMP)-compliant plasmid manufacturing process was set up and a pharmaceutical dosage form was developed. Each batch resulted in approximately 200mg plasmid DNA of a high purity >90% supercoiled DNA, an A260/280 ratio 1.80-1.95, undetectable or extremely low residual endotoxins, Escherichia coli host cell protein, RNA, and DNA. In the manufacturing process no animal derived enzymes like RNase or potentially harmful organic solvents are used. After sterile filtration the concentration of the plasmid solution is approximately 1.1mg/mL. For the scheduled phase I study a concentration of 5mg/mL is desired, and further concentration of the solution is achieved by lyophilisation. The formulation solution is composed of 1mg/mL pDERMATT and 20mg/mL sucrose in Water for Injections. Upon reconstitution with a five times smaller volume an isotonic sucrose solution containing 5mg/mL pDERMATT is obtained. Lyophilised pDERMATT is sterile with >90% supercoiled DNA, an A260-280 ratio 1.80-1.95, content 90-110% of labeled, and residual water content <2% (w/w). The product yields the predicted profile upon restriction-enzyme digestion, is highly immunogenic as confirmed in an in vivo mouse model, and stable for at least six months at 5 degrees C. We have not only developed a reproducible process to manufacture pharmaceutical grade plasmid DNA but also a stable dosage form for the use in clinical trials. PMID:18606527

  5. Vaccine acceptance

    PubMed Central

    Ford, John A; Mahgoub, Hamid; Shankar, Ananda Giri

    2013-01-01

    The United Kingdom has had a long history with vaccine acceptability dating back to Edward Jenner’s theory of small pox vaccination. More recently, the discredited, Wakefield study published in 1998 continues to cause MMR skepticism. In pregnant women pertussis vaccination has been considerably more successful than influenza vaccination. Influenza vaccine uptake in healthcare workers remains poor. The media, politicians, and health reforms have contributed to the mixed coverage for these vaccines. In this article we examine vaccine acceptability from a UK perspective, and consider the future impact this is likely to have on the introduction of rotavirus and shingles vaccine in the UK in 2013. PMID:24025731

  6. Production of biologically active recombinant human lactoferrin in Aspergillus oryzae.

    PubMed

    Ward, P P; Lo, J Y; Duke, M; May, G S; Headon, D R; Conneely, O M

    1992-07-01

    We report the production of recombinant human lactoferrin in Aspergillus oryzae. Expression of human lactoferrin (hLF), a 78 kD glycoprotein, was achieved by placing the cDNA under the control of the A. oryzae alpha-amylase promoter and the 3' flanking region of the A. niger glucoamylase gene. Using this system, hLF is expressed and secreted into the growth medium at levels up to 25 mg/l. The recombinant lactoferrin is indistinguishable from human milk lactoferrin with respect to its size, immunoreactivity, and iron-binding capacity. The recombinant protein appears to be appropriately N-linked glycosylated and correctly processed at the N-terminus by the A. oryzae secretory apparatus. Lactoferrin is the largest heterologous protein and the first mammalian glycoprotein expressed in the Aspergillus system to date. Hence, this expression system appears suitable for the large-scale production and secretion of biologically active mammalian glycoproteins. PMID:1368268

  7. Systems biological approaches towards understanding cellulase production by Trichoderma reesei

    PubMed Central

    Kubicek, Christian P.

    2013-01-01

    Recent progress and improvement in “-omics” technologies has made it possible to study the physiology of organisms by integrated and genome-wide approaches. This bears the advantage that the global response, rather than isolated pathways and circuits within an organism, can be investigated (“systems biology”). The sequencing of the genome of Trichoderma reesei (teleomorph Hypocrea jecorina), a fungus that serves as a major producer of biomass-degrading enzymes for the use of renewable lignocellulosic material towards production of biofuels and biorefineries, has offered the possibility to study this organism and its enzyme production on a genome wide scale. In this review, I will highlight the use of genomics, transcriptomics, proteomics and metabolomics towards an improved and novel understanding of the biochemical processes that involve in the massive overproduction of secreted proteins. PMID:22750088

  8. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...and sale of a serial or subserial of a veterinary biological product under the provisions...paragraph (a) or (b) of this section, veterinary biologics licensees or permittees shall...serial(s) or subserial(s) of any veterinary biological product pending further...

  9. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...and sale of a serial or subserial of a veterinary biological product under the provisions...paragraph (a) or (b) of this section, veterinary biologics licensees or permittees shall...serial(s) or subserial(s) of any veterinary biological product pending further...

  10. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...and sale of a serial or subserial of a veterinary biological product under the provisions...paragraph (a) or (b) of this section, veterinary biologics licensees or permittees shall...serial(s) or subserial(s) of any veterinary biological product pending further...

  11. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...and sale of a serial or subserial of a veterinary biological product under the provisions...paragraph (a) or (b) of this section, veterinary biologics licensees or permittees shall...serial(s) or subserial(s) of any veterinary biological product pending further...

  12. Anthrax vaccines.

    PubMed

    Splino, Miroslav; Patocka, Jiri; Prymula, Roman; Chlibek, Roman

    2005-01-01

    Anthrax, an uncommon disease in humans, is caused by a large bacterium, Bacillus anthracis. The risk of inhalation infection is the main indication for anthrax vaccination. Pre-exposure vaccination is provided by an acellular vaccine (anthrax vaccine adsorbed or AVA), which contains anthrax toxin elements and results in protective immunity after 3 to 6 doses. Anthrax vaccine precipitated (AVP) is administered at primovaccination in 3 doses with a booster dose after 6 months. To evoke and maintain protective immunity, it is necessary to administer a booster dose once at 12 months. In Russia, live spore vaccine (STI) has been used in a two-dose schedule. Current anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever). Serious adverse reactions occur in about 1% of vaccinations. New second-generation vaccines in current research programs include recombinant live vaccines and recombinant sub-unit vaccines. PMID:15977694

  13. Plant-based rapid production of recombinant subunit hemagglutinin vaccines targeting H1N1 and H5N1 influenza.

    PubMed

    Shoji, Yoko; Chichester, Jessica A; Jones, Mark; Manceva, Slobodanka D; Damon, Emily; Mett, Vadim; Musiychuk, Konstantin; Bi, Hong; Farrance, Christine; Shamloul, Moneim; Kushnir, Natasha; Sharma, Satish; Yusibov, Vidadi

    2011-01-01

    In 2009, a novel H1N1 swine influenza virus was isolated from infected humans in Mexico and the United States, and rapidly spread around the world. Another virus, a highly pathogenic avian influenza virus of the H5N1 subtype, identified by the World Health Organization as a potential pandemic threat in 1997, continues to be a significant risk. While vaccination is the preferred strategy for the prevention and control of influenza infections, the traditional egg-based approach to producing influenza vaccines does not provide sufficient capacity and adequate speed to satisfy global needs to combat newly emerging strains, seasonal or potentially pandemic. Significant efforts are underway to develop and implement new cell substrates with improved efficiency for influenza vaccine development and manufacturing. In recent years, plants have been used to produce recombinant proteins including subunit vaccines and antibodies. The main advantages of using plant systems for the production of vaccine antigens against influenza are their independence from pathogenic viruses, and cost and time efficiency. Here, we describe the large-scale production of recombinant hemagglutinin proteins from A/California/04/09 (H1N1) and A/Indonesia/05/05 (H5N1) strains of influenza virus in Nicotiana benthamiana plants, and their immunogenicity (serum hemagglutination inhibition and virus neutralizing antibodies), and safety in animal models. These results support the testing of these candidate vaccines in human volunteers and also the utility of our plant expression system for large-scale recombinant influenza vaccine production. PMID:21266846

  14. Biological production of monoethanolamine by engineered Pseudomonas putida S12.

    PubMed

    Foti, Mirjam; Médici, Rosario; Ruijssenaars, Harald J

    2013-09-10

    Pseudomonas putida S12 was engineered for the production of monoethanolamine (MEA) from glucose via the decarboxylation of the central metabolite L-serine, which is catalyzed by the enzyme L-serine decarboxylase (SDC). The host was first evaluated for its tolerance towards MEA as well as its endogenous ability to degrade this alkanolamine. Growth inhibition was observed at MEA concentrations above 100 mM, but growth was never completely arrested even at 750 mM of MEA. P. putida S12 was able to catabolize MEA in the absence of ammonia, but deletion of the eutBC genes that encode ethanolamine ammonia-lyase (EAL) enzyme sufficed to eliminate this capacity. For the biological production of MEA, the sdc genes from Arabidopsis thaliana (full-length and a truncated version) and Volvox carteri were expressed in P. putida S12. From 20 mM of glucose, negligible amounts of MEA were produced by P. putida S12 ?eutBC expressing the sdc genes from A. thaliana and V. carteri. However, 0.07 mmol of MEA was obtained per g of cell dry weight of P. putida S12 ?eutBC expressing the truncated variant of the A. thaliana SDC. When the medium was supplemented with L-serine (30 mM), MEA production increased to 1.25 mmol MEA g?¹ CDW, demonstrating that L-serine availability was limiting MEA production. PMID:23876477

  15. CpG used as an adjuvant for an adenovirus-based Venezuelan equine encephalitis virus vaccine increases the immune response to the vector, but not to the transgene product.

    PubMed

    Perkins, Stuart D; Williams, Amanda J; O'Brien, Lyn M; Laws, Thomas R; Phillpotts, Robert J

    2008-12-01

    An adenovirus-based (ad-based) vaccine delivering antigens from the Alphavirus Venezuelan equine encephalitis virus (VEEV) is a strategy that offers clinical potential. A vaccine against VEEV is desirable because of the re-emerging nature of this virus, and also the potential that it may be used as a biological weapon. This study was designed to investigate whether the co-administration of CpG oligodeoxynucleotides (ODNs) with an ad-based VEEV vaccine could enhance the protective efficacy of the vaccine. We report that the co-administration of CpG ODN was unable to increase VEEV-specific antibody responses in mice, and was unable to increase the protective efficacy of the vaccine against aerosol challenge with virulent VEEV. However, it was noted that antibody responses directed against the adenovirus vaccine vector were increased, which may be detrimental, particularly in the context of homologous boosting. PMID:19115934

  16. Production and characterization of vaccines based on flaviviruses defective in replication

    SciTech Connect

    Mason, Peter W. [Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019 (United States); Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019 (United States); Sealy Center for Vaccine Development, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019 (United States); Shustov, Alexandr V. [Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019 (United States); Frolov, Ilya [Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019 (United States)]. E-mail: ivfrolov@utmb.edu

    2006-08-01

    To develop new vaccine candidates for flavivirus infections, we have engineered two flaviviruses, yellow fever virus (YFV) and West Nile virus (WNV), that are deficient in replication. These defective pseudoinfectious viruses (PIVs) lack a functional copy of the capsid (C) gene in their genomes and are incapable of causing spreading infection upon infection of cells both in vivo and in vitro. However, they produce extracellular E protein in form of secreted subviral particles (SVPs) that are known to be an effective immunogen. PIVs can be efficiently propagated in trans-complementing cell lines making high levels of C or all three viral structural proteins. PIVs derived from YFV and WNV, demonstrated very high safety and immunization produced high levels of neutralizing antibodies and protective immune response. Such defective flaviviruses can be produced in large scale under low biocontainment conditions and should be useful for diagnostic or vaccine applications.

  17. A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS.

    PubMed

    Keilholz, Ulrich; Letsch, Anne; Busse, Antonia; Asemissen, Anne Marie; Bauer, Sandra; Blau, Igor Wolfgang; Hofmann, Wolf-Karsten; Uharek, Lutz; Thiel, Eckhard; Scheibenbogen, Carmen

    2009-06-25

    This study investigated the immunogenicity of Wilms tumor gene product 1 (WT1)-peptide vaccination in WT1-expressing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients without curative treatment option. Vaccination consisted of granulocyte-macrophage colony-stimulating factor subcutaneously days 1 to 4, and WT1.126-134 peptide and 1 mg keyhole limpet hemocyanin on day 3. The initial 9 patients received 4 vaccinations biweekly, then monthly, and the subsequent 10 patients received continual biweekly vaccination. Seventeen AML patients and 2 refractory anemia with excess blasts patients received a median of 11 vaccinations. Treatment was well tolerated. Objective responses in AML patients were 10 stable diseases (SDs) including 4 SDs with more than 50% blast reduction and 2 with hematologic improvement. An additional 4 patients had clinical benefit after initial progression, including 1 complete remission and 3 SDs. WT1 mRNA levels decreased at least 3-fold from baseline in 35% of patients. In 8 of 18 patients, WT1-tetramer(+) T cells increased in blood and in 8 of 17 patients in bone marrow, with a median frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, warranting further investigations. PMID:19389880

  18. GMP production of pDERMATT for vaccination against melanoma in a phase I clinical trial

    Microsoft Academic Search

    S. G. L. Quaak; J. H. van den Berg; M. Toebes; T. N. M. Schumacher; J. B. A. G. Haanen; J. H. Beijnen; B. Nuijen

    2008-01-01

    For the treatment of melanoma DNA vaccines are a promising therapeutic approach. In our institute a plasmid encoding a melanoma-associated epitope (MART-1) and an immunostimulatory sequence (tetanus toxin fragment-c) termed pDERMATT was developed. In a phase I study the plasmid will be administered intradermally using a newly developed tattoo strategy to assess the toxicity and efficacy of inducing tumor-specific T-cell

  19. Suitability of Gray Water for Hydroponic Crop Production Following Biological and Physical Chemical and Biological Subsystems

    NASA Technical Reports Server (NTRS)

    Bubenheim, David L.; Harper, Lynn D.; Wignarajah, Kanapathipillai; Greene, Catherine

    1994-01-01

    The water present in waste streams from a human habitat must be recycled in Controlled Ecological Life Support Systems (CELSS) to limit resupply needs and attain self-sufficiency. Plants play an important role in providing food, regenerating air, and producing purified water via transpiration. However, we have shown that the surfactants present in hygiene waste water have acute toxic effects on plant growth (Bubenheim et al. 1994; Greene et al., 1994). These phytotoxic affects can be mitigated by allowing the microbial population on the root surface to degrade the surfactant, however, a significant suppression (several days) in crop performance is experienced prior to reaching sub-toxic surfactant levels and plant recovery. An effective alternative is to stabilize the microbial population responsible for degradation of the surfactant on an aerobic bioreactor and process the waste water prior to utilization in the hydroponic solution (Wisniewski and Bubenheim, 1993). A sensitive bioassay indicates that the surfactant phytotoxicity is suppressed by more than 90% within 5 hours of introduction of the gray water to the bioreactor; processing for more than 12 hours degrades more than 99% of the phytotoxin. Vapor Compression Distillation (VCD) is a physical / chemical method for water purification which employees sequential distillation steps to separate water from solids and to volatilize contaminants. The solids from the waste water are concentrated in a brine and the pure product water (70 - 90% of the total waste water volume depending on operating conditions) retains non of the phytotoxic effects. Results of the bioassay were used to guide evaluations of the suitability of recovered gray water following biological and VCD processing for hydroponic lettuce production in controlled environments. Lettuce crops were grown for 28 days with 100% of the input water supplied with recovered water from the biological processor or VCD. When compared with the growth of plants in control hydroponic solution containing pure deionized water, no growth difference could be measured resulting from any of the recovered water treatments. Both biological treatment and VCD offer alternative technology approaches to recovering water from waste streams appropriate for input into a crop production system. A high level of crop performance (food, air, and water production) can be maintained with either processor; selection decisions can be based on other factors regarding system integration.

  20. Pricing of new vaccines

    PubMed Central

    McGlone, Sarah M

    2010-01-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; (4) Quantify the incremental value of the new vaccine's characteristics; (5) Determine vaccine positioning in the marketplace; (6) Estimate the vaccine price-demand curve; (7) Calculate vaccine costs (including those of manufacturing, distribution, and research and development); (8) Account for various legal, regulatory, third party payer and competitor factors; (9) Consider the overall product portfolio; (10) Set pricing objectives; (11) Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area. PMID:20861678

  1. Biological production of ethanol from coal. Final report

    SciTech Connect

    Not Available

    1992-12-01

    Due to the abundant supply of coal in the United States, significant research efforts have occurred over the past 15 years concerning the conversion of coal to liquid fuels. Researchers at the University of Arkansas have concentrated on a biological approach to coal liquefaction, starting with coal-derived synthesis gas as the raw material. Synthesis gas, a mixture of CO, H{sub 2}, CO{sub 2}, CH{sub 4} and sulfur gases, is first produced using traditional gasification techniques. The CO, CO{sub 2} and H{sub 2} are then converted to ethanol using a bacterial culture of Clostridium 1jungdahlii. Ethanol is the desired product if the resultant product stream is to be used as a liquid fuel. However, under normal operating conditions, the ``wild strain`` produces acetate in favor of ethanol in conjunction with growth in a 20:1 molar ratio. Research was performed to determine the conditions necessary to maximize not only the ratio of ethanol to acetate, but also to maximize the concentration of ethanol resulting in the product stream.

  2. Biochemical and biological characteristics of cross-reacting material 197 (CRM 197), a non-toxic mutant of diphtheria toxin: Use as a conjugation protein in vaccines and other potential clinical applications

    Microsoft Academic Search

    Michael Bröker; Paolo Costantino; Lisa DeTora; E. David McIntosh; Rino Rappuoli

    2011-01-01

    The biochemical and biological characteristics of CRM197 are reviewed. Polysaccharide protein conjugate vaccines represent an important technological advancement that allowed for protection against dangerous diseases in vulnerable populations such as infants. The first carrier proteins, diphtheria and tetanus toxoids, were chosen in the context of an extensive body of information describing their immunogenicity and safety profiles in clinical use. These

  3. PRODUCTION OF HOMOLOGOUS LIVE ATTENUATED CELL CULTURE VACCINE FOR THE CONTROL OF PESTE DES PETITS RUMINANTS IN SMALL RUMINANTS

    Microsoft Academic Search

    M. ASIM; A. RASHID; A. H. CHAUDHARY; M. S. NOOR

    Antibody response of a live-attenuated Peste des Petits Ruminants (PPR) cell culture vaccine was studied at Veterinary Research Institute, Lahore, Pakistan. For this purpose, one group of five sheep and 5 goats each was vaccinated subcutaneously with 1 ml reconstituted PPR vaccine and second group of five sheep and 5 goats was inoculated with 1 ml saline solution. Blood samples

  4. Antiradiation vaccine: Technology and development of prophylaxis, prevention and treatment of biological consequences from Heavy Ion irradiation.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Vecheslav

    Introduction: An anti-radiation vaccine could be an important part of a countermeasures reg-imen for effective radioprotection, immunoprophylaxis and immunotherapy of the acute radi-ation syndromes (ARS) after gamma-irradiation, neutron irradiation or heavy ion irradiation. Reliable protection of non-neoplastic regions of patients with different forms of cancer which undergo to heavy ion therapy ( e.g. Hadron-therapy) can significantly extend the efficiency of the therapeutic course. The protection of cosmonauts astronauts from the heavy ion ra-diation component of space radiation with specific immunoprophylaxis by the anti-radiation vaccine may be an important part of medical management for long term space missions. Meth-ods and experiments: 1. The Antiradiation Vaccine preparation -standard (mixture of toxoid form of Radiation Toxins -SRD-group) which include Cerebrovascular RT Neurotoxin, Car-diovascular RT Neurotoxin, Gastrointestinal RT Neurotoxin, Hematopoietic RT Hematotoxin. Radiation Toxins Specific Radiation Determinant Group were isolated from a central lymph of gamma-irradiated animals with Cerebrovascular, Cardiovascular, Gastrointestiinal, Hematopoi-etic forms of ARS. Devices for ?-radiation are "Panorama", "Puma". 2. Heavy ion exposure was accomplished at Department of Scientific Research Institute of Nuclear Physics, Dubna, Russia. The heavy ions irradiation was generated in heavy ion (Fe56) accelerator -UTI. Heavy Ion linear transfer energy -2000-2600 KeV mkm, 600 MeV U. Absorbed Dose -3820 Rad. 3. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A -control -10 rabbits; Group B -placebo -5 rabbits; Group C -radioprotectant Cystamine (50 mg kg)-5 rabbits, 15 minutes before irradiation -5 rabbits; Group D -radioprotectant Gammafos (Amifostine -400mg kg ), -5 rabbits; Group E -Antiradiation Vaccine: subcuta-neus administration or IM -2 ml of active substance, 14 days before irradiation -5 rabbits. 4. Results: Group A -100% mortality within two hours after heavy ion irradiation with clinical symptoms of the acute cerebrovascular and cardiovascular syndromes. Group B -100% mortal-ity within 15 hours following irradiation. Group C -100% mortality within 14-15 hours after irradiation. Group D -100% mortality within 15-16 hours after irradiation. In groups A-D, development of the acute radiation cerebrovascular and cardiovascular syndromes as well as ex-tensive burns of skin caused rapid death. Group E -100% mortality in 280-290 hours (12 days) following heavy ion irradiation while animals were exhibiting a combination or individual forms of the acute cerebrovascular, cardiovascular, and gastrointestinal forms and focal skin burns. Discussion: The Antiradiation Vaccine (ARV) and specific immune-prophylaxis are an effective method of neutralization of Radiation Toxins. Vaccination with the ARV significantly extended the survival time after irradiation with heavy ions from two hours up to 300 hours. Clinical signs, clinical features, symptoms were somewhat attenuated. Degree of clinical forms of the Acute Radiation Syndromes were diminished in their severity. Groups A-D demonstrated an extremely severe degree (Degree 4) of Cerebrovascular and Cardiovascular forms of the Acute Radiation Syndromes and lethality 100% was registered in a short time after irradiation. Radi-ation induced burns in this groups (with Cutaneous sub-syndrome of ARS -Degree 4) that were deep with extensive and total dysfunction and possible muscle involvement developed. Animals from group E -Radioprotectant -anti-radiation vaccine had demonstrated later development of the severe Degree 3 or even Degree 2-3 forms of Cerebrovascular and Cardiovascular forms of the ARS and a survival time of irradiated animals was significantly prolonged. Cutaneous sub-syndrome developed in Degree 3 or Degree 2-3. Our results have demonstrated the potential radioprotection efficacy of specific immune-prophylaxis with the Antiradiation vaccine against heavy ion irradiation.

  5. An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies.

    PubMed

    Wiser, Itay; Balicer, Ran D; Cohen, Dani

    2007-01-22

    The threat of using variola virus in a bioterrorist attack urged different countries to renew the production of traditional vaccines and develop new generations of smallpox vaccines. Manufacturers try to combine smallpox vaccine past experience with technological advances in vaccine development to achieve protection similar to that of the traditional vaccines with a higher level of safety and fewer contraindications. In light of the reported immunogenicity and reactogenicity of the stockpiled smallpox vaccines employed in the last immunization campaigns of "first responders", we review recently accumulated data on the assessment of new smallpox vaccine candidates and discuss their role in possible vaccination policies. PMID:17074424

  6. VACCINE INFORMATION STATEMENT Influenza Vaccine

    E-print Network

    Oklahoma, University of

    VACCINE INFORMATION STATEMENT Influenza Vaccine What You Need to Know (Flu Vaccine, Live idiomas. Visite www.immunize.org/vis 1 Why get vaccinated? Influenza ("flu") is a contagious disease by the influenza virus, and can be spread by coughing, sneezing, and close contact. Anyone can get flu

  7. VACCINE INFORMATION STATEMENT Influenza Vaccine

    E-print Network

    Oklahoma, University of

    VACCINE INFORMATION STATEMENT Influenza Vaccine What You Need to Know (Flu Vaccine, Inactivated.immunize.org/vis 1 Why get vaccinated? Influenza ("flu") is a contagious disease that spreads around the United States every winter, usually between October and May. Flu is caused by the influenza virus, and can

  8. VACCINE INFORMATION STATEMENT Influenza Vaccine

    E-print Network

    Lien, Jyh-Ming

    VACCINE INFORMATION STATEMENT Influenza Vaccine What You Need to Know (Flu Vaccine, Inactivated idiomas. Visite www.immunize.org/vis 1 Why get vaccinated? Influenza ("flu") is a contagious disease that spreads around the United States every winter, usually between October and May. Flu is caused by influenza

  9. Regulatory issues surrounding the temporary authorisation of animal vaccination in emergency situations: the example of bluetongue in Europe.

    PubMed

    Saegerman, C; Hubaux, M; Urbain, B; Lengelé, L; Berkvens, D

    2007-08-01

    A marketing authorisation for a veterinary vaccine is granted after the quality, safety and efficacy of the product have been assessed in accordance with legal standards. The assessment includes complete characterisation and identification of seed material and ingredients, laboratory and host animal safety and efficacy studies, stability studies, and post-licensing monitoring of field performance. This assessment may not be possible during the emergence of a new animal disease, but several mechanisms exist to allow for the availability of products in an emergency animal health situation, e.g. autogenous biologics, conditional licences, experimental and emergency use authorisations, the importation of products in use elsewhere in the world and pre-approved vaccine banks. Using the emergence of bluetongue in northern Europe as an example, the regulatory issues regarding the temporary authorisation of animal vaccination are described. Several conditions must be fulfilled before a temporary authorisation can be granted, e.g. inactivated vaccines should be used in order to exclude reversion to virulence and reassortment between vaccine viruses and/or field strains of the bluetongue virus; decision-making must be supported by scientific evidence and risk analysis; there must be a complete census of the susceptible animals that were vaccinated; vaccination protocols must be adhered to and there must be a scheme allowing for registration, delivery and follow-up of vaccination, and monitoring, analysis and, possibly, adjustment of field use of the vaccination. This temporary authorisation must be replaced by a full authorisation as quickly as possible. PMID:17892160

  10. 9 CFR 113.65 - Brucella Abortus Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.65 Brucella Abortus Vaccine. Brucella Abortus Vaccine...

  11. Current perspectives on conventional and novel vaccines against peste des petits ruminants.

    PubMed

    Liu, Fuxiao; Wu, Xiaodong; Liu, Wenhua; Li, Lin; Wang, Zhiliang

    2014-12-01

    Peste des petits ruminants (PPR) is an acute or subacute, highly contagious viral disease of small ruminants, characterized by fever, oculonasal discharges, stomatitis, diarrhoea and pneumonia. This disease is included in the OIE (Office International des Epizooties) list of notifiable terrestrial animal diseases. PPR was first described in the early 1940s in Côte d'Ivoire, and at present, PPR is mainly circulating in Western and Central Africa, the Arabian Peninsula and Southern Asia. Peste des petits ruminants virus (PPRV), the etiological agent of PPR, is classified into the genus Morbillivirus in the family Paramyxoviridae, as its biological and physicochemical features are closely related to the other morbilliviruses. The first homologous PPR vaccine was developed by an artificially attenuated PPRV, named as Nigeria 75/1, which has been widely used in the production of live attenuated vaccines to protect small ruminants. A new generation of PPR vaccine candidates can be genetically modified to differentiate infected from vaccinated animals (DIVA), which nevertheless is difficult to achieve by conventional vaccines. In this review, we systematically discussed a broad range of vaccines against PPR, including commercially available vaccines and potential vaccine candidates, and further DIVA strategies for immunization with the new generation vaccines. PMID:25224755

  12. Malaria vaccines in development.

    PubMed

    Ballou, W Ripley

    2005-08-01

    The recent infusion of public and private funding for malaria vaccine development has greatly accelerated the pace at which candidate malaria vaccines are entering the clinic. Recent promising results from vaccine trials carried out in malaria-naive and -endemic populations have revealed important insights into what will be required of a successful vaccine. Significant challenges lie ahead, not the least of which is insuring access of a malaria vaccine to the populations that need it most. Creative strategies, strong partnerships with developing countries, industry-like approaches to product development, and political vision and leadership on the part of wealthy nations will be critical to the successful implementation of this important new tool to reduce the intolerable burden of malaria. PMID:16083325

  13. Developing new smallpox vaccines.

    PubMed Central

    Rosenthal, S. R.; Merchlinsky, M.; Kleppinger, C.; Goldenthal, K. L.

    2001-01-01

    New stockpiles of smallpox vaccine are required as a contingency for protecting civilian and military personnel against deliberate dissemination of smallpox virus by terrorists or unfriendly governments. The smallpox vaccine in the current stockpile consists of a live animal poxvirus (Vaccinia virus [VACV]) that was grown on the skin of calves. Because of potential issues with controlling this earlier manufacturing process, which included scraping VACV lesions from calfskin, new vaccines are being developed and manufactured by using viral propagation on well-characterized cell substrates. We describe, from a regulatory perspective, the various strains of VACV, the adverse events associated with calf lymph-propagated smallpox vaccine, the issues regarding selection and use of cell substrates for vaccine production, and the issues involved in demonstrating evidence of safety and efficacy. PMID:11747717

  14. Cell surface display of highly pathogenic avian influenza hemagglutinin on the surface of Pichia pastoris cells using alpha-agglutinin for production of oral vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Yeast are an ideal organism to express viral antigens because yeast glycosylate proteins are more similar to mammals than bacteria, and expression of proteins in yeast is relatively fast and inexpensive. In addition to the convenience of production, for purposes of vaccination, yeast have been show...

  15. Vaccines, viruses, and voodoo.

    PubMed

    Borchers, Andrea T; Keen, Carl L; Shoenfeld, Yehuda; Silva, Joseph; Gershwin, M Eric

    2002-01-01

    Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease. PMID:12530114

  16. Attenuated and Replication-Competent Vaccinia Virus Strains M65 and M101 with Distinct Biology and Immunogenicity as Potential Vaccine Candidates against Pathogens

    PubMed Central

    Sánchez-Sampedro, Lucas; Gómez, Carmen Elena; Mejías-Pérez, Ernesto; Pérez-Jiménez, Eva; Oliveros, Juan Carlos

    2013-01-01

    Replication-competent poxvirus vectors with an attenuation phenotype and with a high immunogenic capacity of the foreign expressed antigen are being pursued as novel vaccine vectors against different pathogens. In this investigation, we have examined the replication and immunogenic characteristics of two vaccinia virus (VACV) mutants, M65 and M101. These mutants were generated after 65 and 101 serial passages of persistently infected Friend erythroleukemia (FEL) cells. In cultured cells of different origins, the mutants are replication competent and have growth kinetics similar to or slightly reduced in comparison with those of the parental Western Reserve (WR) virus strain. In normal and immune-suppressed infected mice, the mutants showed different levels of attenuation and pathogenicity in comparison with WR and modified vaccinia Ankara (MVA) strains. Wide genome analysis after deep sequencing revealed selected genomic deletions and mutations in a number of viral open reading frames (ORFs). Mice immunized in a DNA prime/mutant boost regimen with viral vectors expressing the LACK (Leishmania homologue for receptors of activated C kinase) antigen of Leishmania infantum showed protection or a delay in the onset of cutaneous leishmaniasis. Protection was similar to that triggered by MVA-LACK. In immunized mice, both polyfunctional CD4+ and CD8+ T cells with an effector memory phenotype were activated by the two mutants, but the DNA-LACK/M65-LACK protocol preferentially induced CD4+ whereas DNA-LACK/M101-LACK preferentially induced CD8+ T cell responses. Altogether, our findings showed the adaptive changes of the WR genome during long-term virus-host cell interaction and how the replication competency of M65 and M101 mutants confers distinct biological properties and immunogenicity in mice compared to those of the MVA strain. These mutants could have applicability for understanding VACV biology and as potential vaccine vectors against pathogens and tumors. PMID:23596295

  17. Biological removal of cationic fission products from nuclear wastewater.

    PubMed

    Ngwenya, N; Chirwa, E M N

    2011-01-01

    Nuclear energy is becoming a preferred energy source amidst rising concerns over the impacts of fossil fuel based energy on global warming and climate change. However, the radioactive waste generated during nuclear power generation contains harmful long-lived fission products such as strontium (Sr). In this study, cationic strontium uptake from solution by microbial cultures obtained from mine wastewater is evaluated. A high strontium removal capacity (q(max)) with maximum loading of 444 mg/g biomass was achieved by a mixed sulphate reducing bacteria (SRB) culture. Sr removal in SRB was facilitated by cell surface based electrostatic interactions with the formation of weak ionic bonds, as 68% of the adsorbed Sr(2+) was easily desorbed from the biomass in an ion exchange reaction with MgCl?. To a lesser extent, precipitation reactions were also found to account for the removal of Sr from aqueous solution as about 3% of the sorbed Sr was precipitated due to the presence of chemical ligands while the remainder occurred as an immobile fraction. Further analysis of the Sr-loaded SRB biomass by scanning electron microscopy (SEM) coupled to energy dispersive X-ray (EDX) confirmed extracellular Sr(2+) precipitation as a result of chemical interaction. In summary, the obtained results demonstrate the prospects of using biological technologies for the remediation of industrial wastewaters contaminated by fission products. PMID:21245563

  18. Competency development in antibody production in cancer cell biology

    SciTech Connect

    Park, M.S.

    1998-12-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The main objective of this project was to develop a rapid recombinant antibody production technology. To achieve the objective, the authors employed (1) production of recombinant antigens that are important for cell cycle regulation and DNA repair, (2) immunization and specific selection of antibody-producing lymphocytes using the flow cytometry and magnetic bead capturing procedure, (3) construction of single chain antibody library, (4) development of recombinant vectors that target, express, and regulate the expression of intracellular antibodies, and (5) specific inhibition of tumor cell growth in tissue culture. The authors have accomplished (1) optimization of a selection procedure to isolate antigen-specific lymphocytes, (2) optimization of the construction of a single-chain antibody library, and (3) development of a new antibody expression vector for intracellular immunization. The future direction of this research is to continue to test the potential use of the intracellular immunization procedure as a tool to study functions of biological molecules and as an immuno-cancer therapy procedure to inhibit the growth of cancer cells.

  19. Escherichia coli heat-labile toxin subunit B fusions with Streptococcus sobrinus antigens expressed by Salmonella typhimurium oral vaccine strains: importance of the linker for antigenicity and biological activities of the hybrid proteins.

    PubMed Central

    Jagusztyn-Krynicka, E K; Clark-Curtiss, J E; Curtiss, R

    1993-01-01

    A set of vectors possessing the genes for aspartate semialdehyde dehydrogenase (asd) and the B subunit of the heat-labile enterotoxin of Escherichia coli (LT-B) has been developed. These vectors allow operon or gene fusions of foreign gene epitopes at the C-terminal end of LT-B. Two groups of vectors have been constructed with and without leader sequences to facilitate placing of the foreign antigen in different cell compartments. Two Streptococcus sobrinus genes coding for principal colonization factors, surface protein antigen A (SpaA), and dextranase (Dex), have been fused into the 3' end of the LT-B gene. Resulting protein fusions of approximately 120 to 130 kDa are extremely well recognized by antibodies directed against both SpaA and Dex as well as against LT-B domains and retain the enzymatic activity of dextranase and the biological activity of LT-B in that they bind to GM1 gangliosides. Maximum antigenicity was obtained with the vector possessing an intervening linker of at least six amino acids with two proline residues. Some of the fusion proteins also exhibited another property of LT-B in that they were exported into the periplasm where they oligomerized. LT-B-SpaA and LT-B-Dex hybrid proteins are expressed stably and at a high level in avirulent Salmonella typhimurium vaccine strains which are being used to investigate their immunogenicity and types of induced immune responses. The fusion vectors will also be useful for production and purification of LT-B fusion antigens to be used and evaluated in other vaccine compositions. Images PMID:8432584

  20. Biology of Attenuated Modified Vaccinia Virus Ankara Recombinant Vector in Mice: Virus Fate and Activation of B- and T-Cell Immune Responses in Comparison with the Western Reserve Strain and Advantages as a Vaccine

    PubMed Central

    Ramírez, Juan C.; Gherardi, M. Magdalena; Esteban, Mariano

    2000-01-01

    The modified vaccinia virus Ankara (MVA) strain is a candidate vector for vaccination against pathogens and tumors, due to safety concerns and the proven ability of recombinants based on this vector to trigger protection against pathogens in animals. In this study we addressed the fate of the MVA vector in BALB/c mice after intraperitoneal inoculation in comparison with that of the replication-competent Western Reserve (WR) strain by measuring levels of expression of the reporter luciferase gene, the capability to infect target tissues from the site of inoculation, and the length of time of virus persistence. We evaluated the extent of humoral and cellular immune responses induced against the virus antigens and a recombinant product (?-galactosidase). We found that MVA infects the same target tissues as the WR strain; surprisingly, within 6 h postinoculation the levels of expression of antigens were higher in tissues from MVA-infected mice than in tissues from mice infected with wild-type virus but at later times postinoculation were 2 to 4 log units higher in tissues from WR-infected mice. In spite of this, antibodies and cellular immune responses to viral vector antigens were considerably lower in MVA-inoculated mice than in WR virus-inoculated mice. In contrast, the cellular immune response to a foreign antigen expressed from MVA was similar to and even higher than that triggered by the recombinant WR virus. MVA elicited a Th1 type of immune response, and the main proinflammatory cytokines induced were interleukin-6 and tumor necrosis factor alpha. Our findings have defined the biological characteristics of MVA infection in tissues and the immune parameters activated in the course of virus infection. These results are of significance with respect to optimal use of MVA as a vaccine. PMID:10623755

  1. Vaccines against malaria.

    PubMed

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

  2. Biological risks associated with consumption of reptile products.

    PubMed

    Magnino, Simone; Colin, Pierre; Dei-Cas, Eduardo; Madsen, Mogens; McLauchlin, Jim; Nöckler, Karsten; Maradona, Miguel Prieto; Tsigarida, Eirini; Vanopdenbosch, Emmanuel; Van Peteghem, Carlos

    2009-09-15

    The consumption of a wide variety of species of reptiles caught from the wild has been an important source of protein for humans world-wide for millennia. Terrapins, snakes, lizards, crocodiles and iguanas are now farmed and the consumption and trade of their meat and other edible products have recently increased in some areas of the world. Biological risks associated with the consumption of products from both farmed and wild reptile meat and eggs include infections caused by bacteria (Salmonella spp., Vibrio spp.), parasites (Spirometra, Trichinella, Gnathostoma, pentastomids), as well as intoxications by biotoxins. For crocodiles, Salmonella spp. constitute a significant public health risk due to the high intestinal carrier rate which is reflected in an equally high contamination rate in their fresh and frozen meat. There is a lack of information about the presence of Salmonella spp. in meat from other edible reptilians, though captive reptiles used as pets (lizards or turtles) are frequently carriers of these bacteria in Europe. Parasitic protozoa in reptiles represent a negligible risk for public health compared to parasitic metazoans, of which trichinellosis, pentastomiasis, gnathostomiasis and sparganosis can be acquired through consumption of contaminated crocodile, monitor lizard, turtle and snake meat, respectively. Other reptiles, although found to harbour the above parasites, have not been implicated with their transmission to humans. Freezing treatment inactivates Spirometra and Trichinella in crocodile meat, while the effectiveness of freezing of other reptilian meat is unknown. Biotoxins that accumulate in the flesh of sea turtles may cause chelonitoxism, a type of food poisoning with a high mortality rate in humans. Infections by fungi, including yeasts, and viruses widely occur in reptiles but have not been linked to a human health risk through the contamination of their meat. Currently there are no indications that natural transmissible spongiform encephalopathies (TSEs) occur in reptilians. The feeding of farmed reptiles with non-processed and recycled animal products is likely to increase the occurrence of biological hazards in reptile meat. Application of GHP, GMP and HACCP procedures, respectively at farm and slaughterhouse level, is crucial for controlling the hazards. PMID:19679367

  3. Effects of vaccination with F-strain Mycoplasma gallisepticum on egg production and quality parameters of commercial layer hens previously vaccinated with 6/85-strain Mycoplasma gallisepticum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An experiment was conducted to determine the effect of overlaying (revaccinating) F strain Mycoplasma gallisepticum (MG) at 22 or 45 weeks of age on commercial leghorn hens previously vaccinated with 6/85 strain MG at 10 weeks of age. The treatment groups include unvaccinated hens (group 1), hens r...

  4. Future directions for the development of Chlamydomonas-based vaccines.

    PubMed

    Rosales-Mendoza, Sergio

    2013-09-01

    Besides serving as a valuable model in biological sciences, Chamydomonas reinhardtii has been used during the last decade in the biotechnology arena to establish models for the low cost production of vaccines. Antigens from various pathogens including Plasmodium falciparum, foot and mouth disease virus, Staphylococcus aureus, classical swine fever virus (CSFV) as well as some auto-antigens, have been produced in C. reinhardtii. Although some of them have been functionally characterized with promising results, this review identifies future directions for the advancement in the exploitation of this robust and safe vaccine production platform. The present analysis reflects that important immunological implications exist for this system and remain unexplored, including the possible adjuvant effects of algae biomolecules, the effect of bioencapsulation on immunogenicity and the possible development of whole-cell vaccines as an approach to trigger cytotoxic immune responses. Recently described molecular strategies that aim to optimize the expression of nuclear-encoded target antigens are also discussed. PMID:24053395

  5. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ...Notice of Meeting AGENCY: Food and Drug Administration, HHS...public advisory committee of the Food and Drug Administration (FDA...Evaluation and Research (HFM-71), Food and Drug Administration, 1401...appropriate advisory committee hot line/phone line to learn...

  6. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of...

  7. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of...

  8. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of...

  9. 77 FR 26162 - Amendments to Sterility Test Requirements for Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-03

    ...FDA-2011-N-0080] Amendments to Sterility Test Requirements for Biological Products AGENCY...Administration (FDA) is amending the sterility test requirements for biological products...appropriate and state-of- the-art test methods for assuring the safety of...

  10. 76 FR 36019 - Amendments to Sterility Test Requirements for Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ...FDA-2011-N-0080] Amendments to Sterility Test Requirements for Biological Products AGENCY...FDA) proposes to amend the sterility test requirements for biological products...appropriate and state-of- the-art test methods for assuring the safety of...

  11. Vaccine Finder

    MedlinePLUS

    ... Vaccine Information Statement for Shingles . Tetanus, Diphtheria, Whooping Cough (Tdap) Protects against whooping cough (pertussis), a very ... Vaccine Information Statement for Td . Tetanus, Diphtheria, Whooping Cough Tetanus, Diphtheria, Whooping Cough (Tdap) Protects against whooping ...

  12. Smallpox Vaccine

    MedlinePLUS

    ... outbreak of the disease. In most cases, the vaccine causes mild side effects, such as soreness around the vaccination site, fever, and body aches. A very small percentage of people will suffer serious side effects and may even die. Thus the vaccine is only necessary when there has been an ...

  13. Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases.

    PubMed

    Altenburg, Arwen F; Kreijtz, Joost H C M; de Vries, Rory D; Song, Fei; Fux, Robert; Rimmelzwaan, Guus F; Sutter, Gerd; Volz, Asisa

    2014-07-01

    Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses. PMID:25036462

  14. Effects of Taishan Pinus massoniana pollen polysaccharide on immune response of rabbit haemorrhagic disease tissue inactivated vaccine and on production performance of Rex rabbits.

    PubMed

    Wei, Kai; Sun, Zhenhong; Yan, Zhengui; Tan, Yanling; Wang, Hui; Zhu, Xiaolin; Wang, Xinjian; Sheng, Pengcheng; Zhu, Ruiliang

    2011-03-21

    Varied doses of Taishan Pinus massoniana pollen polysaccharide (TPPPS) and Astragalus polysaccharide (APS) extracted by hot water extraction and ethanol precipitation method were added to the vaccine in order to prepare polysaccharide-rabbit haemorrhagic disease (RHD) tissue inactivated vaccine. The purpose was to study effects of TPPPS on immune response of RHD tissue inactivated vaccine and on production performance of Rex rabbits. Results showed that each index in groups I, II, III and IV was higher than that in group V, especially groups I, II and IV, the difference between which and group V was much more significant (P<0.05); each index in group I was extremely higher than that in group V (P<0.01); each index in group I was significantly higher than that in groups II, III (P<0.05), and generally no significant difference was observed between groups II and III. The overall level in group IV was slightly lower than that in group I. Each index in the polysaccharide groups reached its peak value later than that in the non-polysaccharide groups did. Results suggested that any dose of TPPPS can enhance immunologic function and production performance of rabbits, and the amount of 400mg per rabbit has the most obvious efficacy. Furthermore, it can extend the immune peak period of RHD tissue inactivated vaccine and the growing peak period of Rex rabbits. TPPPS has generally higher efficiency than APS. PMID:21295100

  15. The case for a rational genome-based vaccine against malaria

    PubMed Central

    Proietti, Carla; Doolan, Denise L.

    2015-01-01

    Historically, vaccines have been designed to mimic the immunity induced by natural exposure to the target pathogen, but this approach has not been effective for any parasitic pathogen of humans or complex pathogens that cause chronic disease in humans, such as Plasmodium. Despite intense efforts by many laboratories around the world on different aspects of Plasmodium spp. molecular and cell biology, epidemiology and immunology, progress towards the goal of an effective malaria vaccine has been disappointing. The premise of rational vaccine design is to induce the desired immune response against the key pathogen antigens or epitopes targeted by protective immune responses. We advocate that development of an optimally efficacious malaria vaccine will need to improve on nature, and that this can be accomplished by rational vaccine design facilitated by mining genomic, proteomic and transcriptomic datasets in the context of relevant biological function. In our opinion, modern genome-based rational vaccine design offers enormous potential above and beyond that of whole-organism vaccines approaches established over 200 years ago where immunity is likely suboptimal due to the many genetic and immunological host-parasite adaptations evolved to allow the Plasmodium parasite to coexist in the human host, and which are associated with logistic and regulatory hurdles for production and delivery. PMID:25657640

  16. The case for vaccines.

    PubMed

    Hoffman, Wendell W

    2013-01-01

    The case for vaccines is one which has been made through scientific advancement and public health implementation, resulting in one of the most significant historical achievements for mankind. This includes the elimination of endemic smallpox, polio, measles and rubella from the U.S. This exhilarating accomplishment was sobered with the threat of smallpox through biological attack following September 11, 2001. While the unthinkable return of that vaccine-preventable disease never materialized, other vaccine-preventable disease, such as pertussis, have markedly increased in many states because of never-established or waning immunity. Drivers of these current threats come both from the anti-vaccine movement, through legislative efforts to expand childhood immunization exemptions and the medical establishment itself through lack of immunization prioritization in adolescent and adult populations. Therefore, the case for vaccines needs to be made both externally and internally through sound science, sound logic and sound ethics. Most powerfully, however, the case for vaccines is told through stories of real people who have suffered or died from these preventable diseases. PMID:23444585

  17. The hemoglobins of the trematodes Fasciola hepatica and Paramphistomum epiclitum: A molecular biological, physico-chemical, kinetic, and vaccination study

    PubMed Central

    Dewilde, Sylvia; Ioanitescu, A. Iulia; Kiger, Laurent; Gilany, Kambiz; Marden, Michael C.; Van Doorslaer, Sabine; Vercruysse, Jozef; Pesce, Alessandra; Nardini, Marco; Bolognesi, Martino; Moens, Luc

    2008-01-01

    The trematode Fasciola hepatica (Fa.he.) is a common parasite of human and livestock. The hemoglobin (Hb) of Fa.he., a potential immunogen, was chosen for characterization in the search for an effective vaccine. Characterization of trematode Hbs show that they are intracellular single-domain globins with the following remarkable features: (1) Fa.he. expresses two Hb isoforms that differ at two amino acid sites (F1: 119Y/123Q; F2: 119F/123L). Both isoforms are monoacetylated at their N-termini; (2) the genes coding for Fa.he. and Paramphistomum epiclitum (Pa.ep.) Hbs are interrupted by two introns at the conserved positions B12.2 and G7.0.; (3) UV/VIS and resonance Raman spectroscopy identify the recombinant Fa.he. HbF2 as a pentacoordinated high-spin ferrous Hb; (4) electron paramagnetic resonance spectroscopy of cyano-met Fa.he. HbF2 proves that the endogenously bound imidazole has no imidazolate character; (5) the major structural determinants of the globin fold are present, they contain a TyrB10/TyrE7 residue pair on the distal side. Although such distal-site pair is a signature for high oxygen affinity, as shown for Pa.ep. Hb, the oxygen-binding rate parameters for Fa.he. Hb are intermediate between those of myoglobin and those of other trematode Hbs; (6) the three-dimensional structure of recombinant Fa.he. HbF2 from this study closely resembles the three-dimensional structure of Pa.ep. determined earlier. The set of distal-site polar interactions observed in Pa.ep. Hb is matched with small but significant structural adjustments; (7) despite the potential immunogenic character of the fluke Hb, vaccination of calves with recombinant Fa.he. HbF2 failed to promote protection against parasitic infection. PMID:18621914

  18. Complete List of Vaccines Licensed for Immunization and Distributed in the U.S.

    MedlinePLUS

    ... A. Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) & Hepatitis B Vaccine (Recombinant) Comvax Merck & Co, Inc Hepatitis A Vaccine, ... and Hepatitis B (Recombinant) Vaccine Twinrix GlaxoSmithKline Biologicals Hepatitis B Vaccine (Recombinant) Recombivax HB Merck & Co, Inc Hepatitis B ...

  19. Nanoparticles for transcutaneous vaccination

    PubMed Central

    Hansen, Steffi; Lehr, Claus?Michael

    2012-01-01

    Summary The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano?vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle?free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra?flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed. PMID:21854553

  20. Making vaccines “on demand”

    PubMed Central

    De Groot, Anne S; Einck, Leo; Moise, Leonard; Chambers, Michael; Ballantyne, John; Malone, Robert W; Ardito, Matthew; Martin, William

    2013-01-01

    The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of “novel pathogens” such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process—from genome to gene sequence, ready to insert in a DNA plasmid—can now be accomplished in less than 24 h. While these vaccines are by no means “standard,” the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard. PMID:23877094

  1. Use of products of biological mineralization for cultivation of higher and lower autotrophs

    NASA Technical Reports Server (NTRS)

    Tsitovich, S. I.; Tsvetkova, I. V.; Belyakova, M. I.; Varlamov, V. F.; Zamota, V. P.; Maksimova, Y. V.; Chernovich, I. L.; Faleyeva, V. N.

    1973-01-01

    Data on the use of products of the vital functions of man which are mineralized by a biological method are reported. On the basis of these products nutrient solutions are made and subjected to biological tests using lime and higher autotrophs. Results show that the productiveness of the test plan does not differ from the control variants; the nutrient mixtures do not contain toxic substances, which means that they could be used with adjustments for cultivating higher and lower plants.

  2. Comparison of toxicities of acellular pertussis vaccine with whole cell pertussis vaccine in experimental animals.

    PubMed

    Sato, Y; Sato, H

    1991-01-01

    There is no suitable animal model for pertussis encephalopathy in humans. In this study, we have compared the toxicity of acellular pertussis vaccine with whole cell pertussis vaccine in mice or guinea pigs. Two lots of acellular and two lots of whole cell vaccine produced in different countries were assayed in the test. 1. There was no statistical difference in mouse protective potency between these acellular or whole cell pertussis vaccines. 2. There were no differences in chemical ingredients between acellular and whole cell pertussis vaccines except for protein nitrogen content. The protein nitrogen content of whole cell vaccine was at least three times higher than that of the acellular product. 3. Anti-PT antibody productivity of the acellular vaccine was higher than that of the whole cell vaccine. 4. Anti-agglutinogen antibody productivity of the whole cell vaccine was higher than that of the acellular vaccine. 5. There was no pyrogenic activity with the acellular vaccine, but high pyrogenicity was seen with whole cell vaccine. 6. There was high body-weight decreasing toxicity in mice and guinea pigs by the whole cell vaccine. 7. The mice died when they received whole cell pertussis vaccine iv, but no deaths occurred in the mice which received acellular pertussis vaccine. PMID:1778317

  3. Volatilization and efflux of mercury from biologically productive ocean regions

    SciTech Connect

    Kim, J.P.

    1987-01-01

    Mercury volatilization and oceanic evasion to the atmosphere were investigated in the tropical Pacific Ocean with emphasis on the biologically productive equatorial region. Further studies were conducted at two stations in the oligiotrophic North Pacific gyre, and in the estuarine mesocosms at the Marine Ecosystems Research Laboratory (MERL), University of Rhode Island. Dissolved gaseous Hg (DGM) in the tropical Pacific along 150/degree/ W at 4 stations ranged from 35-85 femtomoles per liter (fM) in surface waters and from 105-185 fM in deeper waters. Speciation experiments indicated that Hg/degree/was the dominant form in surface waters, while evidence for (CH/sub 3/)/sub 2/Hg was found at depth. In equatorial Pacific surface waters, DGM varied between 60 and 225 fM. Elemental Hg appears to comprise the major fraction of DGM. Elevated DGM concentrations corresponded with increased chlorophyll a levels and cooler, nutrient-rich waters. Surface waters of the equatorial Pacific were supersaturated with respect to Hg/degree/. Local Hg effluxes, estimated with a thin-film gas exchange model, were between 225 and 1050 pmoles/m/sup 2/ day. The annual Hg efflux from the equatorial Pacific, 1.6 /+-/ 1.3 /times/ 10/sup +6/ moles, was estimated at 4-5% of the total global Hg flux to the atmosphere. Dissolved gaseous Hg in the MERL mesocosms ranged from less than or equal to30 to 185 fM. In general, Hg/degree/ was the principal species, although (CH/sub 3/)/sub 2/minus// Hg was detected twice. Supersaturated levels of Hg/degrees/ corresponded with phytoplankton blooms of Cerataulina pelagica, Leptocylindrus danicus, Leptocylindrus mimimus, and Phaeocystis poucheti, suggesting that these phytoplankton could volatilize Hg in estuarine waters.

  4. Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses

    PubMed Central

    Mooney, Alaina J; Tompkins, S Mark

    2013-01-01

    Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches. PMID:23440999

  5. Future of Polio Vaccines

    PubMed Central

    2009-01-01

    Summary Over the past half-century, global use of highly effective vaccines against poliomyelitis brought this disease to the brink of elimination. Mounting evidence argues that a high level of population immunity must be maintained to preserve a polio-free status of the entire world after wild poliovirus circulation is stopped. Shifting factors in the risk-benefit-cost equation favor the creation of new poliovirus vaccines to be used in the foreseeable future. Genetically stable attenuated virus strains could be developed for an improved oral poliovirus vaccine, but proving their safety and efficacy would be impractical because of the enormous size of the clinical trials required. New versions of inactivated poliovirus vaccine (IPV) that could be used globally should be developed. An improved IPV must be efficacious, inexpensive, safe to manufacture, and easy to administer. Combination products containing IPV along with other protective antigens should become part of routine childhood immunizations around the world. PMID:19545205

  6. New tools for NTD vaccines: A case study of quality control assays for product development of the human hookworm vaccine Na-APR-1M74.

    PubMed

    Pearson, Mark S; Jariwala, Amar R; Abbenante, Giovanni; Plieskatt, Jordan; Wilson, David; Bottazzi, Maria Elena; Hotez, Peter J; Keegan, Brian; Bethony, Jeffrey M; Loukas, Alex

    2015-05-01

    Na-APR-1M74 is an aspartic protease that is rendered enzymatically inactive by site-directed mutagenesis and is a candidate antigen component in the Human Hookworm Vaccine. The mutant protease exerts vaccine efficacy by inducing antibodies that neutralize the enzymatic activity of wild type enzyme (Na-APR-1wt) in the gut of the hookworm, thereby depriving the worm of its ability to digest its blood meal. Previously, canines immunized with Na-APR-1M74 and challenged with Ancylostoma caninum were partially protected against hookworm challenge infection, especially from the loss in hemoglobin observed in control canines and canine immunoglobulin (Ig) G raised against Na-APR-1 was shown to inhibit the enzymatic activity of Na-APR-1wt in vitro, thereby providing proof of concept of Na-APR-1M74 as a vaccine antigen. The mutated version, Na-APR-1M74, was then expressed at the cGMP level using a Nicotiana benthamiana expression system (Fraunhofer, CMB, Delaware, MD), formulated with Alhydrogel®, and used to immunize mice in a dose-ranging study to explore the enzyme-neutralizing capacity of the resulting anti- Na-APR-1M74 IgG. As little as 0.99 ?g of recombinant Na-APR-1M74 could induce anti Na-APR-1M74 IgG in mice that were capable of inhibiting Na-APR-1wt-mediated digestion of a peptide substrate by 89%. In the absence of enzymatic activity of Na-APR-1M74 as a surrogate marker of protein functionality, we developed an assay based on the binding of a quenched fluorescence-labeled inhibitor of aspartic proteases, BODIPY-FL pepstatin A (BDP). Binding of BDP in the active site of Na-APR-1wt was demonstrated by inhibition of enzymatic activity, and competitive binding with unlabelled pepstatin A. BDP also bound to Na-APR-1M74 which was assessed by fluorescence polarization, but with an ?50-fold reduction in the dissociation constant. Taken together, these assays comprise a "toolbox" that could be useful for the analyses of Na-APR-1M74 as it proceeds through the clinical development as part of the Human Hookworm Vaccine pipeline. PMID:26018444

  7. Plant-derived virus-like particles as vaccines.

    PubMed

    Chen, Qiang; Lai, Huafang

    2013-01-01

    Virus-like particles (VLPs) are self-assembled structures derived from viral antigens that mimic the native architecture of viruses but lack the viral genome. VLPs have emerged as a premier vaccine platform due to their advantages in safety, immunogenicity, and manufacturing. The particulate nature and high-density presentation of viral structure proteins on their surface also render VLPs as attractive carriers for displaying foreign epitopes. Consequently, several VLP-based vaccines have been licensed for human use and achieved significant clinical and economical success. The major challenge, however, is to develop novel production platforms that can deliver VLP-based vaccines while significantly reducing production times and costs. Therefore, this review focuses on the essential role of plants as a novel, speedy and economical production platform for VLP-based vaccines. The advantages of plant expression systems are discussed in light of their distinctive posttranslational modifications, cost-effectiveness, production speed, and scalability. Recent achievements in the expression and assembly of VLPs and their chimeric derivatives in plant systems as well as their immunogenicity in animal models are presented. Results of human clinical trials demonstrating the safety and efficacy of plant-derived VLPs are also detailed. Moreover, the promising implications of the recent creation of "humanized" glycosylation plant lines as well as the very recent approval of the first plant-made biologics by the U. S. Food and Drug Administration (FDA) for plant production and commercialization of VLP-based vaccines are discussed. It is speculated that the combined potential of plant expression systems and VLP technology will lead to the emergence of successful vaccines and novel applications of VLPs in the near future. PMID:22995837

  8. 75 FR 11174 - Pesticide Product Registration Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ...Immunocontraceptive Vaccine containing an active ingredient not included...Immunocontraceptive Vaccine, contraceptive...03% active ingredient. This product...Immunocontraceptive Vaccine contraceptive...for this active ingredient one comment...

  9. Vaccine allergies

    PubMed Central

    2014-01-01

    Currently, the increasing numbers of vaccine administrations are associated with increased reports of adverse vaccine reactions. Whilst the general adverse reactions including allergic reactions caused by the vaccine itself or the vaccine components, are rare, they can in some circumstances be serious and even fatal. In accordance with many IgE-mediated reactions and immediate-type allergic reactions, the primary allergens are proteins. The proteins most often implicated in vaccine allergies are egg and gelatin, with perhaps rare reactions to yeast or latex. Numerous studies have demonstrated that the injectable influenza vaccine can be safely administered, although with appropriate precautions, to patients with severe egg allergy, as the current influenza vaccines contain small trace amounts of egg protein. If an allergy is suspected, an accurate examination followed by algorithms is vital for correct diagnosis, treatment and decision regarding re-vaccination in patients with immediate-type reactions to vaccines. Facilities and health care professionals should be available to treat immediate hypersensitivity reactions (anaphylaxis) in all settings where vaccines are administered. PMID:24427763

  10. Vaccine Design: Emerging Concepts and Renewed Optimism

    PubMed Central

    Grimm, Sebastian K.; Ackerman, Margaret E.

    2013-01-01

    Arguably, vaccination represents the single most effective medical intervention ever developed. Yet, vaccines have failed to provide any or adequate protection against some of the most significant global diseases. The pathogens responsible for these vaccine-recalcitrant diseases have properties that allow them to evade immune surveillance and misdirect or eliminate the immune response. However, genomic and systems biology tools, novel adjuvants and delivery systems, and refined molecular insight into protective immunity have started to redefine the landscape, and results from recent efficacy trials of HIV and malaria vaccines have instilled hope that another golden age of vaccines may be on the horizon. PMID:23474232

  11. Expression of Recombinant Vaccines and Antibodies in Plants

    PubMed Central

    2014-01-01

    Plants are able to perform post-translational maturations of therapeutic proteins required for their functional biological activity and suitable in vivo pharmacokinetics. Plants can be a low-cost, large-scale production platform of recombinant biopharmaceutical proteins such as vaccines and antibodies. Plants, however, lack mechanisms of processing authentic human N-glycosylation, which imposes a major limitation in their use as an expression system for therapeutic glycoproducts. Efforts have been made to circumvent plant-specific N-glycosylation, as well as to supplement the plant's endogenous system with human glycosyltransferases for non-immunogenic and humanized N-glycan production. Herein we review studies on the potential of plants to serve as production systems for therapeutic and prophylactic biopharmaceuticals. We have especially focused on recombinant vaccines and antibodies and new expression strategies to overcome the existing problems associated with their production in plants. PMID:24937251

  12. Why Reduced Seed Production is Not Necessarily Translated Into Successful Biological Weed Control

    Microsoft Academic Search

    J. H. MYERS; CHRISTOPHER RISLEY

    Insects introduced as biological control agents of diffuse knapweed, Centaurea dif- fusa, primarily reduce seed production. Knapweed densities appear to be resilient to great- ly reduced seed production. We have used measurements of seedling density and survival, and production of seeds by flowering diffuse knapweed plants to develop functions for a model of knapweed populations. These simulations show that improved

  13. BENEFICIAL USE OF ATTENUATED VACCINES IN AQUACULTURE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The success of safe and effective vaccines in controlling disease and enhancing profitability in livestock production has been profound. Because fish farmers operate on narrow profit margins, cost effectiveness is of paramount importance in any vaccination program. In aquaculture, the best vaccines ...

  14. Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages.

    PubMed

    Kramberger, Petra; Urbas, Lidija; Štrancar, Aleš

    2015-04-01

    Downstream processing of nanoplexes (viruses, virus-like particles, bacteriophages) is characterized by complexity of the starting material, number of purification methods to choose from, regulations that are setting the frame for the final product and analytical methods for upstream and downstream monitoring. This review gives an overview on the nanoplex downstream challenges and chromatography based analytical methods for efficient monitoring of the nanoplex production. PMID:25751122

  15. Influenza vaccination in oncology patients.

    PubMed

    Baluch, Aliyah; Pasikhova, Yanina

    2013-12-01

    It is well established that the immunological response to the seasonal trivalent influenza vaccine is attenuated in cancer patients. Furthermore, rates of seroprotection and seroconversion vary by malignancy type and are higher in patients with solid tumors, as compared either with those with hematologic malignancies or with allogeneic hematopoietic stem cell recipients. In 2009, a novel influenza strain prompted development of new vaccines and evaluation of alternative dosing strategies in an attempt to increase the rates of seroconversion in immunocompromised patients, further complicating this issue. Recent literature has demonstrated that the use of myeloablative chemotherapy regimens and biologics is correlated with decreased immunogenicity and response to influenza vaccines. Much debate still exists as to the optimal timing of influenza vaccination. Delaying vaccination from 1 week following standard chemotherapy up to 6 months following rituximab is increasingly supported by studies in this heterogeneous population. PMID:24258350

  16. Forty years of canine vaccination.

    PubMed

    Appel, M J

    1999-01-01

    During the last 40 years vaccines have been developed that have greatly reduced the incidence of infectious diseases of dogs. In general, modified live products have been superior to inactivated vaccines for dogs. It can be expected that recombinant and/or DNA vaccines may dominate the market in the future. Although most vaccines on the market are safe and efficacious, there have been exceptions where disease was induced by vaccination or dogs were not protected. The failure of protection may in part be due to variations in individual vaccine batches. Only potency tests but not efficacy tests are required, which may not be sufficient. For example, a virus titer in a vaccine may be meaningless if the minimum protective dose is not known. Overattenuated virus (e.g., CDV-Ond or parvovirus in cat cells) may have a high titer in tissue culture but is not immunogenic. The question of frequency of vaccination of dogs should be addressed. Annual revaccinations for CDV, CPV, and CAV are probably not needed. However, it would be desirable to collect more data to support less frequent vaccinations. Annual immunization for bacterial diseases such as kennel cough, Lyme disease, and leptospirosis should continue. It also would be desirable to develop more oro/nasal vaccines, perhaps combined with newly developed vectors that are less likely to induce undesirable side effects that may be seen after parenteral vaccination. Finally a word of warning against homeopathic "nosodes" to replace tested canine vaccines. They will appear highly effective as long as the majority of dogs remain vaccinated. As soon as a nonvaccinated dog population is large enough to allow virulent agents to spread, disease outbreaks will occur and we will be back where we began 40 years ago. PMID:9890024

  17. The glycoprotein products of varicella-zoster virus gene 14 and their defective accumulation in a vaccine strain (Oka).

    PubMed

    Kinchington, P R; Ling, P; Pensiero, M; Moss, B; Ruyechan, W T; Hay, J

    1990-09-01

    Many characteristics of the putative protein encoded by varicella-zoster virus (VZV) open reading fram (ORF) 14 indicate that it is a glycoprotein, which has been designated gpV. To identify the protein products of the gene, the coding sequences were placed under the control of the vaccinia virus p7.5 promoter and recombinant vaccinia viruses were constructed. Heterogeneous polypeptides with molecular weights of 95,000 to 105,000 (95K to 105K polypeptides) were expressed in cells infected by a vaccinia virus recombinant (vKIP5) containing ORF 14 from VZV Scott but were not expressed by control vaccinia viruses. These polypeptides were recognized by antibodies present in human sera that contained high levels of anti-VZV antibodies. Conversely, antisera raised in rabbits inoculated with vKIP5 reacted specifically with heterogeneous 95K to 105K polypeptides present in VZV Scott-infected but not uninfected cells; these polypeptides show a patchy plasma membrane fluorescence pattern in VZV Scott-infected cells. These same antisera neutralized VZV strain Scott infectivity in the absence of complement. Endoglycosidase F treatment of isolated gpV polypeptides and tunicamycin treatment of cells infected with the vKIP5 recombinant indicated that the polypeptides were glycosylated. Three sets of data imply that the VZV strain Oka, which has been used to produce a live attenuated virus vaccine, accumulates low levels of gpV polypeptides relative to wild-type strains: (i) blocking of antibodies in human sera with excess VZV Oka-infected cell antigen yielded residual antibodies which were reactive with the 95K to 105K gpV polypeptides expressed in cells infected by VZV strain Scott and by the vKIP5 vaccinia virus recombinant, but not with Oka-infected cell polypeptides; (ii) antisera raised to vKIP5 detected very low levels of reactive polypeptides made in VZV Oka-infected cells and neutralized VZV Oka virus much less efficiently than VZV Scott; and (iii) comparisons of the reactivity of sera from live attenuated virus vaccine vaccinees with sera derived from patients recovering from wild-type infections indicated greatly reduced levels of gpV-specific antibodies in some vaccinees. PMID:2166829

  18. 78 FR 65904 - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 20, 310, 314...Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products AGENCY: Food and Drug Administration, HHS. ACTION: Proposed...

  19. 75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 312 and 320 [Docket...00N-1484) RIN 0910-AG13 Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety...

  20. 78 FR 12760 - Guidance for Industry on Labeling for Human Prescription Drug and Biological Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0153...Industry on Labeling for Human Prescription Drug and Biological Products--Implementing...Requirements; Availability AGENCY: Food and Drug Administration, HHS. ACTION:...

  1. 78 FR 67985 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 314 and 601 [Docket...Applications Proposing Labeling Changes for Approved Drugs and Biological Products AGENCY: Food and Drug Administration, HHS. ACTION: Proposed...

  2. 9 CFR 113.53 - Requirements for ingredients of animal origin used for production of biologics.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...sterilization of other sterilization methods acceptable to APHIS used to prepare a biological product shall be shown free of bacteria and fungi as prescribed in § 113.26. (c) Samples of each lot of ingredient of animal origin, except porcine...

  3. BCG vaccination.

    PubMed

    Guerin, N; Bregere, P

    1992-01-01

    The practical elements of BCG vaccination in neonates are used in most developing countries are outlined. The World Health Organization that all neonates be vaccinated, as well as all unvaccinated children when they present for health care, without prior PPD testing. BCG vaccine is a live attenuated TB vaccine in lyophilized state, so it must be kept cold and away from light. After redissolving, the vaccine is given intradermally with a 0.45% 10 mm needle either on the volar left forearm or the posterior left arm, at a consistent site in each country. The dose must be 0.05 ml for babies 1 year old, and 0.1 ml for older children. A wheal is formed that disappears in 30 minutes, followed by a red nodule in 3-4 weeks. The depressed scar is evidence of vaccination. In rare cases, lymphadenitis may appear, sometimes with a fistula. This is more likely when 0,1 ml is given to infants, the vaccine is not diluted properly, or the injection is given too deeply. While immunodeficiency is considered a contraindication for BCG vaccination, infants born to HIV-positive mothers have received it without adverse effects. Other immunizations such as oral polio may be given concomitantly. Verification of BCG vaccination is by presence of the scar or PPD testing. About 30-50% of children entering school are still positive; negative children may be revaccinated. PMID:12345145

  4. [Vaccines pharmacovigilance].

    PubMed

    Autret-Leca, Elisabeth; Jonville-Béra, Annie-Pierre; Beau-Salinas, Frédérique

    2004-03-15

    The pharmacovigilance of vaccines has the particularity of concerning medications with a preventative target, used in healthy subjects, who are often young. Their individual benefit is deferred and unknown, whereas their risk is immediate. Certain undesirable effects are linked to the antigen of live attenuated vaccines (post-MMR lymphocytic meningitis). Other non-specific effects are linked to other different components of the vaccines (macrophage and aluminium myofasciitis). Undesirable events susceptible to being due to the vaccination are identified and managed according to standardised procedures of pharmacovigilance, that is to say, based on "spontaneous notification", generation of an alert, confirmed or not by studies of pharmaco-epidemiology. The studies of pharmaco-epidemiology: have made evident oedematous reactions with cyanosis or purpura, with the vaccines containing the Haemophilus b valence, and the absence of an association with sudden death of the newborn; have excluded the existence of an elevated risk of demyelinisation or auto-immune disease associated with vaccination against hepatitis B, without being able to exclude a slight risk; go against the finding of an association between Crohn's disease and/or autisim and the MMR vaccination. Only their frequently encountered undesirable effects are well identified at the moment of commercialisation. Post-marketing surveillance of vaccines (declaration to the regional pharmacovigilance centres) allow the detection of possible rare and serious effects and the evaluation of the real vaccination risk. Thus it must be intensive and systematic. PMID:15176512

  5. Advances in Antiviral vaccine development

    PubMed Central

    Graham, Barney S.

    2013-01-01

    Summary Antiviral vaccines have been the most successful biomedical intervention for preventing epidemic viral disease. Vaccination for smallpox in humans and rinderpest in cattle was the basis for disease eradication, and recent progress in polio eradication is promising. While early vaccines were developed empirically by passage in live animals or eggs, more recent vaccines have been developed because of the advent of new technologies, particularly cell culture and molecular biology. Recent technological advances in gene delivery and expression, nanoparticles, protein manufacturing, and adjuvants have created the potential for new vaccine platforms that may provide solutions for vaccines against viral pathogens for which no interventions currently exist. In addition, the technological convergence of human monoclonal antibody isolation, structural biology, and high throughput sequencing is providing new opportunities for atomic-level immunogen design. Selection of human monoclonal antibodies can identify immunodominant antigenic sites associated with neutralization and provide reagents for stabilizing and solving the structure of viral surface proteins. Understanding the structural basis for neutralization can guide selection of vaccine targets. Deep sequencing of the antibody repertoire and defining the ontogeny of the desired antibody responses can reveal the junctional recombination and somatic mutation requirements for B-cell recognition and affinity maturation. Collectively, this information will provide new strategic approaches for selecting vaccine antigens, formulations, and regimens. Moreover, it creates the potential for rational vaccine design and establishing a catalogue of vaccine technology platforms that would be effective against any given family or class of viral pathogens and improve our readiness to address new emerging viral threats. PMID:23947359

  6. Biological production of ethanol from waste gases with Clostridium ljungdahlii

    DOEpatents

    Gaddy, James L. (Fayetteville, AR)

    2000-01-01

    A method and apparatus for converting waste gases from industrial processes such as oil refining, carbon black, coke, ammonia, and methanol production, into useful products is disclosed. The method includes introducing the waste gases into a bioreactor where they are fermented to various product, such as organic acids, alcohols H.sub.2, SCP, and salts of organic acids by anaerobic bacteria within the bioreactor. These valuable end products are then recovered, separated and purified.

  7. Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

    PubMed

    Wang, Yali; Dong, Duo; Cheng, Gang; Zuo, Shuyan; Liu, Dawei; Du, Xiaoxi

    2014-10-01

    Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied. PMID:25173477

  8. Meningococcal vaccines.

    PubMed

    Rüggeberg, Jens U; Pollard, Andrew J

    2004-01-01

    Meningococcal disease is one of the most feared and serious infections in the young and its prevention by vaccination is an important goal. The high degree of antigenic variability of the organism makes the meningococcus a challenging target for vaccine prevention. Meningococcal polysaccharide vaccines against serogroup A and C are efficacious and have been widely used, often in combination with serogroup Y and W135 components. Their relative lack of immunogenicity in young children and infants can be overcome by conjugation to a protein carrier. The effectiveness of serogroup C glycoconjugate vaccines in children of all ages has been demonstrated and they have now been introduced into routine vaccination schedules. Conjugate vaccines against other serogroups, including A, Y, and W135 will soon be available and it is hoped they may emulate this success. Prevention of serogroup B disease has proven more elusive. Several serogroup B vaccines based on outer membrane vesicles have been shown to be immunogenic and reasonably effective in adults and older children, but the protection offered by them is chiefly strain-specific. Multivalent recombinant PorA vaccines have been developed to broaden the protective effect, but no efficacy data are available as yet. Intensive efforts have been directed at other outer membrane protein vaccine candidates and lipopolysaccharide, and some of these have been shown to offer protection in experimental animal models. Nonpathogenic Neisseriae spp. such as Neisseria lactamica are also possible vaccine candidates. Previously unknown proteins have been identified from in silico analysis of the meningococcal genome and their vaccine potential explored. However, none of these has yet been presented as the 'universal' protective antigen and work in this field continues to be held back by our limited knowledge concerning the mechanisms of natural protection against serogroup B meningococci. PMID:15339202

  9. Molecular and biological characterization of the 5 human-bovine rotavirus (WC3)-based reassortant strains of the pentavalent rotavirus vaccine, RotaTeq (registered)

    SciTech Connect

    Matthijnssens, Jelle [Laboratory of Clinical and Epidemiological Virology, Department of Microbiology and Immunology, Rega Research Institute for Medical Research, University of Leuven, Leuven (Belgium); Joelsson, Daniel B.; Warakomski, Donald J.; Zhou, Tingyi; Mathis, Pamela K.; Maanen, Marc-Henri van; Ranheim, Todd S. [Bioprocess and Bioanalytical Research, Merck Research Laboratories, North Wales, PA 19454 (United States); Ciarlet, Max, E-mail: max_ciarlet@merck.co [Vaccines-Clinical Research Department, Merck Research Laboratories, North Wales, PA 19454 (United States)

    2010-08-01

    RotaTeq (registered) is a pentavalent rotavirus vaccine that contains five human-bovine reassortant strains (designated G1, G2, G3, G4, and P1) on the backbone of the naturally attenuated tissue culture-adapted parental bovine rotavirus (BRV) strain WC3. The viral genomes of each of the reassortant strains were completely sequenced and compared pairwise and phylogenetically among each other and to human rotavirus (HRV) and BRV reference strains. Reassortants G1, G2, G3, and G4 contained the VP7 gene from their corresponding HRV parent strains, while reassortants G1 and G2 also contained the VP3 gene (genotype M1) from the HRV parent strain. The P1 reassortant contained the VP4 gene from the HRV parent strain and all the other gene segments from the BRV WC3 strain. The human VP7s had a high level of overall amino acid identity (G1: 95-99%, G2: 94-99% G3: 96-100%, G4: 93-99%) when compared to those of representative rotavirus strains of their corresponding G serotypes. The VP4 of the P1 reassortant had a high identity (92-97%) with those of serotype P1A[8] HRV reference strains, while the BRV VP7 showed identities ranging from 91% to 94% to those of serotype G6 HRV strains. Sequence analyses of the BRV or HRV genes confirmed that the fundamental structure of the proteins in the vaccine was similar to those of the HRV and BRV references strains. Sequences analyses showed that RotaTeq (registered) exhibited a high degree of genetic stability as no mutations were identified in the material of each reassortant, which undergoes two rounds of replication cycles in cell culture during the manufacturing process, when compared to the final material used to fill the dosing tubes. The infectivity of each of the reassortant strains of RotaTeq (registered) , like HRV strains, did not require the presence of sialic acid residues on the cell surface. The molecular and biologic characterization of RotaTeq (registered) adds to the significant body of clinical data supporting the consistent efficacy, immunogenicity, and safety of RotaTeq (registered) .

  10. Optimization and revision of the production process of the Necator americanus glutathione S-transferase 1 (Na-GST-1), the lead hookworm vaccine recombinant protein candidate.

    PubMed

    Curti, Elena; Seid, Christopher A; Hudspeth, Elissa; Center, Lori; Rezende, Wanderson; Pollet, Jeroen; Kwityn, Cliff; Hammond, Molly; Matsunami, Rise K; Engler, David A; Hotez, Peter J; Elena Bottazzi, Maria

    2014-01-01

    Infection by the human hookworm Necator americanus is a leading cause of anemia and disability in the developing countries of Africa, Asia, and the Americas. In order to prevent childhood hookworm disease in resource poor settings, a recombinant vaccine is under development by the Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, a Product Development Partnership (PDP). Previously, we reported on the expression and purification of a highly promising hookworm vaccine candidate, Na-GST-1, an N. americanus glutathione s-transferase expressed in Pichia pastoris (yeast), which led to production of 1.5 g of 95% pure recombinant protein at a 20L scale. (1) (,) (2) (,) (3) This yield and purity of Na-GST-1 was sufficient for early pilot manufacturing and initial phase 1 clinical testing. However, based on the number of doses which would be required to allow mass vaccination and a potential goal to deliver a vaccine as inexpensively as possible, a higher yield of expression of the recombinant antigen at the lowest possible cost is highly desirable. Here we report on modifications to the fermentation (upstream process) of the antigen expressed in P. pastoris, and to the purification (downstream process) of the recombinant protein that allowed for a 2-3-fold improvement in the final yield of Na-GST-1 purified protein. The major improvements included upstream process changes such as the addition of a sorbitol pulse and co-feed during methanol induction as well as an extension of the induction stage to approximately 96 hours; downstream process changes included modifying the UFDF to flat sheet with a 10 kDa Molecular Weight cut-off (MWCO), adjusting the capacity of an ion-exchange chromatography step utilizing a gradient elution as opposed to the original step elution, and altering the hydrophobic interaction chromatography conditions. The full process, as well as the purity and stability profiles of the target Na-GST-1, and its formulation on Alhydrogel(®), is described. PMID:25424799

  11. Optimization and revision of the production process of the Necator americanus glutathione S-transferase 1 (Na-GST-1), the lead hookworm vaccine recombinant protein candidate

    PubMed Central

    Curti, Elena; Seid, Christopher A; Hudspeth, Elissa; Center, Lori; Rezende, Wanderson; Pollet, Jeroen; Kwityn, Cliff; Hammond, Molly; Matsunami, Rise K; Engler, David A; Hotez, Peter J; Elena Bottazzi, Maria

    2014-01-01

    Infection by the human hookworm Necator americanus is a leading cause of anemia and disability in the developing countries of Africa, Asia, and the Americas. In order to prevent childhood hookworm disease in resource poor settings, a recombinant vaccine is under development by the Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, a Product Development Partnership (PDP). Previously, we reported on the expression and purification of a highly promising hookworm vaccine candidate, Na-GST-1, an N. americanus glutathione s-transferase expressed in Pichia pastoris (yeast), which led to production of 1.5 g of 95% pure recombinant protein at a 20L scale.1, 2, 3 This yield and purity of Na-GST-1 was sufficient for early pilot manufacturing and initial phase 1 clinical testing. However, based on the number of doses which would be required to allow mass vaccination and a potential goal to deliver a vaccine as inexpensively as possible, a higher yield of expression of the recombinant antigen at the lowest possible cost is highly desirable. Here we report on modifications to the fermentation (upstream process) of the antigen expressed in P. pastoris, and to the purification (downstream process) of the recombinant protein that allowed for a 2–3-fold improvement in the final yield of Na-GST-1 purified protein. The major improvements included upstream process changes such as the addition of a sorbitol pulse and co-feed during methanol induction as well as an extension of the induction stage to approximately 96 hours; downstream process changes included modifying the UFDF to flat sheet with a 10 kDa Molecular Weight cut-off (MWCO), adjusting the capacity of an ion-exchange chromatography step utilizing a gradient elution as opposed to the original step elution, and altering the hydrophobic interaction chromatography conditions. The full process, as well as the purity and stability profiles of the target Na-GST-1, and its formulation on Alhydrogel®, is described. PMID:25424799

  12. ATTENUATED VACCINES FOR EDWARDSIELLA ICTALURI AND FLAVOBACTERIUM COLUMNARE OF CATFISH

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prevention of fish diseases is becoming more dependent on the use of vaccines. An important consideration is what type of vaccine to use: attenuated or a killed vaccine? The choice of the vaccine needs to be compatible with production system and growth cycle of the fish species. Also, the choice ...

  13. IMPROVED PRODUCTION AND EFFICACY OF BIOLOGICAL CONTROL AGENTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to optimize the use of biological control agents in augmentative or inundative releases, it is necessary to have adequate numbers of high quality organisms that are well suited for the environment into which they will be released. For predators and parasites, this requires development of c...

  14. Silicon biotechnology: harnessing biological silica production to construct new materials

    Microsoft Academic Search

    Daniel E. Morse

    1999-01-01

    Silicon, the basis of semiconductors and many advanced materials, is an essential element for higher plants and animals, yet its biology is poorly understood. Many invertebrates produce exquisitely controlled silica structures with a nanoscale precision exceeding present human ability. Biotechnology is starting to reveal the proteins, genes and molecular mechanisms that control this synthesis in marine organisms that produce large

  15. Chemistry and Biology of Bengamides and Bengazoles, Bioactive Natural Products from Jaspis Sponges

    PubMed Central

    García-Ruiz, Cristina; Sarabia, Francisco

    2014-01-01

    Sponges corresponding to the Jaspidae family have proved to be a prolific source of bioactive natural products. Among these, the bengamides and the bengazoles stand out by virtue of their unprecedented molecular architectures and impressive biological profiles, including antitumor, antibiotic and anthelmintic properties. As a consequence, intense research activity has been devoted to these compounds from both chemical and biological standpoints. This review describes in detail the research into these classes of natural products and the benefits they offer in chemistry and biology. PMID:24646945

  16. Memory T cell proliferative responses and IFN-? productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

    PubMed Central

    2014-01-01

    Porcine circovirus type 2 (PCV2) vaccination represents an important measure to cope with PCV2 infection; however, data regarding the modulation of the immune cell compartment are still limited, especially under field conditions. This study is aimed at investigating the features of the cellular immune response in conventional piglets induced by vaccination using a capsid (Cap) protein-based PCV2 vaccine compared to unvaccinated animals when exposed to PCV2 natural infection. Immune reactivity was evaluated by quantifying peripheral cell subsets involved in the anti-viral response and characterizing the interferon-gamma (IFN-?) secreting cell (SC) responsiveness both in vivo and upon in vitro whole PCV2 recall. The vaccination triggered an early and intense IFN-? secreting cell response and induced the activation of peripheral lymphocytes. The early increase of IFN-? SC frequencies resulted in a remarkable and transient tendency to increased IFN-? productivity in vaccinated pigs. In vaccinated animals, soon before the onset of infection occurred 15-16 weeks post-vaccination, the recalled PCV2-specific immune response was characterized by moderate PCV2-specific IFN-? secreting cell frequencies and augmented productivity together with reactive CD4+CD8+ memory T cells. Conversely, upon infection, unvaccinated animals showed very high frequencies of IFN-? secreting cells and a tendency to lower productivity, which paralleled with effector CD4–CD8+ cytotoxic cell responsiveness. The study shows that PCV2 vaccination induces a long-lasting immunity sustained by memory T cells and IFN-? secreting cells that potentially played a role in preventing the onset of infection; the extent and duration of this reactivity can be an important feature for evaluating the protective immunity induced by vaccination. PMID:24735253

  17. Microneedle patches for vaccine delivery

    PubMed Central

    Suh, Hyemee; Shin, Juhyung

    2014-01-01

    In today's medical industry, the range of vaccines that exist for administration in humans represents an eclectic variety of forms and immunologic mechanisms. Namely, these are the live attenuated viruses, inactivated viruses, subunit proteins, and virus-like particles for treating virus-caused diseases, as well as the bacterial-based polysaccharide, protein, and conjugated vaccines. Currently, a new approach to vaccination is being investigated with the concept of DNA vaccines. As an alternative delivery route to enhance the vaccination efficacy, microneedles have been devised to target the rich network of immunologic antigen-presenting cells in the dermis and epidermis layers under the skin. Numerous studies have outlined the parameters of microneedle delivery of a wide range of vaccines, revealing comparable or higher immunogenicity to conventional intramuscular routes, overall level of stability, and dose-sparing advantages. Furthermore, recent mechanism studies have begun to successfully elucidate the biological mechanisms behind microneedle vaccination. This paper describes the current status of microneedle vaccine research. PMID:24427762

  18. Adult vaccination.

    PubMed

    Swanson, Kena A; Schmitt, H Josef; Jansen, Kathrin U; Anderson, Annaliesa S

    2015-01-01

    Vaccination of children has had a major impact on the morbidity and mortality of many infectious diseases globally. However, with age, immune responses to vaccines can be less robust, which can be further enhanced by underlying diseases that are common in the older adult. In many countries around the globe booster vaccinations against diphtheria, tetanus, and pertussis are recommended for adults. For the older adult, vaccination against pneumococcal diseases, influenza and herpes zoster are also recommended. Despite these recommendations, the widespread use of these vaccines in the adult population clearly lags behind the vaccine uptake and successes documented for pediatric vaccination programs. Furthermore, extensive and sometimes inappropriate use of antibiotics have fostered the emergence of antibiotic-resistant bacteria (e.g., methicillin resistant Staphylococcus aureus (MRSA)) as well as increased susceptibility in the elderly to bacterial species such as Clostridium difficile. Infectious diseases remain an important unmet medical need and new concepts to successfully implement vaccination of adults are urgently needed. PMID:25483533

  19. The International AIDS Vaccine Initiative (IAVI) in a Changing Landscape of Vaccine Development: A Public\\/Private Partnership as Knowledge Broker and Integrator

    Microsoft Academic Search

    Joanna Chataway; Stefano Brusoni; Eugenia Cacciatori; Rebecca Hanlin; Luigi Orsenigo

    2007-01-01

    Vaccine production is now at the heart of the debate on development. This paper argues that, as well as economic policies to address market failures, development policies aimed at fostering vaccine innovation should also consider the institutional and organisational uncertainties. The International Aids Vaccine Initiative (IAVI), a product development PPP, is attempting to increase vaccine production for neglected diseases by

  20. Therapeutic vaccination to treat chronic infectious diseases

    PubMed Central

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

    2012-01-01

    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

  1. Vaccines and infectious disease

    Microsoft Academic Search

    Mark A. Fletcher; Pierre Saliou

    \\u000a The exponential growth in vaccine research over the last decade, in which many infectious diseases now appear to be amenable\\u000a to prevention through immunization, is built upon three factors: first, a richer understanding of the immune response (in\\u000a particular, cellular immunity), second, a greater finesse in understanding the molecular biology of pathogenicity, and third,\\u000a an expanding use of genetic engineering

  2. Human megakaryocyte production: cell biology and clinical considerations.

    PubMed

    Gewirtz, A M; Hoffman, R

    1990-02-01

    Advances in the methodologic study of megakaryocytopoiesis are discussed, and their effect on the understanding of the production of platelets is included. This knowledge has led to a better understanding of disorders of megakaryocytopoiesis and platelet production. Specific diseases discussed are congenital megakaryocyte hypoplasia, acquired amegakaryocytic thrombocytopenic purpura, myeloproliferative disorders, reactive thrombocytosis, megakaryoblastic leukemia, and megakaryocyte and marrow fibrosis. PMID:2179214

  3. Kinetic study of biological hydrogen production by anaerobic fermentation

    Microsoft Academic Search

    Wen-Hsing Chen; Shen-Yi Chen; Samir Kumar Khanal; Shihwu Sung

    2006-01-01

    The growth kinetics of hydrogen producing bacteria using three different substrates, namely sucrose, non-fat dry milk (NFDM), and food waste were investigated in dark fermentation through a series of batch experiments. The results showed that hydrogen production potential and hydrogen production rate increased with an increasing substrate concentration. The maximum hydrogen yields from sucrose, NFDM, and food waste were 234,

  4. Biology Needs a Modern Assessment System for Professional Productivity

    ERIC Educational Resources Information Center

    McDade, Lucinda A.; Maddison, David R.; Guralnick, Robert; Piwowar, Heather A.; Jameson, Mary Liz; Helgen, Kristofer M.; Herendeen, Patrick S.; Hill, Andrew; Vis, Morgan L.

    2011-01-01

    Stimulated in large part by the advent of the Internet, research productivity in many academic disciplines has changed dramatically over the last two decades. However, the assessment system that governs professional success has not kept pace, creating a mismatch between modes of scholarly productivity and academic assessment criteria. In this…

  5. Evaluation of anthrax vaccine production by Bacillus anthracis Sterne 34F 2 in stirred suspension culture using a miniature bioreactor: A useful scale-down tool for studies on fermentations at high containment

    Microsoft Academic Search

    Tarit K. Mukhopadhyay; Nigel Allison; Susan Charlton; Michael J. Hudson; Bassam Hallis; Annemarie King; Rebecca Baker; Sara Noonan; Joanne McGlashan; Katie West; M. Susana Levy; John M. Ward; Gary J. Lye

    2010-01-01

    The licensed UK anthrax vaccine is produced by static cultures of Bacillus anthracis Sterne 34F2 in glass Thompson bottles, each batch consisting of multiple bottles grown for 24–28h. In this work, a novel miniature bioreactor was used as a scale-down tool to investigate the possible transfer of anthrax vaccine production from static culture to stirred tank operation and to explore

  6. Biochemical and biological characteristics of cross-reacting material 197 CRM197, a non-toxic mutant of diphtheria toxin: use as a conjugation protein in vaccines and other potential clinical applications.

    PubMed

    Bröker, Michael; Costantino, Paolo; DeTora, Lisa; McIntosh, E David; Rappuoli, Rino

    2011-07-01

    The biochemical and biological characteristics of CRM(197) are reviewed. Polysaccharide protein conjugate vaccines represent an important technological advancement that allowed for protection against dangerous diseases in vulnerable populations such as infants. The first carrier proteins, diphtheria and tetanus toxoids, were chosen in the context of an extensive body of information describing their immunogenicity and safety profiles in clinical use. These carriers perform well, and they require detoxification. A non-toxic mutant of diphtheria toxin, cross-reacting material 197 (CRM(197)), is a useful carrier protein with several manufacturing and other potential advantages over toxoids. For over a decade, several important and widely used routine childhood glycoconjugate vaccines against serious illnesses, including Haemophilus influenzae type b and pneumococcal disease, have employed CRM(197) as carrier protein. Additional clinical applications of CRM(197), as in chemotherapy, also exist. PMID:21715186

  7. Biological Production of Methane from Lunar Mission Solid Waste: An Initial Feasibility Assessment

    Microsoft Academic Search

    Richard Strayer; Jay Garland; Captain Janine

    2008-01-01

    A preliminary assessment was made of the potential for biological production of methane from solid waste generated during an early planetary base mission to the moon. This analysis includes: 1) estimation of the amount of biodegradable solid waste generated, 2) background on the potential biodegradability of plastics given their significance in solid wastes, and 3) calculation of potential methane production

  8. When do tissues and cells become products? – Regulatory oversight of emerging biological therapies

    Microsoft Academic Search

    Albert Farrugia

    2006-01-01

    Although therapeutics derived from biological sources have been subjected to regulatory oversight for some time, the products used in transplantation procedures have historically been exempt from this oversight. These products have been viewed as being part of medical practice rather than as the result of mainstream pharmaceutical manufacture. Furthermore, their unique source makes them difficult to assess in traditional regulatory

  9. Risk in vaccine research and development quantified.

    PubMed

    Pronker, Esther S; Weenen, Tamar C; Commandeur, Harry; Claassen, Eric H J H M; Osterhaus, Albertus D M E

    2013-01-01

    To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates) have been published for new chemical entities (NCE), little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines. PMID:23526951

  10. Risk in Vaccine Research and Development Quantified

    PubMed Central

    Pronker, Esther S.; Weenen, Tamar C.; Commandeur, Harry; Claassen, Eric H. J. H. M.; Osterhaus, Albertus D. M. E.

    2013-01-01

    To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates) have been published for new chemical entities (NCE), little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines. PMID:23526951

  11. The economics of biological methods of hydrogen production

    E-print Network

    Resnick, Richard J. (Richard Jay), 1971-

    2004-01-01

    The costs to produce and utilize hydrogen are extremely high per unit of energy when compared to fossil fuel energy sources such as natural gas or gasoline. The cheapest hydrogen production approaches today are also the ...

  12. Maximum entropy production principle in physics, chemistry and biology

    Microsoft Academic Search

    L. M. Martyushev; V. D. Seleznev

    2006-01-01

    The tendency of the entropy to a maximum as an isolated system is relaxed to the equilibrium (the second law of thermodynamics) has been known since the mid-19th century. However, independent theoretical and applied studies, which suggested the maximization of the entropy production during nonequilibrium processes (the so-called maximum entropy production principle, MEPP), appeared in the 20th century. Publications on

  13. Packet Vaccine: Black-box Exploit Detection and Signature Generation

    E-print Network

    Wang, XiaoFeng

    jump address be- haves like a vaccine: it will likely cause an exception in a vulnerable programPacket Vaccine: Black-box Exploit Detection and Signature Generation XiaoFeng Wang1 , Zhuowei Li1. ABSTRACT In biology, a vaccine is a weakened strain of a virus or bac- terium that is intentionally

  14. Vaccine-Enhanced Artificial Immune System for Multimodal Function Optimization

    Microsoft Academic Search

    Kumlachew M. Woldemariam; Gary G. Yen

    2010-01-01

    This paper emulates a biological notion in vaccines to promote exploration in the search space for solving multimodal function optimization problems using artificial immune systems (AISs). In this method, we first divide the decision space into equal subspaces. The vaccine is then randomly extracted from each subspace. A few of these vaccines, in the form of weakened antigens, are then

  15. Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology

    PubMed Central

    Jarboe, Laura R.; Zhang, Xueli; Wang, Xuan; Moore, Jonathan C.; Shanmugam, K. T.; Ingram, Lonnie O.

    2010-01-01

    Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors. PMID:20414363

  16. Vaccine legislation.

    PubMed

    1999-07-23

    Rep. Nancy Pelosi (D-Calif.) has introduced the Lifesaving Vaccine Technology Act of 1999, designed to provide biotechnology and pharmaceutical companies with a 30 percent tax credit for costs associated with vaccine development. Sen. John Kerry (D-Mass.) is drafting similar legislation in the Senate. The tax credits would apply to vaccines for HIV, tuberculosis and malaria, which together kill more than 7 million people worldwide each year. The bill has not made it out of the House Ways and Means Committee; Pelosi hopes to attach the bill to one of several tax-cutting measures scheduled for a vote before the summer congressional recess. PMID:11366597

  17. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...the biologics under review and the full report... Biological Products Review Information I. Label...medical and scientific literature. B. Combinations...marketing, or published literature. If the submission...Deliberations of an advisory review panel. An...

  18. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...the biologics under review and the full report... Biological Products Review Information I. Label...medical and scientific literature. B. Combinations...marketing, or published literature. If the submission...Deliberations of an advisory review panel. An...

  19. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...the biologics under review and the full report... Biological Products Review Information I. Label...medical and scientific literature. B. Combinations...marketing, or published literature. If the submission...Deliberations of an advisory review panel. An...

  20. Biopharming, bananas and bureaucracy: the banana vaccine as a case study for products that straddle the definitional food/drug divide.

    PubMed

    Birdsall, Margaux

    2011-01-01

    This paper examines the definition of the terms "food" and "drug" as used in the Food, Drug and Cosmetic Act through the lens of biopharmed products. The paper uses the so-called "banana vaccine" as a case study to highlight the problems that occur when attempting to regulate a product that could be safely used as a food or as a drug. Specifically, the examination of this model illustrates the problems in the current definitional scheme. The paper considers how a product that straddles the definitional line between food and drug could be regulated and proposes a reformation to how the definitions are applied to products to better suit new technology in food and drugs. PMID:24505843

  1. Drugs@FDA: FDA Approved Drug Products

    MedlinePLUS

    ... A to Z Index Follow FDA En Español Enter Search terms Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products ... Search by Drug Name, Active Ingredient, or Application Number Enter at least three characters: Advanced Search Browse by ...

  2. Current good manufacturing practice in plant automation of biological production processes

    Microsoft Academic Search

    R. C. Dorresteijn; G. Wieten; P. T. E. van Santen; M. C. Philippi; C. D. de Gooijer; J. Tramper; E. C. Beuvery

    1997-01-01

    The production of biologicals is subject to strict governmental regulations. These are drawn up in current good manufacturing practices (cGMP), a.o. by the U.S. Food and Drug Administration. To implement cGMP in a production facility, plant automation becomes an essential tool. For this purpose Manufacturing Execution Systems (MES) have been developed that control all operations inside a production facility. The

  3. Feasibility Study of GlaxoSmithKline Biologicals' GSK2202083A Vaccine in Healthy Infants at 3, 5 and 11 Months of Age.

    ClinicalTrials.gov

    2012-11-16

    Haemophilus Influenzae Type b; Poliomyelitis; Hepatitis B; Serogroup C Meningococcal Diseases; Diphtheria; Pertussis; Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b-Neisseria Meningitidis Vaccines; Tetanus

  4. Increasing algal photosynthetic productivity by integrating ecophysiology with systems biology.

    PubMed

    Peers, Graham

    2014-11-01

    Oxygenic photosynthesis is the process by which plants, algae, and cyanobacteria convert sunlight and CO2 into chemical energy and biomass. Previously published estimates suggest that algal photosynthesis is, at best, able to convert approximately 5-7% of incident light energy to biomass and there is opportunity for improvement. Recent analyses of in situ photophysiology in mass cultures of algae and cyanobacteria show that cultivation methods can have detrimental effects on a cell's photophysiology - reinforcing the need to understand the complex responses of cell biology to a highly variable environment. A systems-based approach to understanding the stresses and efficiencies associated with light-energy harvesting, CO2 fixation, and carbon partitioning will be necessary to make major headway toward improving photosynthetic yields. PMID:25306192

  5. Typhoid Vaccine

    MedlinePLUS

    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, ... a typhoid carrier. • Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot) • One dose ...

  6. Oral vaccines

    PubMed Central

    Zhu, Qing; Berzofsky, Jay A.

    2013-01-01

    Oral vaccines are safe and easy to administer and convenient for all ages. They have been successfully developed to protect from many infectious diseases acquired through oral transmission. We recently found in animal models that formulation of oral vaccines in a nanoparticle-releasing microparticle delivery system is a viable approach for selectively inducing large intestinal protective immunity against infections at rectal and genital mucosae. These large-intestine targeted oral vaccines are a potential substitute for the intracolorectal immunization, which has been found to be effective against rectogenital infections but is not feasible for mass vaccination. Moreover, the newly developed delivery system can be modified to selectively target either the small or large intestine for immunization and accordingly revealed a regionalized immune system in the gut. Future applications and research endeavors suggested by the findings are discussed. PMID:23493163

  7. Pertussis Vaccine

    Cancer.gov

    The National Institute of Child Health and Human Development (NICHD) is seeking statements of capability or interest from parties interested in collaborative research to further co-develop vaccines against pertussis.

  8. HPV Vaccine

    MedlinePLUS

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español ... Body Image HPV Vaccine KidsHealth > Teens > Sexual Health > STDs & ...

  9. Meningococcal vaccines.

    PubMed

    Bethell, Delia; Pollard, Andrew J

    2002-06-01

    The successful introduction of a protein-polysaccharide conjugate vaccine against serogroup C meningococci into the UK infant immunization schedule, in combination with a catch-up campaign for individuals less than 18 years of age, has seen virtually all group C disease eliminated in childhood. From being a devastating disease with a very high mortality, the possibility of eradicating invasive meningococcal disease now seems eminently feasible. Since similar technology is likely to facilitate prevention of disease caused be serogroup A, Y and W135 meningococci, the major hurdle in achieving the goal of eradication is development of a safe and immunogenic vaccine against serogroup B infections. Outer membrane vesicle vaccines remain in development and further trials are anticipated. Through the recent availability of the meningococcal genome sequence, many new vaccine candidates are being identified and there is increasing optimism that a solution to the problem can be found. PMID:12908514

  10. Natural infection of cattle with an atypical 'HoBi'-like pestivirus--implications for BVD control and for the safety of biological products.

    PubMed

    Ståhl, Karl; Kampa, Jaruwan; Alenius, Stefan; Persson Wadman, Annie; Baule, Claudia; Aiumlamai, Suneerat; Belák, Sándor

    2007-01-01

    During a study on Bovine Viral Diarrhoea (BVD) epidemiology in Thailand, a pestivirus was detected in serum from a calf. Comparative nucleotide sequence analysis showed that this virus was closely related to a recently described atypical pestivirus (D32/00_'HoBi') that was first isolated from a batch of foetal calf serum collected in Brazil. The results from virus neutralisation tests performed on sera collected from cattle in the herd of the infected calf, showed that these cattle had markedly higher antibody titres against the atypical pestivirus 'HoBi' than against Bovine Viral Diarrhoea Virus types 1 and 2, or Border Disease Virus. The results also supported, consequently, the results from the molecular analysis, and demonstrated that a 'HoBi'-like pestivirus had been introduced to, and was now circulating in the herd. This study is the first to report a natural infection in cattle with a virus related to this atypical pestivirus, and it suggests that this group of pestiviruses may already be spread in cattle populations. The findings have implications for BVD control and for the biosafety of vaccines and other biological products produced with foetal calf serum. Consequently, these atypical pestiviruses should be included in serological assays, and any diagnostic assay aimed at detection of pestiviruses in biological products or animals should be tested for its ability to detect them. PMID:17506974

  11. Physicochemical and functional characterization of vaccine antigens and adjuvants.

    PubMed

    Dey, Antu K; Malyala, Padma; Singh, Manmohan

    2014-05-01

    As novel vaccine antigens and adjuvants are being tested in humans, understanding of critical quality attributes essential for eliciting optimal vaccine response and vaccine antigen-adjuvant interactions is pivotal for vaccine safety and eliciting 'protective' immune responses. Therefore, the efforts to better characterize and evaluate vaccine antigen and antigen-adjuvant drug products need to begin very early during the discovery and development phase. In this review, we discuss the importance of characterization of physicochemical and functional properties in vaccine antigen, adjuvant and the final antigen-adjuvant drug product and emphasize the greater need for more extensive understanding of vaccine antigen-adjuvant interactions. We highlight the key parameters and quality attributes that are critical to measure during preclinical and clinical testing of the vaccine and discuss in some detail the technologies, and their limitations, used in analyzing the key physicochemical and functional attributes of vaccine antigen and antigen-adjuvant drug product. PMID:24702271

  12. DISINFECTION BY-PRODUCT CONTROL THROUGH BIOLOGICAL FILTRATION

    EPA Science Inventory

    Disinfection by-product (DBP) control through biofiltration is defined as the removal of DBP precursor mateterial (PM) by bacteria attached to the filte nedia. The PM consists of dissolved organic matter (DOM) and is utilized by the filter bacteria as a substrate for cell mainten...

  13. Perspectives and advances of biological H 2 production in microorganisms

    Microsoft Academic Search

    Jens Rupprecht; Ben Hankamer; Jan H. Mussgnug; Gennady Ananyev; Charles Dismukes; Olaf Kruse

    2006-01-01

    The rapid development of clean fuels for the future is a critically important global challenge for two main reasons. First, new fuels are needed to supplement and ultimately replace depleting oil reserves. Second, fuels capable of zero CO2 emissions are needed to slow the impact of global warming. This review summarizes the development of solar powered bio-H2 production processes based

  14. Phytosterol Oxidation Products: Their Formation, Occurrence, and Biological Effects

    Microsoft Academic Search

    Eileen Ryan; Florence O. McCarthy; Anita R. Maguire; Nora M. OBrien

    2009-01-01

    Phytosterols or plant sterols are integral natural components of plant cell membranes that are abundant in vegetable oils, nuts, seeds, and grains; as well as added components in various functional foods. Due to their chemical structure, phytosterols are susceptible to oxidation under certain conditions giving rise to a family of compounds known as phytosterol oxidation products (POPs). The following review

  15. Bacterial and other biological systems for polyester production

    Microsoft Academic Search

    Alexander Steinbüchel; Bernd Füchtenbusch

    1998-01-01

    Poly(3-hydroxybutyric acid) and other structurally related aliphatic polyesters from bacteria, referred to as polyhydroxyalkanoic acids, form biodegradable thermoplastics and elastomers that are currently in use, or being considered for use, in industry, medicine, pharmacy and agriculture. At present, they are produced by microbial fermentations; in the future, production will also be possible by in vitro methods or by agriculture using

  16. Bovine mammary stem cells: Cell biology meets production agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  17. Veterinary autogenous vaccines.

    PubMed

    Hera, A; Bures, J

    2004-01-01

    Autogenous vaccines remain a regulatory issue. They are demanded by practising veterinarians and by animal owners and they are quite widely used, mainly in Central European Countries, the Czech Republic, Hungary and Slovak Republic having probably the longest tradition with these products in Central Europe. The scope given in Article 3, Para. 2 (and/or Article 4 for some countries) of Directive 2001/82/EC applies to these products in the Acceding Countries. As these products are exempt from the harmonised regulation at the EU level, they are regulated by individual countries, the regulation varying from practically no regulatory measures in certain countries to a quite complex and demanding regulation in the other countries. Both risks and benefits are related to these products and they shall be taken into account when regulatory measures are considered. The major risks related to veterinary autogenous vaccines relate to possibility of transmission of TSE agents or other viral, bacterial and/or fungal contaminants. As appropriate and well balanced regulation of these products is deemed necessary, considering the risks related to these products, and based on the fact that national regulatory measures could be considered as a trade barrier under certain circumstances, harmonisation of the key issues or legal admission of the nationally based regulatory measures, including movement of these products from the other Member States, shall be laid down in the EU legislation. The veterinary autogenous vaccines complying with basic quality and safety requirements are thus a very useful tool in the animal health and welfare management but their use should be restricted to situations where there is no authorised veterinary medicinal product available and veterinary autogenous vaccines must not be allowed to replace good farming or veterinary practices. PMID:15597612

  18. Your baby's first vaccines

    MedlinePLUS

    ... to the antibiotics neomycin, streptomycin or polymyxin B. Hepatitis B vaccine , if your child has a severe allergy to ... half of vaccinations, depending on the vaccine. Polio, Hepatitis B and Hib vaccines have been associated only with these kinds of ...

  19. Your Baby's First Vaccines

    MedlinePLUS

    ... to the antibiotics neomycin, streptomycin or polymyxin B. Hepatitis B vaccine , if your child has a severe allergy to ... half of vaccinations, depending on the vaccine. Polio, Hepatitis B and Hib Vaccines have been associated only with these kinds of ...

  20. Recent progress in synthetic biology for microbial production of C3–C10 alcohols

    PubMed Central

    Lamsen, Edna N.; Atsumi, Shota

    2012-01-01

    The growing need to address current energy and environmental problems has sparked an interest in developing improved biological methods to produce liquid fuels from renewable sources. While microbial ethanol production is well established, higher-chain alcohols possess chemical properties that are more similar to gasoline. Unfortunately, these alcohols (except 1-butanol) are not produced efficiently in natural microorganisms, and thus economical production in industrial volumes remains a challenge. Synthetic biology, however, offers additional tools to engineer synthetic pathways in user-friendly hosts to help increase titers and productivity of these advanced biofuels. This review concentrates on recent developments in synthetic biology to produce higher-chain alcohols as viable renewable replacements for traditional fuel. PMID:22701113

  1. Therapeutic Vaccines for Gastrointestinal Cancers

    PubMed Central

    Rahma, Osama E.

    2011-01-01

    Despite progress in the management of gastrointestinal malignancies, these diseases remain devastating maladies. Conventional treatment with chemotherapy and radiation is still only partially effective and highly toxic. In the era of increasing knowledge of the molecular biology of tumors and the interaction between the tumor and immune system, the development of targeted agents, including cancer vaccines, has emerged as a promising modality. In this paper, we discuss the principals of vaccine development, and we review most of the published trials on gastrointestinal cancer vaccines that have been conducted over the last decade. Many antigens and various treatment approaches have already been tested in colon, pancreatic, and other cancers. Some of these approaches have already shown some clinical benefit. In this paper, we discuss these different strategies and some of the future directions for targeting gastrointestinal malignancies with vaccines. PMID:22298988

  2. Development of a new candidate H5N1 avian influenza virus for pre-pandemic vaccination production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND. Highly pathogenic H5N1 avian influenza viruses currently circulating in birds have caused hundreds of human infections, and pose a significant pandemic threat. Vaccines are a major component of the public health sector preparedness for this likely event. The rapid evolution of H5N1 vi...

  3. Biological Hydrogen Production Using Chloroform-treated Methanogenic Granules

    NASA Astrophysics Data System (ADS)

    Hu, Bo; Chen, Shulin

    In fermentative hydrogen production, the low-hydrogen-producing bacteria retention rate limits the suspended growth reactor productivity because of the long hydraulic retention time (HRT) required to maintain adequate bacteria population. Traditional bacteria immobilization methods such as calcium alginate entrapment have many application limitations in hydrogen fermentation, including limited duration time, bacteria leakage, cost, and so on. The use of chloroform-treated anaerobic granular sludge as immobilized hydrogen-producing bacteria in an immobilized hydrogen culture may be able to overcome the limitations of traditional immobilization methods. This paper reports the findings on the performance of fed-batch cultures and continuous cultures inoculated with chloroform-treated granules. The chloroform-treated granules were able to be reused over four fed-batch cultures, with pH adjustment. The upflow reactor packed with chloroform-treated granules was studied, and the HRT of the upflow reactor was found to be as low as 4 h without any decrease in hydrogen production yield. Initial pH and glucose concentration of the culture medium significantly influenced the performance of the reactor. The optimum initial pH of the culture medium was neutral, and the optimum glucose concentration of the culture medium was below 20 g chemical oxygen demand/L at HRT 4 h. This study also investigated the possibility of integrating immobilized hydrogen fermentation using chloroform-treated granules with immobilized methane production using untreated granular sludge. The results showed that the integrated batch cultures produced 1.01 mol hydrogen and 2 mol methane per mol glucose. Treating the methanogenic granules with chloroform and then using the treated granules as immobilized hydrogen-producing sludge demonstrated advantages over other immobilization methods because the treated granules provide hydrogen-producing bacteria with a protective niche, a long duration of an active culture, and excellent settling velocity. This integrated two-stage design for immobilized hydrogen fermentation and methane production offers a promising approach for modifying current anaerobic wastewater treatment processes to harvest hydrogen from the existing systems.

  4. BIOLOGICALLY ACTIVE NATURAL PRODUCTS OF THE GENUS CALLICARPA?

    PubMed Central

    JONES, WILLIAM P.; KINGHORN, A. DOUGLAS

    2009-01-01

    About 20 species from Callicarpa have reported ethnobotanical and ethnomedical uses, and several members of this genus are well known in the traditional medical systems of China and South Asia. Ethnomedical reports indicate their use in the treatment of hepatitis, rheumatism, fever, headache, indigestion, and other ailments. Several species of Callicarpa have been reported to be used against cancer (e.g., Callicarpa americana root to treat skin cancer and Callicarpa rubella bark to treat tumors of the large intestine). Extracts from about 14 species in this genus have been evaluated for biological activity, including antibacterial, antifungal, anti-insect growth, cytotoxic, and phytotoxic activities. In addition to amino acids, benzenoids, simple carbohydrates, and lipids, numerous diterpenes, flavonoids, phenylpropanoids, phytosterols, sesquiterpenes, and triterpenes have been detected in or isolated from the genus Callicarpa. The essential oils of Callicarpa americana have recently been reported to have antialgal and phytotoxic activities, and several isolates from this species (and C. japonica) were identified as contributing to the mosquito bite-deterrent activity that was first indicated by folkloric usage. Recent bioassay-guided investigations of C. americana extracts have resulted in the isolation of several active compounds, mainly of the clerodane diterpene structural type. PMID:19830264

  5. 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

  6. Early history of regulatory requirements for poultry biologics in the United States.

    PubMed

    Espeseth, David A; Lasher, Hiram

    2010-12-01

    Congress passed the Virus-Serum-Toxin Act in 1913, giving the U.S. Department of Agriculture (USDA) authority to prevent the importation or interstate shipment of worthless, contaminated, dangerous, or harmful veterinary biological products. The passage of this act marked the beginning of regulatory requirements for veterinary biological products in the United States. In 1913, only a few biologics establishments produced products for the poultry industry. The first license issued by the USDA for a poultry product was in 1918 to the University of California, Berkeley, for fowlpox vaccine. The list of biological products for poultry grew slowly in the 1920s. However, this began to change with the licensing of laryngotracheitis vaccine in 1933; pigeonpox vaccine in 1939; several Newcastle disease vaccines (inactivated in 1946, Roakin strain in 1948, B1 strain in 1950, and La Sota strain in 1952); and the first bronchitis vaccine in 1953. With the development of these and other new products, the biologics industry began to move its emphasis on hog cholera serum and virus to one based on the production of numerous new vaccines and bacterial products. The USDA's approach to the regulation of biologics in the early 1950s was still geared to the production of hog cholera products; however, as a result of the intervention of a group of dedicated poultry scientists, who were concerned about the poor performance of Newcastle disease vaccines, this soon changed. This presentation describes the initiation and development of modern standards for poultry biologics that occurred as a result of this intervention. The development and improvement of standards and regulatory requirements to address mycoplasma, leukosis, and other extraneous virus contaminations in chicken embryo origin products are reviewed. The licensing of products to meet new and emerging disease problems in the poultry industry and the close interaction among research scientists, poultry industry, biologics manufacturers, and government regulatory officials that has been needed to ensure the availability of products that meet appropriate standards of purity, safety, potency, and efficacy are also addressed. PMID:21313831

  7. Overview of vaccines and vaccination

    Microsoft Academic Search

    Gordon Ada

    2005-01-01

    Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral\\u000a and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. This\\u000a article describes the nature of the vaccines, from live attenuated agents to subunits, their efficacy and safety, and the\\u000a kind of the

  8. Smallpox vaccine: contraindications, administration, and adverse reactions.

    PubMed

    Maurer, Douglas M; Harrington, Brian; Lane, J Michael

    2003-09-01

    Since the terrorist attacks of September 11, 2001, and the anthrax exposures in the following weeks, concern that smallpox could be used as a biologic weapon has increased. Public health departments and the U.S. military have begun the process of vaccinating soldiers and civilian first-responders. Smallpox vaccination carries some serious risks: approximately one in 1 million primary vaccinees and one in 4 million revaccinees will die from adverse vaccine reactions. The most serious side effects of smallpox vaccine include progressive vaccinia, postvaccinial central nervous system disease, and eczema vaccinatum. Some of these reactions can be treated with vaccinia immune globulin or cidofovir. Proper patient screening and site care are essential. Family physicians must learn to screen potential vaccinees for contraindications (e.g., immunodeficiency, immunosuppression, certain skin and eye diseases, pregnancy, lactation, allergy to the vaccine or its components, moderate or severe intercurrent illness) and to treat vaccine-associated adverse reactions. PMID:13678138

  9. Formulation and delivery of dermal DNA vaccines

    Microsoft Academic Search

    J. H. van den Berg

    2009-01-01

    DNA vaccination is an appealing strategy of active vaccination, leading to the intracellular production of the encoding antigen which results in an efficient activation of an antigen specific immune response. Intradermal DNA tattooing was recently developed as a simple and robust method to induce antigen expression and T cell responses. This thesis focused on the pharmaceutical production and formulation, and

  10. New opportunities by synthetic biology for biopharmaceutical production in Pichia pastoris

    PubMed Central

    Vogl, Thomas; Hartner, Franz S; Glieder, Anton

    2013-01-01

    Biopharmaceuticals are an integral part of modern medicine and pharmacy. Both, the development and the biotechnological production of biopharmaceuticals are highly cost-intensive and require suitable expression systems. In this review we discuss established and emerging tools for reengineering the methylotrophic yeast Pichia pastoris for biopharmaceutical production. Recent advancements of this industrial expression system through synthetic biology include synthetic promoters to avoid methanol induction and to fine-tune protein production. New platform strains and molecular cloning tools as well as in vivo glycoengineering to produce humanized glycoforms have made P. pastoris an important host for biopharmaceutical production. PMID:23522654

  11. New approaches to estimation of peat deposits for production of biologically active compounds

    NASA Astrophysics Data System (ADS)

    Stepchenko, L. M.; Yurchenko, V. I.; Krasnik, V. G.; Syedykh, N. J.

    2009-04-01

    It is known, that biologically active preparations from peat increase animals productivity as well as resistance against stress-factors and have adaptogeneous, antioxidant, immunomodulative properties. Optymal choice of peat deposits for the production of biologically active preparations supposes the detailed comparative analysis of peat properties from different deposits. For this the cadastre of peat of Ukraine is developed in the humic substances laboratory named after prof. Khristeva L.A. (Dnipropetrovsk Agrarian University, Ukraine). It based on the research of its physical and chemical properties, toxicity and biological activity, and called Biocadastre. The Biocadastre is based on the set of parameters, including the descriptions of physical and chemical properties (active acidity, degree of decomposition, botanical composition etc.), toxicity estimation (by parabyotyc, infusorial, inhibitor and other tests), biological activity indexes (growth-promoting, antioxidative, adaptogeneous, immunomodulative antistress and other actions). The blocks of Biocadastre indexes are differentiated, taking into account their use for creation the preparations for vegetable, animals and microorganisms. The Biocadastre will allow to choose the peat deposits, most suitable for the production of different biologically active preparations, both wide directed and narrow spectrum of action, depending on application fields (medicine, agriculture, veterinary medicine, microbiological industry, balneology, cosmetology).

  12. Kunjin virus replicons: an RNA-based, non-cytopathic viral vector system for protein production, vaccine and gene therapy applications.

    PubMed

    Pijlman, Gorben P; Suhrbier, Andreas; Khromykh, Alexander A

    2006-02-01

    The application of viral vectors for gene expression and delivery is rapidly evolving, with several entering clinical trials. However, a number of issues, including safety, gene expression levels, cell selectivity and antivector immunity, are driving the search for new vector systems. A number of replicon-based vectors derived from positive-strand RNA viruses have recently been developed, and this paper reviews the current knowledge on the first flavivirus replicon system, which is based on the Australian flavivirus Kunjin (KUN). Like most replicon systems, KUN replicons can be delivered as DNA, RNA or virus-like particles, they replicate their RNA in the cytoplasm and direct prolonged high-level gene expression. However, unlike most alphavirus replicon systems, KUN replicons are non-cytopathic, with transfected cells able to divide, allowing the establishment of cell lines stably expressing replicon RNA and heterologous genes. As vaccine vectors KUN replicons can induce potent, long-lived, protective, immunogen-specific CD8+ T cell immunity, a feature potentially related to extended production of antigen and double-stranded RNA-induced 'danger signals'. The identification of KUN replicon mutants that induce increased levels of IFN-alpha/beta has also spawned investigation of KUN replicons for use in cancer gene therapy. The unique characteristics of KUN replicons may thus make them suitable for specific protein production, vaccine and gene therapy applications. PMID:16436039

  13. Synthetic biology: tools to design microbes for the production of chemicals and fuels.

    PubMed

    Seo, Sang Woo; Yang, Jina; Min, Byung Eun; Jang, Sungho; Lim, Jae Hyung; Lim, Hyun Gyu; Kim, Seong Cheol; Kim, Se Yeon; Jeong, Jun Hong; Jung, Gyoo Yeol

    2013-11-01

    The engineering of biological systems to achieve specific purposes requires design tools that function in a predictable and quantitative manner. Recent advances in the field of synthetic biology, particularly in the programmable control of gene expression at multiple levels of regulation, have increased our ability to efficiently design and optimize biological systems to perform designed tasks. Furthermore, implementation of these designs in biological systems highlights the potential of using these tools to build microbial cell factories for the production of chemicals and fuels. In this paper, we review current developments in the design of tools for controlling gene expression at transcriptional, post-transcriptional and post-translational levels, and consider potential applications of these tools. PMID:23578899

  14. Combination vaccines in the South African setting.

    PubMed

    Visser, Adele; Hoosen, Anwar

    2012-09-01

    The number of vaccines available and included as part of the national immunization schedules, has increased significantly over the past few decades. This impacts on patient/parent compliance and creates a challenge for health care providers for implementation of schedules necessitating training and infrastructure improvements. Use of combination rather than component vaccines offers advantages for compliance by single dose administration of various antigens, reducing stock costing as well as reducing cost of additional health care visits. Combination vaccines are often significantly more expensive than individual constituent vaccines. Concerns regarding an increased incidence of adverse events with use of combination vaccines have not been confirmed and rates may seem high as the adverse events seem to mimic the sum total of adverse event rates for each individual antigen used but may in fact be lower. Manufacturers typically advise against interchanging use of vaccine products. Despite this, health authorities advocate use of an alternative vaccine where the original vaccine in not available, to ensure continuity of vaccination. A notable exception is the acellular pertussis vaccine. Partly, because no serological correlates of immunity exist, but also a general lack of convincing follow up studies has prompted the recommendation for manufacturer fidelity for at least the first 3 vaccine doses. According to the South African Medicines Formulary, a variety of vaccines are available in South Africa. Although a large number are available in the private sector, the only true combination vaccine included in the current state EPI, modified in 2009, is the DTaP-IPV/Hib vaccine (Diphtheria, Tetanus, acellular Pertussis, inactivated Poliomyelitis virus and Haemophilus influenzae type b). There are many reasons justifying the use of combination vaccines rather that the individual constituent formulations. Implementation of use in the South African setting at this point is still limited, but may offer an exciting avenue of expanding the antigen repertoire without impacting on side-effects, efficacy or complexity of scheduling. PMID:22939020

  15. 70 FR 43694 - Proposed Vaccine Information Materials for Hepatitis A and Influenza Vaccines; Interim Vaccine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2005-07-28

    ...Proposed Vaccine Information Materials for Hepatitis A and Influenza Vaccines; Interim Vaccine...new vaccine information materials for hepatitis A and trivalent influenza vaccines...Vaccine Injury Compensation Program: hepatitis B, haemophilus influenzae type b...

  16. Current studies on biological tagatose production using l-arabinose isomerase: a review and future perspective

    Microsoft Academic Search

    Pil Kim

    2004-01-01

    d-Tagatose is a hexoketose monosaccharide sweetener, which is an isomer of d-galactose and is rarely found in nature. Recently, there has been industrial interest in d-tagatose as a low-calorie sugar-substituting sweetener. This article describes the properties and metabolism of tagatose as well as its commercial importance. The comparison between the biological tagatose production and the chemical production was reviewed based

  17. Biological production of acetaldehyde from ethanol using non-growing Pichia pastoris whole cells

    SciTech Connect

    Chiang, Heien-Kun; Foutch, G.L. [Oklahoma State Univ., Stillwater, OK (United States); Fish, W.W. [Phillips Petroleum Co., Bartlesville, OK (United States)

    1991-12-31

    Acetaldehyde has been produced biologically using whole-cell Pichia Pass in a semibatch fermentor. Ethanol and air were fed continuously, and the product, acetaldehyde, was removed by the air stream. Operation of the reactor exceeded 100 h, maintaining high alcohol oxidase activity. Low cell-mass concentration (9.9 g/L) minimized product inhibition. Ethanol concentration in the broth, oxygen concentration in the air, and pH were evaluated for their effects on the fermentation process.

  18. FDA: Center for Biologics Evaluation and Research

    NSDL National Science Digital Library

    The mission of the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) is "to protect and enhance the public health through the regulation of biological and related products including blood, vaccines, allergenics, tissues, and cellular and gene therapies." Their mission is an important one, and consumers and scientists will want to bookmark this page and return to it on a regular basis. On this page, visitors can sign up for their RSS feed and read through some key resources. Users can also browse resources on biologics depending on their needs: consumer, healthcare and industry level information is provided.

  19. A field survey of chemicals and biological products used in shrimp farming

    Microsoft Academic Search

    S Gräslund; K Holmström; A Wahlström

    2003-01-01

    This study documented the use of chemicals and biological products in marine and brackish water shrimp farming in Thailand, the world’s top producer of farmed shrimp. Interviews were conducted with 76 shrimp farmers in three major shrimp producing regions, the eastern Gulf coast, the southern Gulf coast and the Andaman coast area. Farmers in the study used on average 13

  20. Biological amendment, fertilizer rate, and irrigation frequency for bell pepper transplant production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Use of biological amendments in vegetable transplant production systems may affect development of plants. In an initial experiment a mix of Rhizobium sp. bacteria, a mix of vesicular-arbuscular mycorrhizal fungi, or a combination of the bacteria and fungi were added to an organically certified pott...

  1. The Analysis of Cyanide and its Breakdown Products in Biological Samples

    Microsoft Academic Search

    Brian A. Logue; Diane M. Hinkens; Steven I. Baskin; Gary A. Rockwood

    2010-01-01

    Cyanide is a toxic chemical that may be introduced into living organisms as a result of natural processes and\\/or anthropogenic uses (legal or illicit). Exposure to cyanide can be verified by analysis of cyanide or one of its breakdown products from biological samples. This verification may be important for medical, law-enforcement, military, forensic, research, or veterinary purposes. This review will

  2. 77 FR 30887 - Amendments to Sterility Test Requirements for Biological Products; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration...0910-AG16 Amendments to Sterility Test Requirements for Biological...appropriate and state-of-the-art test methods for assuring the safety...Products, in Sec. 680.3 Tests, paragraph (c), in...

  3. ORFeome Cloning and Systems Biology: Standardized Mass Production of the Parts

    E-print Network

    ORFeome Cloning and Systems Biology: Standardized Mass Production of the Parts From the Parts, as predicted from genome and transcriptome sequences. Here we discuss the use of a recombinational cloning, the "parts-lists," are available for several model organisms and for human. With such parts-lists in hand

  4. The effect of soluble microbial products on membrane fouling in a fixed carrier biological system

    Microsoft Academic Search

    Kok-Kwang Ng; Cheng-Fang Lin; Shaik Khaja Lateef; Sri Chandana Panchangam; Pui-Kwan Andy Hong; Ping-Yi Yang

    2010-01-01

    The fixed carrier biological system (FCBS) has been developed for treatment of wastewater with an intent to achieve high simultaneous removal of carbon and nitrogen in a single through-put process. It is believed that a longer sludge retention time (SRT), high dissolved oxygen (DO), low suspended solids and good contact with the bio-balls in an FCBS possibly enable less production

  5. Rapid differentiation of vaccine strains and field isolates of infectious laryngotracheitis virus by restriction fragment length polymorphism of PCR products

    Microsoft Academic Search

    Poa-Chun Chang; Yuan-Ling Lee; Jui-Hung Shien; Happy K. Shieh

    1997-01-01

    A procedure was developed for differentiation of vaccine strains and field isolates of infectious laryngotracheitis virus (ILTV) by restriction fragment length polymorphism (RFLP) of DNA fragments amplified from the genome of ILTV by polymerase chain reaction (PCR). RFLP patterns of viral thymidine kinase (TK) gene, glycoprotein C (gC) gene, glycoprotein X (gX) gene and ICP4 gene amplified from different ILT

  6. Removing residual DNA from Vero-cell culture-derived human rabies vaccine by using nuclease.

    PubMed

    Li, Si-Ming; Bai, Fu-Liang; Xu, Wen-Juan; Yang, Yong-Bi; An, Ying; Li, Tian-He; Yu, Yin-Hang; Li, De-Shan; Wang, Wen-Fei

    2014-09-01

    The clearance of host cell DNA is a critical indicator for Vero-cell culture-derived rabies vaccine. In this study, we evaluated the clearance of DNA in Vero-cell culture-derived rabies vaccine by purification process utilizing ultrafiltration, nuclease digestion, and gel filtration chromatography. The results showed that the bioprocess of using nuclease decreased residual DNA. Dot-blot hybridization analysis showed that the residual host cell DNA was <100 pg/ml in the final product. The residual nuclease in rabies vaccine was less than 0.1 ng/ml protein. The residual nuclease could not paly the biologically active role of digestion of DNA. Experiments of stability showed that the freeze-drying rabies virus vaccine was stable and titers were >5.0 IU/ml. Immunogenicity test and protection experiments indicated mice were greatly induced generation of neutralizing antibodies and invoked protective effects immunized with intraperitoneal injections of the rabies vaccine. These results demonstrated that the residual DNA was removed from virus particles and nuclease was removed by gel filtration chromatography. The date indicated that technology was an efficient method to produce rabies vaccine for human use by using nuclease. PMID:25108516

  7. Type I IFN as a vaccine adjuvant for both systemic and mucosal vaccination against influenza virus

    Microsoft Academic Search

    Laura Bracci; Irene Canini; Massimo Venditti; Massimo Spada; Simona Puzelli; Isabella Donatelli; Filippo Belardelli; Enrico Proietti

    2006-01-01

    Type I IFN is a cytokine family endowed with multiple biological activities. In recent years, type I IFN has been demonstrated to play a crucial role in innate immunity, in dendritic cell maturation\\/differentiation and in the priming of primary antibody responses, especially when administered i.m. with a purified influenza vaccine. Due to the increasing interest in mucosal vaccination especially for

  8. [Special considerations for the regulation of biological medicinal products in individualised medicine. More than stratified medicine].

    PubMed

    Müller-Berghaus, J; Volkers, P; Scherer, J; Cichutek, K

    2013-11-01

    The term individualised medicine, also called personalised medicine, is commonly used as an equivalent to stratified medicine. However, this is erroneous since quite often it is forgotten that especially biological medicinal products have other aspects of individualization that go beyond mere stratification. The principles of stratified medicine have been applied for biological medicinal products for many years. A historical example is diphtheria antitoxin made from horse serum, while current examples are transfusion of red blood cells and the administration of factor VIII in haemophilia A. The stratifying aspects of these medicinal products are given by the following considerations: diphtheria antitoxin is only administered after a diagnosis of diphtheria and not in other forms of tonsillitis, red blood cells should only be transfused once blood group compatibility as been established and factor VIII replacement is only administered in haemophilia A as opposed to other acquired or hereditary disease of the coagulation system. The peculiarities of biological medicinal products, in particular the inherent variability of the drug, are especially important for autologous cellular medicinal products. In addition to the expected variability of the biological source material there is interindividual variability of patients as cell donors, which make definition of specifications and determination of criteria for pharmaceutical quality and potency tests difficult. Therapy with modified autologous cells, a common and important application of advanced therapy medicinal products, is exemplary for the special considerations that must be made when evaluating pharmaceutical quality, mode of action and toxicological properties of the biological medicine. The clinical investigation of advanced therapy medicinal products with the intent of demonstrating safety and efficacy is particularly challenging because of the complexity of therapy, which often involves invasive interventions. The development of biomarkers accelerates the process towards stratified or individualised therapies. Increased requirements for companion diagnostics are a possible consequence. Progress in analytical processes and in biotechnology make a higher degree of individualization likely, possibly to the degree that medicinal products will be individually manufactured for each patient. Current principles of medicinal product testing and market authorization may be applicable only with limitations, because the individual medicinal products are not uniform and are not repeatedly manufactured. The assessment of the process, performed on several different medicinal products manufactured by the same process could potentially serve as a basis for the assessment. For the evaluation of risk for the patient in clinical trials new concepts must be considered, which can be facilitated by interaction of regulatory authorities and developers. PMID:24170083

  9. Vaccination priorities.

    PubMed

    Steffen, Robert; Baños, Ana; deBernardis, Chiara

    2003-02-01

    Selection of immunizations should be based on requirements and on risk of infection. According to the International Health Regulations, many countries require yellow fever vaccination and proof thereof as the International Certificate of vaccination. Additionally selected countries require proof of vaccination against cholera and meningococcal disease. A consultation for travel health advice is always an opportunity to ascertain that routine immunizations have been performed. Recommended immunizations often are more important for traveller's health than the required or routine ones. The most frequent vaccine preventable infection in non-immune travellers to developing countries is hepatitis A with an average incidence rate of 0.3% per month; in high risk backpackers or foreign-aid-volunteers this rate is 2.0%. Many immunizations are recommended for special risk groups only: there is a growing tendency in many countries to immunize all young travellers to developing countries against hepatitis B, as it is uncertain who will voluntarily or involuntarily get exposed. The attack rate of influenza in intercontinental travel is estimated to be 1%. Immunity against poliomyelitis remains essential for travel to Africa and parts of Asia. Many of the 0.2-0.4% who experience an animal bite are at risk of rabies. Typhoid fever is diagnosed with an incidence rate of 0.03% per month among travellers to the Indian subcontinent, North and West Africa (except Tunisia), and Peru, elsewhere this rate is 10-fold lower. Meningococcal disease, Japanese encephalitis, cholera and tuberculosis have been reported in travellers, but these infections are rare in this population. Although no travel health vaccine is cost beneficial, most professionals will offer protection against the frequent risks, while most would find it ridiculous to use all available vaccines in every traveller. It is essentially an arbitrary decision made on the risk level one wishes to recommend protection--but the priorities need to be set correctly. PMID:12615383

  10. Cytomegalovirus Vaccines

    PubMed Central

    McVoy, Michael A.

    2013-01-01

    An effective cytomegalovirus (CMV) vaccine could prevent the majority of birth defects caused by congenital CMV infections. Candidate vaccines in clinical evaluation include live attenuated, protein subunit, DNA, and viral-vectored approaches. Subunit approaches have focused on the CMV proteins pp65 and IE1 as important inducers of cytotoxic T cells and glycoprotein B (gB) as an important inducer of neutralizing antibodies. A vaccine comprised of recombinant gB protein with MF59 adjuvant reduced the incidence of primary infection by 50%. Recent revelations regarding CMV entry pathways into different cell types suggest a possible course for improvement. A 5-subunit pentameric complex is uniquely required for endothelial and epithelial cell entry. Sera from naturally infected subjects contain high-potency neutralizing activities specific for this complex, whereas the gB/MF59 vaccine fails to induce comparable neutralizing activities. A vaccine's ability to induce salivary antibodies that neutralize epithelial cell entry may be especially important for preventing oral transmission as the first cells infected are presumably epithelial cells of the oral mucosa. In addition, recent evidence suggests that antibodies can inhibit postentry CMV spread between endothelial and epithelial cells. Such activities may serve to limit viral replication in tissues or impair dissemination to the placenta and fetus. Thus, inclusion of epitopes derived from the pentameric complex may provide enhanced efficacy by inducing potent neutralizing/spread-inhibiting antibodies that target virus replication in a broad spectrum of cell types. Next-generation vaccine candidates in preclinical development incorporate peptides, subunits, or multisubunit complexes representing parts or all of the pentameric complex. Approaches include peptides, recombinant proteins, DNA, replication-defective viral vectors, genetically disabled CMV, and inactivated CMV virions. The diversity of novel strategies under development engenders optimism that a successful candidate will emerge. PMID:24257427

  11. Research in advance for FMD novel vaccines.

    PubMed

    Zhang, Liang; Zhang, Jie; Chen, Hao-tai; Zhou, Jian-hua; Ma, Li-na; Ding, Yao-zhong; Liu, Yong-sheng

    2011-01-01

    Foot-and-Mouth Disease (FMD), as a major global animal disease, affects millions of animals worldwide and remains the main sanitary barrier to the international and national trade of animals and animal products. Inactivated vaccination is the most effective measure for prevention of FMD at present, but fail to induce long-term protection and content new requires for production of FMD vaccines. As a number of Researchers hope to obtain satisfactory novel vaccines by new bio-technology, novel vaccines have been studied for more than thirty years. Here reviews the latest research progress of new vaccines, summarizes some importance and raises several suggestions for the future of FMD vaccine. PMID:21635788

  12. Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity.

    PubMed

    Barman, Subrata; Franks, John; Turner, Jasmine C; Yoon, Sun-Woo; Webster, Robert G; Webby, Richard J

    2015-06-22

    The recently detected zoonotic H3N2 variant influenza A (H3N2v) viruses have caused 343 documented cases of human infection linked to contact with swine. An effective vaccine is needed for these viruses, which may acquire transmissibility among humans. However, viruses isolated from human cases do not replicate well in embryonated chicken eggs, posing an obstacle to egg-based vaccine production. To address this issue, we sought to identify egg-adaptive mutations in surface proteins that increase the yield of candidate vaccine viruses (CVVs) in eggs while preserving their immunizing effectiveness. After serial passage of a representative H3N2v isolate (A/Indiana/08/2011), we identified several egg-adaptive combinations of HA mutations and assessed the egg-based replication, antigenicity, and immunogenicity of A/Puerto Rico/8/34 (H1N1, PR8)-based 6+2 reverse genetics CVVs carrying these mutations. Here we demonstrate that the respective combined HA substitutions G1861V+N2461K, N1651K+G1861V, T1281N+N1651K+R762G, and T1281N+N1651K+I102M, all identified after egg passage, enhanced the replication of the CVVs in eggs without substantially affecting their antigenicity or immunogenicity. The mutations were stable, and the mutant viruses acquired no additional substitutions during six subsequent egg passages. We found two crucial mutations, G186V, which was previously defined, and N246K, which in combination improved virus yield in eggs without significantly impacting antigenicity or immunogenicity. This combination of egg-adaptive mutations appears to most effectively generate high egg-based yields of influenza A/Indiana/08/2011-like CVVs. PMID:25999284

  13. Human Vaccines & Immunotherapeutics: News

    PubMed Central

    Riedmann, Eva M.

    2013-01-01

    Oncolytic vaccinia virus vaccine: Promising in liver cancer patients FDA panel endorses quadrivalent influenza vaccines Approval for the first meningitis B vaccine Stallergenes seeks FDA approval for sublingual grass-pollen allergy tablet Live-attenuated dengue vaccine promising in Phase 1 GAVI funds HPV vaccines for girls in developing countries First human trials for new superantigen bioterrorism vaccine Hexyon hexavalent pediatric vaccine recommended for approval

  14. killed-virus influenza vaccine Polio vaccine

    E-print Network

    Shyy, Wei

    killed-virus influenza vaccine Polio vaccine FluMist Thomas Francis, Jr. National Institutes of Health live-virus influenza vaccine Hunein Maassab Jonas Salk Type-A virus trivalent cold that Maassab's innovative, trivalent, cold- adapted influenza vaccine, FluMist, which uses live but weakened

  15. Fiber fractions from processing of barley in production and conservation of a biologic control agent.

    PubMed

    Tuomi, T; Heino, M; Nordström, K; Laakso, S

    2001-05-01

    Carriers are frequently used to overcome problems associated with microbial survival in soil after inoculation. Moreover, the use of carriers can prolong the shelf lives and lessen dusting of both biofungicides and biologic fertilizers. This study investigated the suitability of barley-based fiber fractions as growth media and immobilization matrices in the cultivation of a Streptomyces griseoviridis biologic control agent, as well as for the conservation of obtained biomass in dehydrated hydrogel capsules. The second main ingredient in all the examined carrier matrices was alginate. The aim was to find a hydrogel formulation suited for a production process in which all individual steps, including cultivation of the organism; downstream processing; and formulation, storage, and application of the product (i.e., biologic control agent), are carried out in the hydrogel matrix. Of the tested fractions, brewer's spent grain was the best choice, when considering the price vs the nutrient contents as well as the storage time and ease of processing of the crude and the finished products. It seems that cereal fibers can be replenished with cereal fractions less rich in fiber but having a higher content of utilizable nutrients and, hence, better suited for the production of biomass. A high content of water-insoluble fiber favorably influenced the appearance as well as the applicability of the products. PMID:11456292

  16. Integrated catalytic wet air oxidation and biological treatment of wastewater from Vitamin B 6 production

    NASA Astrophysics Data System (ADS)

    Kang, Jianxiong; Zhan, Wei; Li, Daosheng; Wang, Xiaocong; Song, Jing; Liu, Dongqi

    This study investigated the feasibility of coupling a catalytic wet air oxidation (CWAO), with CuO/Al 2O 3 as catalyst, and an anaerobic/aerobic biological process to treat wastewater from Vitamin B 6 production. Results showed that the CWAO enhanced the biodegradability (BOD 5/COD) from 0.10 to 0.80. The oxidized effluents with COD of 10,000 mg l -1 was subjected to subsequent continuous anaerobic/aerobic oxidation, and 99.3% of total COD removal was achieved. The quality of the effluent obtained met the discharge standards of water pollutants for pharmaceutical industry Chemical Synthesis Products Category (GB21904-2008), and thereby it implies that the integrated CWAO and anaerobic/aerobic biological treatment may offer a promising process to treat wastewater from Vitamin B 6 production.

  17. Rabies vaccination for international travelers.

    PubMed

    Gautret, Philippe; Parola, Philippe

    2012-01-01

    Rabies prevention in travelers is a controversial issue. According to experts, the decision to vaccinate results from an individual risk assessment based on the duration of stay, the likelihood of engagement in at-risk activities, the age of the traveler, the rabies endemicity and access to appropriate medical care in the country of destination. However, no detailed information is available regarding the last two determinants in many regions. Twenty-two cases of rabies were reported in tourists, expatriates and migrant travelers over the last decade, including three cases following short-term travel of no more than two weeks. Studies on rabies post-exposure prophylaxis (PEP) in travelers show that overall, 0.4% (range 0.01-2.3%) of travelers have experienced an at-risk bite per month of stay in a rabies-endemic country, while 31% of expatriates and 12% of tourists were vaccinated against rabies before traveling. The main reason cited by travelers for not being vaccinated is the cost of the vaccine. The majority of patients who sustained a high risk injury was not vaccinated against rabies before traveling and were not properly treated abroad. From available studies, the following risk factors for injuries sustained from potentially rabid animals may be identified: traveling to South-East Asia, India or North Africa, young age, and traveling for tourism. The duration of travel does not appear to be a risk factor. It should be noted that "at-risk activities" have not been addressed in these studies. Detailed rabies distribution maps and information on the availability of rabies biologics are urgently needed in order to identify those travelers who need pre-travel vaccination. Meanwhile, cost-minimization of rabies pre-exposure vaccination may be achieved in several ways, notably by using the intra-dermal method of vaccination. PMID:22085557

  18. Informed consent should be obtained from patients to use products (skin substitutes) and dressings containing biological material

    PubMed Central

    Enoch, S; Shaaban, H; Dunn, K

    2005-01-01

    Background: Biological products (tissue engineered skin, allograft and xenograft, and biological dressings) are widely used in the treatment of burns, chronic wounds, and other forms of acute injury. However, the religious and ethical issues, including consent, arising from their use have never been addressed in the medical literature. Aims: This study was aimed to ascertain the views of religious leaders about the acceptability of biological products and to evaluate awareness among healthcare professionals about their constituents. Methods: The religious groups that make up about 75% of the United Kingdom population were identified and a questionnaire on 11 biological products was sent to its leaders. Another questionnaire concerning 17 products (11 biological and 6 synthetic dressings) was sent to 100 healthcare professionals working in seven specialist units in the UK. Results: All religious leaders (100% response rate) replied, some after consultation with international bodies. Among them, 77% said that patients should be informed of the constituents of the biological products and consent obtained. Some leaders expressed concerns about particular products including the transmission of viral and prion diseases, cruelty to animals, and material derived from neonates. None of the healthcare professionals (73% response rate) surveyed knew the constituents of all the products correctly. Conclusion: Ignoring religious sensitivities and neglecting consent in the usage of biological products could have very serious implications, including litigation. Hospitals and manufacturers should take immediate measures to enlighten healthcare professionals of the constituents of these products so that they can obtain informed consent from patients. PMID:15634745

  19. Replicating vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early work on fish immunology and disease resistance demonstrated fish (like animals and humans) that survived infection were typically resistant to re-infection with the same pathogen. The concepts of resistance upon reinfection lead to the research and development of replicating (live) vaccines in...

  20. AIDS Vaccines.

    ERIC Educational Resources Information Center

    Matthews, Thomas J.; Bolognesi, Dani P.

    1988-01-01

    Reveals that success of discovering vaccines is far from being assured although several candidates are being tested. States that the devious nature of the virus, the lack of a good animal model for the disease, and the difficulties of clinical trials inhibit the efforts of researchers. (RT)

  1. Conformational and Thermal Stability Improvements for the Large-Scale Production of Yeast-Derived Rabbit Hemorrhagic Disease Virus-Like Particles as Multipurpose Vaccine

    PubMed Central

    Méndez, Lídice; González, Nemecio; Parra, Francisco; Martín-Alonso, José M.; Limonta, Miladys; Sánchez, Kosara; Cabrales, Ania; Estrada, Mario P.; Rodríguez-Mallón, Alina; Farnós, Omar

    2013-01-01

    Recombinant virus-like particles (VLP) antigenically similar to rabbit hemorrhagic disease virus (RHDV) were recently expressed at high levels inside Pichia pastoris cells. Based on the potential of RHDV VLP as platform for diverse vaccination purposes we undertook the design, development and scale-up of a production process. Conformational and stability issues were addressed to improve process control and optimization. Analyses on the structure, morphology and antigenicity of these multimers were carried out at different pH values during cell disruption and purification by size-exclusion chromatography. Process steps and environmental stresses in which aggregation or conformational instability can be detected were included. These analyses revealed higher stability and recoveries of properly assembled high-purity capsids at acidic and neutral pH in phosphate buffer. The use of stabilizers during long-term storage in solution showed that sucrose, sorbitol, trehalose and glycerol acted as useful aggregation-reducing agents. The VLP emulsified in an oil-based adjuvant were subjected to accelerated thermal stress treatments. None to slight variations were detected in the stability of formulations and in the structure of recovered capsids. A comprehensive analysis on scale-up strategies was accomplished and a nine steps large-scale production process was established. VLP produced after chromatographic separation protected rabbits against a lethal challenge. The minimum protective dose was identified. Stabilized particles were ultimately assayed as carriers of a foreign viral epitope from another pathogen affecting a larger animal species. For that purpose, a linear protective B-cell epitope from Classical Swine Fever Virus (CSFV) E2 envelope protein was chemically coupled to RHDV VLP. Conjugates were able to present the E2 peptide fragment for immune recognition and significantly enhanced the peptide-specific antibody response in vaccinated pigs. Overall these results allowed establishing improved conditions regarding conformational stability and recovery of these multimers for their production at large-scale and potential use on different animal species or humans. PMID:23460801

  2. Immunology of Vaccine Adjuvants

    Microsoft Academic Search

    C. M. S. Ribeiro; V. E. J. C. Schijns

    2010-01-01

    In recent times vaccine adjuvants, or immunopotentiators, received abundant attention in the media as critical ingredients of current and future vaccines. Indeed, vaccine adjuvants are recognized to make the difference between competing vaccines based on identical antigens. Moreover, it is recognized that vaccines designed for certain indications require a matching combination of selected antigen(s) together with a critical immunopotentiator that

  3. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M

    2013-01-01

    DNA vaccine for T1D promising in the clinic HPV vaccines halved infections in US teenage girls Modified DC immunotherapy against melanoma New study looks at clinical severity of human H7N9 infections Prevnar vaccines are valuable for healthcare systems GAPVAC: New consortium in the fight of brain cancer Cytomegalovirus vaccine to enter phase 3 Malaria vaccination using chemically attenuated parasites

  4. Combination vaccines: choices or chaos? A practitioner's perspective.

    PubMed

    Le, C T

    2001-12-15

    Combination vaccines are necessary and important for the continuing success of our immunization program, especially when more vaccines are added to the already crowded immunization schedule. However, the multiplicity of competing vaccine products, with various overlapping antigen menu and subtle immunologic differences, may be confusing to the busy practitioner. The cost-effectiveness of the use of combination vaccines will depend on a number of factors, including fair and competitive pricing, appropriate reimbursement for vaccine administration fees, and critical economic algorithms for vaccine selection and purchase. PMID:11709775

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

    PubMed

    Go?o?, Aleksandra; Luty?ska, Anna

    2015-01-01

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

  6. Meat Production in a Feedlot System of Zebu—Holstein Steers and Heifers with Dairy Genetics: Productive and Biological Analyses

    PubMed Central

    Menezes, Gustavo Chamon de Castro; Valadares Filho, Sebastião de Campos; Ruas, José Reinaldo Mendes; Detmann, Edenio; Menezes, Arismar de Castro; Zanett, Diego; Mariz, Lays Débora Silva; Rennó, Luciana Navajas; da Silva Junior, Jarbas Miguel

    2014-01-01

    The aim of this study was to evaluate the productive and biological efficiency of steers and heifers from dairy genetics in a feedlot system in terms of meat production. Twenty-four steers and 24 heifers at 10 monthes of age, (3/4) Zebu × (1/4) Holstein were utilized. They were distributed over four feedlot times, 30, 60, 90, and 120 days with four replications for each sex, and were slaughtered at the end of each period. The productive and biological analyses were performed through comparative slaughter to determine the body composition. Heifers presented with greater intakes (P < 0.05) of dry matter in grams per kg of body weight. Steers presented with a greater (P < 0.05) final empty body weight, carcass gain, cold carcass weight, and meat proportion in the carcass; however, heifers presented with a greater subcutaneous fat thickness (P < 0.05) and, consequently, a greater (P < 0.05) fat proportion in the carcass. We conclude that steers are more efficient in their productive performance than heifers in a feedlot. For the finishing carcass fat cover, heifers need 90 days in the feedlot. The net energy requirements for maintenance are 67?kcal/EBW0.75/d, and the net requirements of energy (NEg) and protein (NPg) for gain can be estimated by the following equations: NEg(Mcal/d) = 0.067 × EBW0.75 × EBG1.095 and NPg = 162 × EBG ? 5.62 × RE for the two sexes. PMID:25574483

  7. Current development in non-enzymatic lipid peroxidation products, isoprostanoids and isofuranoids, in novel biological samples.

    PubMed

    Leung, K S; Galano, J M; Durand, T; Lee, J C-Y

    2015-07-01

    Isoprostanoids and isofuranoids are lipid mediators that can be formed from omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). F2-isoprostanes formed from arachidonic acid, especially 15-F2t-isoprostane, are commonly measured in biological tissues for decades as the biomarker for oxidative stress and diseases. Recently, other forms of isoprostanoids derived from adrenic, eicosapentaenoic, and docosahexaenoic acids namely F2-dihomo-isoprostanes, F3-isoprostanes, and F4-neuroprostanes respectively, and isofuranoids including isofurans, dihomo-isofurans, and neurofurans are reported as oxidative damage markers for different metabolisms. The most widely used samples in measuring lipid peroxidation products include but not limited to the blood and urine; other biological fluids, specialized tissues, and cells can also be determined. In this review, measurement of isoprostanoids and isofuranoids in novel biological samples by gas chromatography (GC)-mass spectrometry (MS), GC-MS/MS, liquid chromatography (LC)-MS, and LC-MS/MS will be discussed. PMID:25184341

  8. BIOLOG

    EPA Science Inventory

    BIOLOG contains more than 43,000 citations to literature on microbial degradation and toxicity of more than 6,000 chemicals. Records are organized by CAS Registry Number and by 6 categories (i.e., biodegradation/toxicity; oxygen condition (anaerobic/aerobic); culture type (pure e...

  9. Vaccinations in patients with immune-mediated inflammatory diseases

    PubMed Central

    Rahier, Jean-François; Moutschen, Michel; Van Gompel, Alfons; Van Ranst, Marc; Louis, Edouard; Segaert, Siegfried; Masson, Pierre

    2010-01-01

    Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals. PMID:20591834

  10. Application of Risk Assessments in the Design of the Overall Viral Control Strategy Used during the Manufacture and Testing of Live Virus Vaccines.

    PubMed

    Pennathur, Sridhar

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) It is important to include a risk assessment process in the overall viral control strategy used during the manufacture and testing of live virus vaccines. Because the product is itself a virus, traditional viral clearance steps are generally not included in the manufacturing process, and there is normally no inactivation step in the manufacturing process either. The risk assessment is therefore necessary to identify potential sources for entry of adventitious agents into the vaccine, and to develop a strategy to minimize or eliminate the sources through which adventitious agents can enter the vaccine. The risk assessment can also be used to tailor the biosafety testing that is performed on raw materials, vaccine seeds, vaccine bulk materials, and final product. Biosafety testing is normally designed to ensure the detection of both known and unknown adventitious agents, but the results of the risk assessment can be used to put in place a biosafety testing strategy designed to maximize the detection of an adventitious agent that is potentially likely to be present in the vaccine. The risk assessment therefore enables the development of a comprehensive viral control strategy and provides a higher level of assurance that the vaccine will be free from contamination by adventitious agents. PMID:22294607

  11. Impact of BRICS' investment in vaccine development on the global vaccine market.

    PubMed

    Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah

    2014-06-01

    Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018

  12. Dire necessity and transformation: entry-points for modern science in Islamic bioethical assessment of porcine products in vaccines.

    PubMed

    Padela, Aasim I; Furber, Steven W; Kholwadia, Mohammad A; Moosa, Ebrahim

    2014-02-01

    The field of medicine provides an important window through which to examine the encounters between religion and science, and between modernity and tradition. While both religion and science consider health to be a 'good' that is to be preserved, and promoted, religious and science-based teachings may differ in their conception of what constitutes good health, and how that health is to be achieved. This paper analyzes the way the Islamic ethico-legal tradition assesses the permissibility of using vaccines that contain porcine-derived components by referencing opinions of several Islamic authorities. In the Islamic ethico-legal tradition controversy surrounds the use of proteins from an animal (pig) that is considered to be impure by Islamic law. As we discuss the Islamic ethico-legal constructs used to argue for or against the use of porcine-based vaccines we will call attention to areas where modern medical data may make the arguments more precise. By highlighting areas where science can buttress and clarify the ethico-legal arguments we hope to spur an enhanced applied Islamic bioethics discourse where religious scholars and medical experts use modern science in a way that remains faithful to the epistemology of Islamic ethics to clarify what Islam requires of Muslim patients and healthcare workers. PMID:23445524

  13. Progress and pitfalls in Shigella vaccine research

    PubMed Central

    Barry, Eileen M.; Pasetti, Marcela F.; Sztein, Marcelo B.; Fasano, Alessio; Kotloff, Karen L.; Levine, Myron M.

    2013-01-01

    Renewed awareness of the significant morbidity and mortality that Shigella causes among young children in developing countries combined with technological innovations in vaccinology has led to the development of novel vaccine strategies in the past five years. Along with advancement of classical vaccines in clinical trials and new sophisticated measurements of immunological responses, much new data has been produced lending promise to the potential for production of safe and effective Shigella vaccines. Herein we review the recent progress in Shigella vaccine development within the framework of persistent obstacles. PMID:23419287

  14. A synthetic peptide vaccine involving the product of the pre-S(2) region of hepatitis B virus DNA: protective efficacy in chimpanzees.

    PubMed Central

    Itoh, Y; Takai, E; Ohnuma, H; Kitajima, K; Tsuda, F; Machida, A; Mishiro, S; Nakamura, T; Miyakawa, Y; Mayumi, M

    1986-01-01

    The S gene encoding the major surface polypeptide of hepatitis B virus is preceded by the region pre-S(2) with a capacity to code for 55 amino acid residues. In the product of region pre-S(2), the sequence of 19 amino acid residues (amino acids 14-32 from the N terminus) representing an area of high local hydrophilicity is shared by viral strains of subtypes adr, ayw, and ayr; residue 22, phenylalanine, is replaced by leucine in a strain of the other subtype, adw. A synthetic peptide vaccine involving these 19 amino acid residues, when given to two chimpanzees, raised antibodies that bound to viral particles and protected the animals from challenge with 10(6) chimpanzee infectious doses of hepatitis B virus. Images PMID:3466181

  15. Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products.

    PubMed

    Frevert, Jürgen

    2015-03-01

    Botulinum neurotoxin injections are a valuable treatment modality for many therapeutic indications and have revolutionized the field of aesthetic medicine so that they are the leading cosmetic procedure performed worldwide. Studies show that onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA are comparable in terms of clinical efficacy. Differences between the products relate to the botulinum neurotoxin complexes, specific biological potency, and their immunogenicity. Protein complex size and molecular weight have no effect on biological activity, stability, distribution, or side effect profile. Complexing proteins and inactive toxin (toxoid) content increase the risk of neutralizing antibody formation, which can cause secondary treatment failure, particularly in chronic disorders that require frequent injections and long-term treatment. These attributes could lead to differences in therapeutic outcomes, and, given the widespread aesthetic use of these three neurotoxin products, physicians should be aware of how they differ to ensure their safe and effective use. PMID:25559581

  16. Developing mRNA-vaccine technologies.

    PubMed

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

    2012-11-01

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

  17. [Vaccines, immunization and technological innovation: an update].

    PubMed

    Homma, Akira; Martins, Reinaldo de Menezes; Leal, Maria da Luz Fernandes; Freire, Marcos da Silva; Couto, Artur Roberto

    2011-02-01

    The smallpox worldwide eradication was the major world public health achievement. The binomial - vaccines and immunization - continues to demonstrate very high performance in the prevention and control of other diseases preventable by vaccination. The new global initiatives on vaccination, such as GAVI, have made possible the introduction of new and important vaccines preventing million of children deaths in the poorest countries in the world. The National Immunization Program of Brazil is also being strengthened, with the introduction of several new vaccines into the basic calendar as rotavirus, pneumococcal and meningococcal conjugated and H1N1 in national campaign, covering the population at risk. With the discovery of high valued vaccines, the big pharmaceutical companies became interested in this area, investing heavily in technological innovation, making fusions, acquisitions and technological partnerships. Brazil has also established a new innovation policy, creating new laws as well as subsidizing projects in technological innovation and modernization of production infra-structure. PMID:21340320

  18. First generation leishmaniasis vaccines: A review of field efficacy trials

    Microsoft Academic Search

    Sassan Noazin; Farrokh Modabber; Ali Khamesipour; Peter G. Smith; Lawrence H. Moulton; Kiumarss Nasseri; Iraj Sharifi; Eltahir A. G. Khalil; Ivan Dario Velez Bernal; Carlos M. F. Antunes; Marie Paule Kieny; Marcel Tanner

    2008-01-01

    First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated

  19. Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis.

    PubMed

    Kaye, P M; Curry, A J; Blackwell, J M

    1991-04-15

    Recent studies with models of cutaneous leishmaniasis have provoked much interest in the role of CD4+ T cell subsets in determining the outcome of infectious disease. In Leishmania major infections, cure vs progressive disease correlates with the expansion of Th1-like or Th2-like CD4+ populations, respectively. We have investigated whether similar responses are associated with the differential patterns of infection seen in models of visceral leishmaniasis, caused by L. donovani. Splenic lymphocytes from infected Lsh congenic C57BL/10 (Lshs;H-2b) and B10.L-Lshr (Lshr;H-2b) mice and MHC congenic non-curing B10.D2/n (Lshs;H-2d) mice were examined for the production of cytokines representative of these CD4+ populations (IL-2, IL-3, IL-4, IL-5, and IFN-gamma). In all three strains examined, there was no evidence for the production of Th2-restricted cytokines. In addition, levels of serum IgE were depressed during the early phase of infection, indicative of in vivo IFN-gamma production. In the non-curing B10.D2/n strain, late phase of infection was associated with the decreased ability to produce cytokines in response to Ag and not with the production of IL-4 or IL-5 in response to Ag or mitogen. Serum IgE levels were also not raised above levels seen in uninfected controls. C57BL/10 mice were vaccinated with SDS-PAGE fractionated amastigote Ag bound to nitrocellulose and cytokine levels determined at various times after infection. The protocol used for vaccination was able to induce significant modulation of the course of infection in this strain and it was clear that IFN-gamma production in vitro provided an excellent correlate of rate of cure. Occasional individuals produced low levels of IL-5 in culture in response to parasite Ag, but this did not correlate with disease progression. Together, these data suggest that over-expansion of Th2-type cells and production of their specific cytokines (IL-4 and IL-5) is not a contributing factor to the variable long term course of L. donovani infection in these strains of mice. PMID:1901883

  20. Vaccines for Pregnant Women

    MedlinePLUS

    ... lifestyle, medical conditions you may have, such as asthma or diabetes, type and locations of travel, and previous vaccinations. See the Immunization and Pregnancy Vaccines Flyer [1 page] , which shows the vaccines ...

  1. Vaccinations and HIV

    MedlinePLUS

    ... Do not measure your viral load within 4 weeks of any vaccination. Flu shots have been studied ... live” vaccination in the past 2 or 3 weeks. Still, the “MMR” vaccine against measles, mumps and ...

  2. Size analysis of residual host cell DNA in cell culture-produced vaccines by capillary gel electrophoresis.

    PubMed

    Shen, Xuan; Chen, Xiaomu; Tabor, David E; Liu, Yi; Albarghouthi, Methal; Zhang, Yi-Fan; Galinski, Mark S

    2013-05-01

    Residual host cell DNA poses potential safety concerns for cell culture-derived vaccines or other biological products. In addition to the quantity of residual DNA, the size distribution is an important measure for determination of its associated risk factor. We have developed a new method for residual DNA size analysis, based on capillary gel electrophoresis (CGE) technology with sensitive laser induced fluorescence detection (LIF). The performance of this method was optimized through empirical selection of appropriate testing conditions and optimized conditions are presented. Examples are given to demonstrate the successful employment of this method for residual DNA size analysis of cell culture-produced vaccine samples. PMID:23313102

  3. Delivering vaccines to the people who need them most.

    PubMed

    Barocchi, Michèle Anne; Rappuoli, Rino

    2015-06-19

    Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine Fund and the Bill & Melinda Gates Foundation, the global health community has made enormous progress in providing already existing vaccines to developing countries. However, there still exists a gap to develop vaccines for which there is no market in the Western world, owing to low economic incentives for the private sector to justify the investments necessary for vaccine development. In many cases, industry has the technologies, but lacks the impetus to direct resources to develop these vaccine products. The present emergency with the Ebola vaccine provides us an excellent example where a vaccine was feasible several years ago, but the global health community waited for a humanitarian disaster to direct efforts and resources to develop this vaccine. In the beginning of 2015, the first large-scale trials of two experimental vaccines against Ebola virus disease have begun in West Africa. During the past few years, several institutions have dedicated efforts to the development of vaccines against diseases present only in low-income countries. These include the International Vaccine Institute, the Novartis Vaccines Institute for Global Health, the Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease Research Institute. Nevertheless, solving this problem requires a more significant global effort than that currently invested. These efforts include a clear policy, global coordination of funds dedicated to the development of neglected disease and an agreement on regulatory strategies and incentives for the private sector. PMID:25964460

  4. Subviral Particle as Vaccine and Vaccine Platform

    PubMed Central

    Tan, Ming; Jiang, Xi

    2014-01-01

    Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts. PMID:24662314

  5. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. (Mount Sinai Hospital, Toronto, Ontario (Canada). Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  6. Human Vaccines & Immunotherapeutics: News

    PubMed Central

    Riedmann, Eva M.

    2013-01-01

    Therapeutic HIV vaccine promising in the clinic GAVI aims to immunize 30 million against HPV by 2020 Self-destructing Salmonella to deliver oral DNA vaccines Novel strategy for vaccine design: Enzymatically modified antibodies GSK’s four-strain seasonal influenza vaccine approved in the US MVA85A TB vaccine tested in newborns of HIV-positive mothers Use of oral cholera vaccines promoted GSK partners with Vodafone to increase childhood vaccinatin in Mozambique PMID:23449312

  7. Potential of chicken by-products as sources of useful biological resources.

    PubMed

    Lasekan, Adeseye; Abu Bakar, Fatimah; Hashim, Dzulkifly

    2013-03-01

    By-products from different animal sources are currently being utilised for beneficial purposes. Chicken processing plants all over the world generate large amount of solid by-products in form of heads, legs, bones, viscera and feather. These wastes are often processed into livestock feed, fertilizers and pet foods or totally discarded. Inappropriate disposal of these wastes causes environmental pollution, diseases and loss of useful biological resources like protein, enzymes and lipids. Utilisation methods that make use of these biological components for producing value added products rather than the direct use of the actual waste material might be another viable option for dealing with these wastes. This line of thought has consequently led to researches on these wastes as sources of protein hydrolysates, enzymes and polyunsaturated fatty acids. Due to the multi-applications of protein hydrolysates in various branches of science and industry, and the large body of literature reporting the conversion of animal wastes to hydrolysates, a large section of this review was devoted to this subject. Thus, this review reports the known functional and bioactive properties of hydrolysates derived from chicken by-products as well their utilisation as source of peptone in microbiological media. Methods of producing these hydrolysates including their microbiological safety are discussed. Based on the few references available in the literature, the potential of some chicken by-product as sources of proteases and polyunsaturated fatty acids are pointed out along with some other future applications. PMID:22985619

  8. Construction of a microbial natural product library for chemical biology studies.

    PubMed

    Kato, Naoki; Takahashi, Shunji; Nogawa, Toshihiko; Saito, Tamio; Osada, Hiroyuki

    2012-04-01

    The RIKEN Natural Products Depository (NPDepo) is a public depository of small molecules. Currently, the NPDepo chemical library contains 39,200 pure compounds, half of which are natural products and their derivatives. In order to reinforce the uniqueness of our chemical library, we have improved our strategies for the collection of microbial natural products. Firstly, a microbial metabolite fraction library coupled with an MP (microbial products) plot database provides a powerful resource for the efficient isolation of microbial metabolites. Secondly, biosynthetic studies of microbial metabolites have enabled us to not only access ingenious biosynthetic machineries, but also obtain a variety of biosynthetic intermediates. Our chemical library contributes to the discovery of molecular probes for increasing our understanding of complex biological processes and for eventually developing new drug leads. PMID:22406171

  9. Smallpox vaccines: targets of protective immunity

    PubMed Central

    Moss, Bernard

    2011-01-01

    Summary The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second and third generation smallpox vaccines. PMID:21198662

  10. Vaccines for Farrowing Operations 

    E-print Network

    Lawhorn, D. Bruce

    1999-02-15

    Routine vaccination is necessary to control economically important swine diseases such as erysipelas, leptospirosis, parvovirus and colibacillosis. The symptoms and specific vaccines for these diseases are discussed....

  11. Nonreplicating vectors in HIV vaccines

    PubMed Central

    Johnson, JA; Barouch, DH; Baden, LR

    2014-01-01

    Purpose of review We review the broad spectrum of nonreplicating viral vectors which have been studied extensively, from preclinical studies through clinical efficacy trials, and include some of our most promising HIV vaccine candidates. Recent findings The success of the RV144 trial, with an ALVAC (canarypox)-based regimen, contrasts with the failures of the Adenovirus 5-based regimens in the Step study, the Phambili study (HVTN 503), and the HVTN 505 study which was recently modified to halt vaccinations due to clinical futility. Summary The safety profile, immunogenicity, and variety of available candidates make the nonreplicating viral vectors attractive in HIV vaccine development. Building from the success of the RV144 study, further studies of Orthopoxvirus-based vaccines, including Vaccinia-based vaccines, are ongoing and planned for the future. Despite the failures of the Ad5-based vaccines in clinical efficacy trials, other adenovirus serotypes remain promising candidates, especially in prime-boost combination with other products, and with the potential use of mosaic inserts. Other nonreplicating viral vectors such as the rhabdoviruses, alphaviruses and the non-human adenoviruses, provide additional avenues for exploration. PMID:23925001

  12. [Vaccination strategies for anthrax prevention].

    PubMed

    Beyer, Wolfgang

    2004-01-01

    Apart from live spore vaccines with a certain amount of residual virulence for various animal species, there are two acellular protein vaccines for immunoprophylaxis against anthrax in humans. For ethical reasons there are no experimental data available on the efficacy and duration of the immunity they induce in men. Their efficacy was evaluated in laboratory animals, mainly rabbits and rhesus monkeys. Furthermore, it is well known that these vaccines elicit only partial protection in guinea pigs and almost no protection in mice against a challenge with fully virulent spores of Bacillus (B.) anthracis. Other disadvantages are the high amount of boosters necessary to elicit and to maintain a protective immune response, the variability in the composition of bacterial culture supernatants used for production, and the appearance of clinically relevant side effects. Therefore, there is ongoing work worldwide to improve the existing vaccines by substitution with recombinant antigens and to develop new vaccines on the basis of recombinant bacterial or viral live vectors, DNA-vectors, and by addition of new adjuvants. Special attention is given to supplementing the existing toxoid-vaccines with an anti-bacterial component. PMID:15584433

  13. 71 FR 30938 - Vaccine Information Statement for Hepatitis A Vaccine; Revised Instructions for Use of Vaccine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2006-05-31

    ...Prevention Vaccine Information Statement for Hepatitis A Vaccine; Revised Instructions for...new vaccine information materials for hepatitis A vaccine. Following review of the comments...under the law, CDC has finalized the hepatitis A vaccine information materials....

  14. The Anthrax Vaccine Program: an analysis of the CDC's recommendations for vaccine use.

    PubMed

    Nass, Meryl

    2002-05-01

    The anthrax vaccine was never proved to be safe and effective. It is one cause of Gulf War illnesses, and recent vaccinees report symptoms resembling Gulf War illnesses. The vaccine's production has been substandard. Without adequate evaluation, the Food and Drug Administration recently approved (retrospectively) significant changes made to the vaccine's composition since 1990. The vaccine's mandatory use for inhalation anthrax is "off-label." A skewed review of the vaccine literature by the Centers for Disease Control and Prevention (CDC) led to remunerative collaborative research with the army, involving civilian volunteers. Despite acknowledging possible fetal harm, the CDC offered the vaccine to children and pregnant women. New trends could weaken prelicensure efficacy and safety review of medical products intended for biodefense and avoid manufacturer liability for their use. PMID:11988433

  15. Cytokine profile after rubella vaccine inoculation: evidence of the immunosuppressive effect of vaccination.

    PubMed Central

    Pukhalsky, Alexander L; Shmarina, Galina V; Bliacher, Maria S; Fedorova, Irina M; Toptygina, Anna P; Fisenko, Julia J; Alioshkin, Vladimir A

    2003-01-01

    BACKGROUND AND AIM: Immunization with live virus vaccines may cause an immunosuppression with lymphopaenia, impaired cytokine production and defective lymphocyte response to mitogenes. These abnormalities were described in subjects vaccinated against measles. This study was performed to analyse the host immune response related to immunosuppression in subjects vaccinated with live attenuated rubella vaccine. METHODS: Eighteen schoolgirls, aged 11-13 years, were vaccinated with live attenuated rubella vaccine Rudivax. Before immunization, and 7 and 30 days after, peripheral blood was collected. Cellular fractions were subjected to flow cytometric analysis, and the lymphocyte response to phytohaemagglutinin was investigated. Plasma samples were analysed for cytokines (interleukin (IL)-4, IL-10, tumour necrosis factor-alpha, and interferon-gamma) by enzyme-linked immunosorbent assay techniques. RESULTS: On day 7 after vaccination, the number of each lymphocyte subset was decreased; however, only for CD3 and CD4 lymphocytes has a significant reduction been shown. On the contrary, tumour necrosis factor-alpha and IL-10 levels markedly increased and amounted to its maximum on day 30. Simultaneously, a significant reduction in plasma interferon-gamma and a profound decrease of the lymphocyte response to phytohaemagglutinin were shown. The changes were accompanied with marked elevation of plasma IL-4. CONCLUSIONS: Our data indicate that the vaccination with live attenuated rubella vaccine results in moderate but sustained immune disturbance. The signs of immunosuppression, including defective lymphocyte response to mitogene and impaired cytokine production, may persist for at least 1 month after vaccination. PMID:14514470

  16. Antiviral Cationic Peptides as a Strategy for Innovation in Global Health Therapeutics for Dengue Virus: High Yield Production of the Biologically Active Recombinant Plectasin Peptide

    PubMed Central

    Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M.; Rahman, Noorsaadah Abd; Yusof, Rohana

    2013-01-01

    Abstract Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20??M (100??g/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03±0.98??M. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection. PMID:24044366

  17. Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide.

    PubMed

    Rothan, Hussin A; Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M; Rahman, Noorsaadah Abd; Yusof, Rohana

    2013-11-01

    Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20??M (100??g/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98??M. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection. PMID:24044366

  18. Trends affecting the future of vaccine development and delivery: The role of demographics, regulatory science, the anti-vaccine movement, and vaccinomics

    Microsoft Academic Search

    Gregory A. Poland; Robert M. Jacobson; Inna G. Ovsyannikova

    2009-01-01

    Important scientific, cultural, temporal, and secular issues impact the development of, and delivery of vaccines. In this paper we discuss the impact of demographics, regulatory science, the anti-vaccine movement, and finally the impact of the new biology and individualized medicine, which we call vaccinomics, on vaccine development and delivery. A description of the issues and how they have, are, or

  19. How do we assure the quality of biological medicines?

    PubMed

    Longstaff, Colin; Whitton, Colin M; Stebbings, Richard; Gray, Elaine

    2009-01-01

    Biological medicines are a rapidly growing area of interest to many pharmaceutical companies, large and small. Under a broad definition they include not only modern high-tech products, such as monoclonal antibodies, enzymes and cytokines, but also older well-established products, such as vaccines and blood products. Despite a long history of standardisation and control of biological medicines, and an elaborate system of licensing and regulation, problems still occur because of their complexity. This review includes historical and regulatory background and three examples of problems seen with biotherapeutics: streptokinase, heparin and TGN1412. PMID:18951998

  20. [Vaccination and pregnancy].

    PubMed

    Anselem, Olivia; Parat, Sophie; Théau, Anne; Floret, Daniel; Tsatsaris, Vassilis; Goffinet, François; Launay, Odile

    2014-06-01

    Vaccination against influenza is recommended during the vaccination period in pregnant women regardless of trimester. In contrast, administration of live vaccines, such as the vaccine against varicella, MMR (measles-mumps-rubella) is contraindicated in pregnant women. Vaccinations against hepatitis B, diphtheria, tetanus, poliomyelitis, hepatitis A can be made as indicated. Vaccination against yellow fever may be considered in pregnant women travelling to endemic countries. In post-partum period, live vaccines may be administered if necessary, especially vaccination against whooping cough for women not to date with their vaccinations. Vaccination against yellow fever is contraindicated in case of breast feeding. Prevention of pertussis in newborns is based in France on vaccination of the mothers in the post-partum period, and the close contacts of the newborn during the pregnancy ("cocooning"). PMID:24863661

  1. Biological Pretreatment of Rubberwood with Ceriporiopsis subvermispora for Enzymatic Hydrolysis and Bioethanol Production

    PubMed Central

    Nazarpour, Forough; Abdullah, Dzulkefly Kuang; Abdullah, Norhafizah; Motedayen, Nazila; Zamiri, Reza

    2013-01-01

    Rubberwood (Hevea brasiliensis), a potential raw material for bioethanol production due to its high cellulose content, was used as a novel feedstock for enzymatic hydrolysis and bioethanol production using biological pretreatment. To improve ethanol production, rubberwood was pretreated with white rot fungus Ceriporiopsis subvermispora to increase fermentation efficiency. The effects of particle size of rubberwood (1?mm, 0.5?mm, and 0.25?mm) and pretreatment time on the biological pretreatment were first determined by chemical analysis and X-ray diffraction and their best condition obtained with 1?mm particle size and 90 days pretreatment. Further morphological study on rubberwood with 1 mm particle size pretreated by fungus was performed by FT-IR spectra analysis and SEM observation and the result indicated the ability of this fungus for pretreatment. A study on enzymatic hydrolysis resulted in an increased sugar yield of 27.67% as compared with untreated rubberwood (2.88%). The maximum ethanol concentration and yield were 17.9?g/L and 53% yield, respectively, after 120 hours. The results obtained demonstrate that rubberwood pretreated by C. subvermispora can be used as an alternative material for the enzymatic hydrolysis and bioethanol production. PMID:24167813

  2. Laser-initiated decomposition products of indocyanine green (ICG) and carbon black sensitized biological tissues

    NASA Astrophysics Data System (ADS)

    Kokosa, John M.; Przyjazny, Andrzej; Bartels, Kenneth E.; Motamedi, Massoud; Hayes, Donald J.; Wallace, David B.; Frederickson, Christopher J.

    1997-05-01

    Organic dyes have found increasing use a s sensitizers in laser surgical procedures, due to their high optical absorbances. Little is known, however, about the nature of the degradation products formed when these dyes are irradiated with a laser. Previous work in our laboratories has shown that irradiation of polymeric and biological tissues with CO2 and Nd:YAG lasers produces a host of volatile and semivolatile by-products, some of which are known to be potential carcinogens. This work focuses on the identification of the chemical by-products formed by diode laser and Nd:YAG laser irradiation of indocyanine green (ICG) and carbon black based ink sensitized tissues, including bone, tendon and sheep's teeth. Samples were mounted in a 0.5-L Pyrex sample chamber equipped with quartz optical windows, charcoal filtered air inlet and an outlet attached to an appropriate sample trap and a constant flow pump. By-products were analyzed by GC/MS and HPLC. Volatiles identified included benzene and formaldehyde. Semi-volatiles included traces of polycyclic aromatics, arising from the biological matrix and inks, as well as fragments of ICG and the carbon ink components. The significance of these results will be discussed, including the necessity of using appropriate evacuation devices when utilizing lasers for surgical procedures.

  3. Respiratory syncytial virus vaccine development

    PubMed Central

    Hurwitz, Julia L

    2011-01-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral disease in infants and young children. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. The virus is therefore responsible for an estimated 160,000 deaths per year worldwide. Despite half a century of dedicated research, there remains no licensed vaccine product. Herein are described past and current efforts to harness innate and adaptive immune potentials to combat RSV. A plethora of candidate vaccine products and strategies are reviewed. The development of a successful RSV vaccine may ultimately stem from attention to historical lessons, in concert with an integral partnering of immunology and virology research fields. PMID:21988307

  4. Developing live vaccines against Yersinia pestis

    PubMed Central

    Sun, Wei; Roland, Kenneth L.; Curtiss, Roy

    2014-01-01

    Three great plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people and it has been linked to biowarfare in the past. Plague is endemic in many parts of the world. In addition, the risk of plague as a bioweapon has prompted increased research to develop plague vaccines against this disease. Injectable subunit vaccines are being developed in the United States and United Kingdom. However, the live attenuated Y. pestis-EV NIIEG strain has been used as a vaccine for more than 70 years in the former Soviet Union and in some parts of Asia and provides a high degree of efficacy against plague. This vaccine has not gained general acceptance because of safety concerns. In recent years, modern molecular biological techniques have been applied to Y. pestis to construct strains with specific defined mutations designed to create safe, immunogenic vaccines with potential for use in humans and as bait vaccines to reduce the load of Y. pestis in the environment. In addition, a number of live, vectored vaccines have been reported using attenuated viral vectors or attenuated Salmonella strains to deliver plague antigens. Here we summarize the progress of live attenuated vaccines against plague. PMID:21918302

  5. An international technology platform for influenza vaccines.

    PubMed

    Hendriks, Jan; Holleman, Marit; de Boer, Otto; de Jong, Patrick; Luytjes, Willem

    2011-07-01

    Since 2008, the World Health Organization has provided seed grants to 11 manufacturers in low- and middle-income countries to establish or improve their pandemic influenza vaccine production capacity. To facilitate this ambitious project, an influenza vaccine technology platform (or "hub") was established at the Netherlands Vaccine Institute for training and technology transfer to developing countries. During its first two years of operation, a robust and transferable monovalent pilot process for egg-based inactivated whole virus influenza A vaccine production was established under international Good Manufacturing Practice standards, as well as in-process and release assays. A course curriculum was designed, including a two-volume practical handbook on production and quality control. Four generic hands-on training courses were successfully realized for over 40 employees from 15 developing country manufacturers. Planned extensions to the curriculum include cell-culture based technology for viral vaccine production, split virion influenza production, and generic adjuvant formulation. We conclude that technology transfer through the hub model works well, significantly builds vaccine manufacturing capacity in developing countries, and thereby increases global and equitable access to vaccines of high public health relevance. PMID:21684431

  6. Mass and energy balance constraints on the biological production of chemicals from coal

    SciTech Connect

    Andrews, G.

    1990-01-01

    Several organic chemicals, including methane and ethanol, may be produced by the bioprocessing of coal. This may be done either by direct microbial attack on the coal, or indirectly by the bioprocessing of solubilized coal. As in chemical liquefaction and gasification, the relative amounts of the various products that can be produced are severely constrained by mass and energy balance considerations. The main differences in biological processing are that water is a ubiquitous reactant, carbon dioxide a common product, and that some of the carbon and nitrogen in the coal may go to the synthesis of new biomass rather than products. The conventional biotechnological yield analysis applied to coal processing has several interesting consequences. The mass balance reduces to a balance of available electrons, and coal has a similar oxidation/reduction state to both carbohydrates and biomass. This makes high product yields feasible particularly under anaerobic conditions, although leaving open the question of whether the relevant hydrolase enzymes exist. Recommendations are made on products, and combinations of two products, that may be made with high yields and economic return. The energy balance provides little extra information. A general intracellular energy balance can be written in terms of the production and consumption of ATP, but much of the necessary information on the metabolic pathways is currently not available for coal processing microorganisms. 9 refs., 2 figs., 2 tabs.

  7. A review of biological delignification and detoxification methods for lignocellulosic bioethanol production.

    PubMed

    Moreno, Antonio D; Ibarra, David; Alvira, Pablo; Tomás-Pejó, Elia; Ballesteros, Mercedes

    2014-02-10

    Abstract Future biorefineries will integrate biomass conversion processes to produce fuels, power, heat and value-added chemicals. Due to its low price and wide distribution, lignocellulosic biomass is expected to play an important role toward this goal. Regarding renewable biofuel production, bioethanol from lignocellulosic feedstocks is considered the most feasible option for fossil fuels replacement since these raw materials do not compete with food or feed crops. In the overall process, lignin, the natural barrier of the lignocellulosic biomass, represents an important limiting factor in biomass digestibility. In order to reduce the recalcitrant structure of lignocellulose, biological pretreatments have been promoted as sustainable and environmentally friendly alternatives to traditional physico-chemical technologies, which are expensive and pollute the environment. These approaches include the use of diverse white-rot fungi and/or ligninolytic enzymes, which disrupt lignin polymers and facilitate the bioconversion of the sugar fraction into ethanol. As there is still no suitable biological pretreatment technology ready to scale up in an industrial context, white-rot fungi and/or ligninolytic enzymes have also been proposed to overcome, in a separated or in situ biodetoxification step, the effect of the inhibitors produced by non-biological pretreatments. The present work reviews the latest studies regarding the application of different microorganisms or enzymes as useful and environmentally friendly delignification and detoxification technologies for lignocellulosic biofuel production. This review also points out the main challenges and possible ways to make these technologies a reality for the bioethanol industry. PMID:24506661

  8. Effectiveness of vaccines and vaccination programs for the control of foot-and-mouth disease in Uganda, 2001-2010.

    PubMed

    Muleme, Michael; Barigye, Robert; Khaitsa, Margaret L; Berry, Eugene; Wamono, Anthony W; Ayebazibwe, Chrisostom

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. In Uganda, FMD outbreaks are mainly controlled by ring vaccination and restriction of animal movements. Vaccination stimulates immunity and prevents animals from developing clinical signs which include lameness, inappetence, and decreased production. Ring vaccination and restriction of animal movements have, however, not successfully controlled FMD in Uganda and outbreaks reoccur annually. The objective of this study was to review the use of FMD virus (FMDV) vaccines and assess the effectiveness of vaccination programs for controlling FMD in Uganda (2001-2010), using retrospective data. FMD vaccine distribution patterns in Uganda (2001-2010) matched occurrence of outbreaks with districts reporting the highest number of outbreaks also receiving the largest quantity of vaccines. This was possibly due to "fire brigade" response of vaccinating animals after outbreaks have been reported. On average, only 10.3 % of cattle within districts that reported outbreaks during the study period were vaccinated. The average minimum time between onset of outbreaks and vaccination was 7.5 weeks, while the annual cost of FMDV vaccines used ranged from US $58,000 to 1,088,820. Between 2001 and 2010, serotyping of FMD virus was done in only 9/121 FMD outbreaks, and there is no evidence that vaccine matching or vaccine potency tests have been done in Uganda. The probability of FMDV vaccine and outbreak mismatch, the delayed response to outbreaks through vaccination, and the high costs associated with importation of FMDV vaccines could be reduced if virus serotyping and subtyping as well as vaccine matching were regularly done, and the results were considered for vaccine manufacture. PMID:22956440

  9. Protection against infectious laryngotracheitis by in ovo vaccination with commercially available viral vector recombinant vaccines.

    PubMed

    Johnson, Deirdre I; Vagnozzi, Ariel; Dorea, Fernanda; Riblet, Sylva M; Mundt, Alice; Zavala, Guillermo; García, Maricarmen

    2010-12-01

    Infectious laryngotracheitis (ILT) is a highly contagious respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). The disease is mainly controlled through biosecurity and by vaccination with live-attenuated vaccines. The chicken embryo origin (CEO) vaccines, although proven to be effective in experimental settings, have limited efficacy in controlling the disease in dense broiler production sites due to unrestricted use and poor mass vaccination coverage. These factors allowed CEO vaccines to regain virulence, causing long lasting and, consequently, severe outbreaks of the disease. A new generation of viral vector fowl poxvirus (FPV) and herpesvirus of turkey (HVT) vaccines carrying ILTV genes has been developed and such vaccines are commercially available. These vaccines are characterized by their lack of transmission, lack of ILTV-associated latent infections, and no reversion to virulence. HVT-vectored ILTV recombinant vaccines were originally approved for subcutaneous HVT or transcutaneous (pox) delivery. The increased incidence of ILTV outbreaks in broiler production sites encouraged the broiler industry to deliver the FPV-LT and HVT-LT recombinant vaccines in ovo. The objective of this study was to evaluate the protection induced by ILTV viral vector recombinant vaccines after in ovo application in 18-day-old commercial broiler embryos. The protection induced by recombinant ILTV vaccines was assessed by their ability to prevent clinical signs and mortality; to reduce challenge virus replication in the trachea; to prevent an increase in body temperature; and to prevent a decrease in body weight gain after challenge. In this study, both recombinant-vectored ILTV vaccines provided partial protection, thereby mitigating the disease, but did not reduce challenge virus loads in the trachea. PMID:21313847

  10. Effects of patchy ocean fertilization on atmospheric carbon dioxide and biological production

    NASA Astrophysics Data System (ADS)

    Gnanadesikan, Anand; Sarmiento, Jorge L.; Slater, Richard D.

    2003-06-01

    Increasing oceanic productivity by fertilizing nutrient-rich regions with iron has been proposed as a mechanism to offset anthropogenic emissions of carbon dioxide. Earlier studies examined the impact of large-scale fertilization of vast reaches of the ocean for long periods of time. We use an ocean general circulation model to consider more realistic scenarios involving fertilizing small regions (a few hundred kilometers on a side) for limited periods of time (of order 1 month). A century after such a fertilization event, the reduction of atmospheric carbon dioxide is between 2% and 44% of the initial pulse of organic carbon export to the abyssal ocean. The fraction depends on how rapidly the surface nutrient and carbon fields recover from the fertilization event. The modeled recovery is very sensitive to the representation of biological productivity and remineralization. Direct verification of the uptake would be nearly impossible since changes in the air-sea flux due to fertilization would be much smaller than those resulting from natural spatial variability. Because of the sensitivity of the uptake to the long-term fate of the iron and organic matter, indirect verification by measurement of the organic matter flux would require high vertical resolution and long-term monitoring. Finally, the downward displacement of the nutrient profile resulting from an iron-induced productivity spurt may paradoxically lead to a long-term reduction in biological productivity. In the worst-case scenario, removing 1 ton of carbon from the atmosphere for a century is associated with a 30-ton reduction in biological export of carbon.

  11. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    21 Food and Drugs 7 2012-04-01 2012-04-01...68 Section 610.68 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH...or repackaging), distributes, or stores a biological product that is...

  12. Adversomics: a new paradigm for vaccine safety and design.

    PubMed

    Whitaker, Jennifer A; Ovsyannikova, Inna G; Poland, Gregory A

    2015-07-01

    Despite the enormous population benefits of routine vaccination, vaccine adverse events (AEs) and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine acceptance - and thus to infectious disease prevention - worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine AEs, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. The term 'adversomics' was first introduced in 2009 and refers to the study of vaccine adverse reactions using immunogenomics and systems biology approaches. In this review, we present the current state of adversomics research, review known associations and mechanisms of vaccine AEs/reactions, and outline a plan for the further development of this emerging research field. PMID:25937189

  13. Vaccines: countering anthrax: vaccines and immunoglobulins.

    PubMed

    Grabenstein, John D

    2008-01-01

    Anthrax spores rank as the leading threat among bioweapons. This article reviews the accumulated evidence for immunization, either active or passive, to counter the malicious release of anthrax spores. The key protective factor in current anthrax vaccines for humans is a protein called protective antigen, which allows ingress of toxins into cells. The US vaccine is licensed to prevent anthrax, regardless of the route of exposure. Its dosing schedule is cumbersome and somewhat painful (shortcomings that may be resolved by ongoing clinical studies). It can be prescribed with the confidence commensurate with dozens of human safety studies and experience in 1.8 million recent vaccinees. For post-exposure prophylaxis, combining antibiotic prophylaxis and active immunization before illness onset may offer the best combination of prompt and sustained protection, especially for people who inhale large doses of spores. To treat anthrax infection, passive immunization using a polyclonal or monoclonal antibody product may offer important clinical benefit, especially if the anthrax bacteria are resistant to multiple antibiotics. PMID:18171228

  14. Country- and age-specific optimal allocation of dengue vaccines

    PubMed Central

    Mbah, Martial L. Ndeffo; Durham, David P.; Medlock, Jan; Galvani, Alison P.

    2013-01-01

    Several dengue vaccines are under development, and some are expected to become available imminently. Concomitant with the anticipated release of these vaccines, vaccine allocation strategies for dengue endemic countries in Southeast Asia and Latin America are currently under development. We developed a model of dengue transmission that incorporates the age-specific distributions of dengue burden corresponding to those in Thailand and Brazil, respectively, to determine vaccine allocations that minimize the incidence of dengue hemorrhagic fever, taking into account limited availability of vaccine doses in the initial phase of production. We showed that optimal vaccine allocation strategies vary significantly with the demographic burden of dengue hemorrhagic fever. Consequently, the strategy that is optimal for one country may be sub-optimal for another country. More specifically, we showed that, during the first years following introduction of a dengue vaccine, it is optimal to target children for dengue mass vaccination in Thailand, whereas young adults should be targeted in Brazil. PMID:24161462

  15. Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond.

    PubMed

    Yusibov, Vidadi; Streatfield, Stephen J; Kushnir, Natasha

    2011-03-01

    In the last few years, plants have become an increasingly attractive platform for recombinant protein production. This builds on two decades of research, starting with transgenic approaches to develop oral vaccines in which antigens or therapeutics can be delivered in processed plant biomass, and progressing to transient expression approaches whereby high yields of purified targets are administered parenterally. The advantages of plant-based expression systems include high scalability, low upstream costs, biocontainment, lack of human or animal pathogens, and ability to produce target proteins with desired structures and biological functions. Using transgenic and transient expression in whole plants or plant cell culture, a variety of recombinant subunit vaccine candidates, therapeutic proteins, including monoclonal antibodies, and dietary proteins have been produced. Some of these products have been tested in early phase clinical trials, and show safety and efficacy. Among those are mucosal vaccines for diarrheal diseases, hepatitis B and rabies; injectable vaccines for non-Hodgkin's lymphoma, H1N1 and H5N1 strains of influenza A virus, and Newcastle disease in poultry; and topical antibodies for the treatment of dental caries and HIV. As lead plant-based products have entered clinical trials, there has been increased emphasis on manufacturing under current Good Manufacturing Practice (cGMP) guidelines, and the preparation and presentation to the relevant government agencies of regulatory packages. PMID:21346417

  16. Countermeasures and vaccination against terrorism using smallpox: pre-event and post-event smallpox vaccination and its contraindications.

    PubMed

    Sato, Hajime

    2011-09-01

    Smallpox, when used as a biological weapon, presents a serious threat to civilian populations. Core components of the public health management of a terrorism attack using smallpox are: vaccination (ring vaccination and mass vaccination), adverse event monitoring, confirmed and suspected smallpox case management, contact management, identifying, tracing, monitoring contacts, and quarantine. Above all, pre-event and post-event vaccination is an indispensable part of the strategies. Since smallpox patients are most infectious from onset of the rash through the first 7-10 days of the rash, vaccination should be administered promptly within a limited time frame. However, vaccination can accompany complications, such as postvaccinial encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia. Therefore, vaccination is not recommended for certain groups. Public health professionals, as well as physicians and government officials, should also be well equipped with all information necessary for appropriate and effective smallpox management in the face of such a bioterrorism attack. PMID:21431786

  17. Identification and characterization of the constituent human serum antibodies elicited by vaccination

    PubMed Central

    Lavinder, Jason J.; Wine, Yariv; Giesecke, Claudia; Ippolito, Gregory C.; Horton, Andrew P.; Lungu, Oana I.; Hoi, Kam Hon; DeKosky, Brandon J.; Murrin, Ellen M.; Wirth, Megan M.; Ellington, Andrew D.; Dörner, Thomas; Marcotte, Edward M.; Boutz, Daniel R.; Georgiou, George

    2014-01-01

    Most vaccines confer protection via the elicitation of serum antibodies, yet more than 100 y after the discovery of antibodies, the molecular composition of the human serum antibody repertoire to an antigen remains unknown. Using high-resolution liquid chromatography tandem MS proteomic analyses of serum antibodies coupled with next-generation sequencing of the V gene repertoire in peripheral B cells, we have delineated the human serum IgG and B-cell receptor repertoires following tetanus toxoid (TT) booster vaccination. We show that the TT+ serum IgG repertoire comprises ?100 antibody clonotypes, with three clonotypes accounting for >40% of the response. All 13 recombinant IgGs examined bound to vaccine antigen with Kd ? 10?8–10?10 M. Five of 13 IgGs recognized the same linear epitope on TT, occluding the binding site used by the toxin for cell entry, suggesting a possible explanation for the mechanism of protection conferred by the vaccine. Importantly, only a small fraction (<5%) of peripheral blood plasmablast clonotypes (CD3?CD14?CD19+CD27++CD38++CD20?TT+) at the peak of the response (day 7), and an even smaller fraction of memory B cells, were found to encode antibodies that could be detected in the serological memory response 9 mo postvaccination. This suggests that only a small fraction of responding peripheral B cells give rise to the bone marrow long-lived plasma cells responsible for the production of biologically relevant amounts of vaccine-specific antibodies (near or above the Kd). Collectively, our results reveal the nature and dynamics of the serological response to vaccination with direct implications for vaccine design and evaluation. PMID:24469811

  18. Biologically active amines in fermented and non-fermented commercial soybean products from the Spanish market.

    PubMed

    Toro-Funes, N; Bosch-Fuste, J; Latorre-Moratalla, M L; Veciana-Nogués, M T; Vidal-Carou, M C

    2015-04-15

    Biologically active amines were determined in commercial soybean products. The antioxidant polyamines were found in both non-fermented and fermented soybean products. Natto and tempeh showed the highest content of polyamines (75-124 and 11-24 mg/kg of spermidine and spermine, respectively). On the other hand, the bacterial-related biogenic amines, tyramine, histamine, tryptamine and ?-phenylethylamine, were detected in practically all fermented products with a high variability. The highest contents were found in sufu, tamari and soybean paste. Extremely high tyramine and histamine contents, 1700 and 700 mg/kg, respectively, found in some sufu samples could be unhealthy. However, biogenic amines observed in the other soybean products should not be a risk for healthy consumers. However, individuals who take monoamine and diamine oxidase inhibitors drugs should be strongly recommended to avoid this kind of products in order to suffer no adverse health effects. These biogenic amines were not detected in non-fermented soybean products. PMID:25466133

  19. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease

    PubMed Central

    Enjuanes, Luis; DeDiego, Marta L.; Álvarez, Enrique; Deming, Damon; Sheahan, Tim; Baric, Ralph

    2009-01-01

    An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans. PMID:17416434

  20. Dilemmas of a vitalizing vaccine market: lessons from the MMR vaccine/autism debate.

    PubMed

    Bragesjö, Fredrik; Hallberg, Margareta

    2011-03-01

    A number of issues related to vaccines and vaccinations in society are discussed in this paper. Our purpose is to merge an analysis of some recent changes in the vaccine market with social science research on the relationship between citizens and authorities. The article has two empirical parts. The first shows how the vaccine market, which for many years has had immense financial problems, nowadays seems to becoming economically vitalized, mostly due to the production of new and profitable vaccines. However prosperous the future may appear, certain reactions from the public regarding vaccination initiatives offer insight into inherent problems of vaccine policies in many Western countries. In the second part of the article, these problems are exemplified with the recent controversy over the MMR (measles, mumps, and rubella) vaccine. We conclude that in spite of the improving profit-margins, the vaccine market remains vulnerable and insecure. Vaccines are permeated by society, even more so than pharmaceutics that are used to cure or alleviate illnesses. Radical changes in financial conditions with promises of a more profitable market will not, we argue, solve other even more fundamental problems. PMID:21560548

  1. Production of avirulent mutants of Mycobacterium bovis with vaccine properties by the use of illegitimate recombination and screening of stationary-phase cultures

    Microsoft Academic Search

    D. M. Collins; T. Wilson; S. Campbell; B. M. Buddle; B. J. Wards; G. Hotter; G. W. de Lisle

    A better tuberculosis vaccine is urgently required to control the continuing epidemic. Molecular techniques are now available to produce a better live vaccine than BCG by producing avirulent strains of the Mycobacterium tuberculosis complex with known gene deletions. In this study, 1000 illegitimate recombinants of Mycobacterium bovis were produced by illegitimate recombination with fragments of mycobacterial DNA containing a kanamycin

  2. Vaccines today, vaccines tomorrow: a perspective.

    PubMed

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  3. Vaccines today, vaccines tomorrow: a perspective

    PubMed Central

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  4. Biological hydrogen sulfide production in an ethanol–lactate fed fluidized-bed bioreactor

    Microsoft Academic Search

    Laura M. Nevatalo; Annukka E. Mäkinen; Anna H. Kaksonen; Jaakko A. Puhakka

    2010-01-01

    Sulfate-reducing fluidized-bed bioreactor (FBR) fed with ethanol–lactate mixture was operated at 35°C for 540days to assess mine wastewater treatment, biological hydrogen sulfide production capacity and acetate oxidation kinetics. During the mine wastewater treatment period with synthetic wastewater, the sulfate reduction rate was 62mmol SO42-L?1d?1 and Fe and Zn precipitation rates were 11mmol FeL?1d?1 and 1mmol ZnL?1d?1. After this, the hydrogen

  5. Vaccines for immunological control of fertility

    Microsoft Academic Search

    Satish K. Gupta; Pankaj Bansal

    2010-01-01

    Vaccines have been proposed as one of the strategies for population control. Immunocontraceptive vaccines can be designed\\u000a to inhibit: (1) production of gametes (sperm and egg); (2) functions of gametes, leading to blocking of fertilization; and\\u000a (3) gamete outcome (pregnancy). Immunization with gonadotropin-releasing hormone coupled to different carriers has shown curtailment\\u000a in the production of sperm with concomitant infertility in

  6. Human papillomavirus vaccine update.

    PubMed

    Gilmer, Lisa S

    2015-03-01

    This article provides an overview of human papillomavirus (HPV) infection and the burden of HPV-related diseases, including cervical cancer, in the United States. The article presents an overview of HPV vaccination, including the efficacy and safety of the HPV vaccine, recommendations for vaccination in the adolescent population, as well as points to counter several of the common barriers to vaccination. This information is valuable to providers in their efforts to consistently and strongly recommend HPV vaccination. PMID:25634702

  7. Existing antiviral vaccines.

    PubMed

    Ravanfar, Parisa; Satyaprakash, Anita; Creed, Rosella; Mendoza, Natalia

    2009-01-01

    The innovation of vaccines has allowed for one of the greatest advancements in the history of public health. The first of the vaccines have been the antiviral vaccines, in particular the smallpox vaccine that was first developed by Edward Jenner in 1796. This article will review vaccination for the following viral diseases: measles, mumps, rubella, polio, hepatitis A, hepatitis B, influenza, rotavirus, rabies, monkeypox, smallpox, Japanese encephalitis, and yellow fever. PMID:19335723

  8. University contributions to the HPV vaccine and implications for access to vaccines in developing countries: addressing materials and know-how in university technology transfer policy.

    PubMed

    Crager, Sara E; Guillen, Ethan; Price, Matt

    2009-01-01

    Human Papillomavirus (HPV) is a major cause of morbidity and mortality worldwide, with most of the disease burden concentrated in developing countries. Over 90 percent of cervical cancer deaths, almost all of which are caused by HPV, occur in low- and middle-income countries where access to goods and services for prevention and treatment pose major barriers to intervention. In resource-poor settings lacking the capacity for routine screening for cervical cancer, the HPV vaccines developed by Merck and GlaxoSmithKline are desperately needed to help prevent these unnecessary deaths. The initial development of currently available HPV vaccines took place at a number of universities and other publicly funded institutions, yet there is little low-cost access to the vaccine in developing countries where access would be most critical. This is the rule rather than the exception with most university-discovered medicines. Universities and other publicly-funded institutions can adopt a number of licensing methods to ensure that vaccines discovered on their campuses are available at low-cost in developing countries. Universities Allied for Essential Medicines has proposed that universities adopt Global Access Licensing policies to implement these changes by enabling generic or low-cost production of the end product in developing countries. Generic competition is a critical market force that has, for instance, driven down the price of HIV/AIDS treatments from more than $10,000 to less than $99 per patient per year today. While the central barrier to creation of small molecule generics is patent-protection, there are multiple additional barriers that need to be addressed in order to ensure the efficient production of cost-effective generic vaccines and other biologics. While certain biologics may require generic producers to perform additional clinical trials, vaccines are in a somewhat unique situation with respect to both safety and efficacy. With access to appropriate patents, materials and knowledge, vaccines have the potential to be evaluated efficiently and cost-effectively via a pathway parallel to establishing bioequivalence for generic small molecule drugs. A new paradigm is needed that addresses the additional barriers that exist, outside of simply patent protection, to the generic production of vaccines and other biologics. One possible framework, which builds upon previous work on prize funds and patent pools, is discussed here: a Patents, Materials, and Know-how Pool (PMK Pool), based on the patent pool model such as those outlined in the Essential Medical Inventions Licensing Agency and proposals recently put forth by the governments of Barbados and Bolivia. University approaches to licensing vaccines and other biologics need to ensure access not only to patents, knowledge, and materials covered by intellectual property, but must also address the problem of access to materials and know-how that are often proprietary trade secrets. Universities should actively participate in the creation of this and other novel mechanisms, and in the meantime use currently available technology transfer mechanisms to ensure low-cost access to medicines in developing countries. PMID:19697749

  9. Maintaining the cold chain for vaccines.

    PubMed

    Petrovi?, Vladimir; Seguljev, Zorica; Gajin, Branka

    2005-01-01

    Cold chain for vaccines a is a system for storing and transporting vaccines at very low temperatures to maintain their effectiveness before use. Because vaccines are sensitive biological substances, their exposition to high temperatures directly affects the quality of vaccines and safety of immunization. The goal of this study was to assess the safety of cold chain for vaccines within the cold chain system in two services of Health Center Novi Sad. Cold Chain Monitors (CCM) and Freeze Watch (FW) indicators were used. A total of 155 (94.5%) Cold Chain Monitors (CCM) and 100 (95.2%) Freeze Watch (FW) indicators were analyzed. Only one CCM showed a breack in cold chain. A total of 3 CCMs indicated risk of vaccine wastage. A total of 9 CCMs were colorized without risk of vaccine wastage. FWs were positive in a high percentage in both services of Health Center Novi Sad. FWs were exposed to low temperatures during transport. Statistically significant differencies in the number of exposed CCMs to high temperatures and the number of exposed FWs to low temperatures were observed in these two services. A statistically significant difference in number of FWs exposed to low temperatures was observed in regard to the period of transport and the period of storage at the vaccination stations. The study shows high level of safety of the cold chain in two services of Health Center Novi Sad Cold Chain Monitor is a reliable indicator of the quality of cold chain for vaccines. Freeze Watch is a reliable indicator of the quality of cold chain during storage of vaccines, but not during their transport. PMID:16296574

  10. “All manner of ills”: The features of serious diseases attributed to vaccination

    Microsoft Academic Search

    Julie Leask; Simon Chapman; Spring Chenoa Cooper Robbins

    2010-01-01

    Anti-vaccination writings have linked vaccines with a wide range of negative outcomes. The majority of evidence negates such connections raising the question of what makes these attributions attractive. This research identified diseases and conditions which are claimed to have been caused by vaccines and identified their shared societal features. They shared an idiopathic origin; apparent rise in incidence; face-value biological

  11. Immune responses of bison and efficacy after booster vaccination with Brucella abortus strain RB51.

    PubMed

    Olsen, S C; McGill, J L; Sacco, R E; Hennager, S G

    2015-04-01

    Thirty-one bison heifers were randomly assigned to receive saline or a single vaccination with 10(10) CFU of Brucella abortus strain RB51. Some vaccinated bison were randomly selected for booster vaccination with RB51 at 11 months after the initial vaccination. Mean antibody responses to RB51 were greater (P < 0.05) in vaccinated bison after initial and booster vaccination than in nonvaccinated bison. The proliferative responses by peripheral blood mononuclear cells (PBMC) from the vaccinated bison were greater (P < 0.05) than those in the nonvaccinated bison at 16 and 24 weeks after the initial vaccination but not after the booster vaccination. The relative gene expression of gamma interferon (IFN-?) was increased (P < 0.05) in the RB51-vaccinated bison at 8, 16, and 24 weeks after the initial vaccination and at 8 weeks after the booster vaccination. The vaccinated bison had greater (P < 0.05) in vitro production of IFN-? at all sampling times, greater interleukin-1? (IL-1?) production in various samplings after the initial and booster vaccinations, and greater IL-6 production at one sampling time after the booster vaccination. Between 170 and 180 days of gestation, the bison were intraconjunctivally challenged with approximately 1 × 10(7) CFU of B. abortus strain 2308. The incidences of abortion and infection were greater (P < 0.05) in the nonvaccinated bison after experimental challenge than in the bison receiving either vaccination treatment. Booster-vaccinated, but not single-vaccinated bison, had a reduced (P < 0.05) incidence of infection in fetal tissues and maternal tissues compared to that in the controls. Compared to the nonvaccinated bison, both vaccination treatments lowered the colonization (measured as the CFU/g of tissue) of Brucella organisms in all tissues, except in retropharyngeal and supramammary lymph nodes. Our study suggests that RB51 booster vaccination is an effective vaccination strategy for enhancing herd immunity against brucellosis in bison. PMID:25673305

  12. Strategies for cancer therapy using carcinoembryonic antigen vaccines

    Microsoft Academic Search

    Howard L. Kaufman; Heidi Hörig; Freddy A. Medina; Sue Golding; William A. Conkright

    2000-01-01

    Advances in molecular biology and immunology have renewed interest in the development of vaccines for the treatment or prevention of cancer. Research over the past 10 years has focused on the identification of suitable tumour antigens to use as targets for a variety of vaccine strategies. Carcinoembryonic antigen (CEA) was one of the first tumour antigens described, and is commonly

  13. Viruses as vaccine vectors for infectious diseases and cancer

    Microsoft Academic Search

    Jonathan L. Heeney; Simon J. Draper

    2009-01-01

    Recent developments in the use of viruses as vaccine vectors have been facilitated by a better understanding of viral biology. Advances occur as we gain greater insight into the interrelationship of viruses and the immune system. Viral-vector vaccines remain the best means to induce cellular immunity and are now showing promise for the induction of strong humoral responses. The potential

  14. Anthrax vaccine: short-term safety experience in humans

    Microsoft Academic Search

    Phillip R Pittman; Paul H Gibbs; Timothy L Cannon; Arthur M Friedlander

    2001-01-01

    Bacillus anthracis is the major terrorist and biological warfare agent of concern to civilian and military medical planners. The licensed anthrax vaccine, adsorbed (AVA) is believed to be an effective prophylactic medical countermeasure against this threat. Our objective in this report was to expand the safety database for this vaccine by assessing data on self-reported, short-term safety of AVA during

  15. MODIFIED LIVE VACCINES FOR GRAM NEGATIVE PATHOGENS OF CATFISH

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines, adjuvants and immunostimulants encompass a variety of biological compounds capable of producing immune responses against aquatic animal pathogens. The prevention of diseases is becoming more dependent on the use of immunobiologics in aquatic animals, especially vaccines in fish. An impor...

  16. Model format for a vaccine stability report and software solutions

    Microsoft Academic Search

    Jinho Shin; Timothy Schofield

    2009-01-01

    A session of the International Association for Biologicals Workshop on Stability Evaluation of Vaccine, a Life Cycle Approach was devoted to a model format for a vaccine stability report, and software solutions. Presentations highlighted the utility of a model format that will conform to regulatory requirements and the ICH common technical document. However, there need be flexibility to accommodate individual

  17. Macrofaunal production and biological traits: Spatial relationships along the UK continental shelf

    NASA Astrophysics Data System (ADS)

    Bolam, S. G.; Eggleton, J. D.

    2014-04-01

    Biological trait analysis (BTA) is increasingly being employed to improve our understanding of the ecological functioning of marine benthic invertebrate communities. However, changes in trait composition are seldomly compared with concomitant changes in metrics of ecological function. Consequently, inferences regarding the functional implications of any changes are often anecdotal; we currently have a limited understanding of the functional significance of the traits commonly used. In this study, we quantify the relationship between benthic invertebrate trait composition and secondary production estimates using data spanning almost the breadth of the UK continental shelf. Communities described by their composition of 10 traits representing life history, morphology and behaviour showed strong relationships with variations in total secondary production. A much weaker relationship was observed for community productivity (or P:B), a measure of rate of energy turnover. Furthermore, the relationship between total production and multivariate taxonomic community composition was far weaker than that for trait composition. Indeed, the similarities between communities as defined by taxonomy were very different from those depicted by their trait composition. That is, as many studies have demonstrated, taxonomically different communities may display similar trait compositions, and vice versa. Finally, we found that descriptions of community trait composition vary greatly depending on whether abundance or biomass is used as the enumeration weighting method during BTA, and trait assessments based on biomass produced better relations with secondary production than those based on abundance. We discuss the significance of these findings with respect to BTA using marine benthic invertebrates.

  18. Large animal models for vaccine development and testing.

    PubMed

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-05-19

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. PMID:25991698

  19. Vaccinations in juvenile chronic inflammatory diseases: an update.

    PubMed

    Silva, Clovis A; Aikawa, Nadia E; Bonfa, Eloisa

    2013-09-01

    Vaccination is a powerful tool to reduce the burden of infectious diseases in paediatric patients with chronic rheumatic diseases. Live attenuated vaccines are not recommended for profoundly immunosuppressed patients, but nonlive vaccines have adequate safety and efficacy profiles in the few (admittedly underpowered) studies published to date. No severe vaccine-specific or disease-specific adverse events have been observed in patients with juvenile idiopathic arthritis (JIA) or childhood-onset systemic lupus erythematosus (SLE) who have been vaccinated with live or nonlive agents. The immune response to live vaccines is variable in these patients but generally adequate, despite concomitant use of immunosuppressive and biologic agents. The proposal that onset of autoimmune rheumatic diseases could be induced by vaccination is controversial and primarily based on case reports; however, patients with mevalonate kinase deficiency can experience febrile attacks after immunizations. Adequately powered studies of live and nonlive vaccination in patients with paediatric rheumatic diseases are necessary to clarify safety and efficacy issues. This narrative Review discusses vaccination in patients with JIA, childhood-onset SLE, juvenile dermatomyositis, juvenile systemic sclerosis, primary vasculitis and autoinflammatory syndromes. Vaccine safety, short-term and long-term changes in disease parameters, and the immunogenicity and influence of immunosuppressive agents are outlined for each combination of disease and vaccine. PMID:23820860

  20. An experimental rabies vaccine produced with a new BHK-21 suspension cell culture process: use of serum-free medium and perfusion-reactor system

    Microsoft Academic Search

    Pierre Perrin; Shampur Madhusudana; Corinne Gontier-Jallet; Stephane Petres; Noël Tordo; Otto-Wilhelm Merten

    1995-01-01

    An experimental rabies vaccine was prepared from the BHK-21 cell line adapted to culture in suspension using bioreactors. A new serum-free medium (MDSS2) (Merten et al., Cytotechnology, 1994, 14, 47) developed for the culture of various cell lines and for the production of several biologicals, was used for cell culture and virus production. The PV-Paris\\/BHK-21 rabies virus strain (adapted to

  1. Annual net community production and the biological carbon flux in the ocean

    NASA Astrophysics Data System (ADS)

    Emerson, Steven

    2014-01-01

    The flux of biologically produced organic matter from the surface ocean (the biological pump), over an annual cycle, is equal to the annual net community production (ANCP). Experimental determinations of ANCP at ocean time series sites using a variety of different metabolite mass balances have made it possible to evaluate the accuracy of sediment trap fluxes and satellite-determined ocean carbon export. ANCP values at the Hawaii Ocean Time-series (HOT), the Bermuda Atlantic Time-series Study (BATS), Ocean Station Papa (OSP) are 3 ± 1 mol C m-2 yr-1—much less variable than presently suggested by satellite remote sensing measurements and global circulation models. ANCP determined from mass balances at these locations are 3-4 times particulate organic carbon fluxes measured in sediment traps. When the roles of dissolved organic carbon (DOC) flux, zooplankton migration, and depth-dependent respiration are considered these differences are reconciled at HOT and OSP but not at BATS, where measured particulate fluxes are about 3 times lower than expected. Even in the cases where sediment trap fluxes are accurate, it is not possible to "scale up" these measurements to determine ANCP without independent determinations of geographically variable DOC flux and zooplankton migration. Estimates of ANCP from satellite remote sensing using net primary production determined by the carbon-based productivity model suggests less geographic variability than its predecessor (the vertically generalized productivity model) and brings predictions at HOT and OSP closer to measurements; however, satellite-predicted ANCP at BATS is still 3 times too low.

  2. Salmonella-based plague vaccines for bioterrorism.

    PubMed

    Calhoun, Leona Nicole; Kwon, Young-Min

    2006-04-01

    Yersinia pestis, the causative agent of plague, is an emerging threat as a means of bioterrorism. Accordingly, the Working Group on Civilian Biodefense, as well as the Centers for Disease Control and Prevention, has specified Y. pestis as a prime candidate for use in bioterrorism. As the threat of bioterrorism increases, so does the need for an effective vaccine against this potential agent. Experts agree that a stable, non-invasive vaccine would be necessary for the rapid large-scale immunization of a population following a bioterrorism attack. Thus far, live Salmonella-based oral vaccines show the most potential for this purpose. When delivered via a mucosal route, Salmonella-based plague vaccines show the ability to protect against the deadly pneumonic form of plague. Also, mass production, distribution, and administration are easier and less costly for attenuated Salmonella-based plague vaccines than for plague vaccines consisting of purified proteins. Most attenuated Salmonella-based plague vaccines have utilized a plasmid-based expression system to deliver plague antigen(s) to the mucosa. However, these systems are frequently associated with plasmid instability, an increased metabolic burden upon the vaccine strain, and highly undesirable antibiotic resistance genes. The future of Salmonella-based plague vaccines seems to lie in the use of chromosomally encoded plague antigens and the use of in vivo inducible promoters to drive their expression. This method of vaccine development has been proven to greatly increase the retention of foreign genes, and also eliminates the need for antibiotic resistance genes within Salmonella-based vaccines. PMID:16604240

  3. Evaluation of biological safety in vitro and immunogenicity in vivo of recombinant Escherichia coli Shiga toxoids as candidate vaccines in cattle.

    PubMed

    Kerner, Katharina; Bridger, Philip S; Köpf, Gabriele; Fröhlich, Julia; Barth, Stefanie; Willems, Hermann; Bauerfeind, Rolf; Baljer, Georg; Menge, Christian

    2015-01-01

    Cattle are the most important reservoir for enterohemorrhagic Escherichia coli (EHEC), a subset of shigatoxigenic E. coli (STEC) capable of causing life-threatening infectious diseases in humans. In cattle, Shiga toxins (Stx) suppress the immune system thereby promoting long-term STEC shedding. First infections of animals at calves' age coincide with the lack of Stx-specific antibodies. We hypothesize that vaccination of calves against Shiga toxins prior to STEC infection may help to prevent the establishment of a persistent type of infection. The objectives of this study were to generate recombinant Shiga toxoids (rStx1mut & rStx2mut) by site-directed mutagenesis and to assess their immunomodulatory, antigenic, and immunogenic properties. Cultures of bovine primary immune cells were used as test systems. In ileal intraepithelial lymphocytes both, recombinant wild type Stx1 (rStx1WT) and rStx2WT significantly induced transcription of IL-4 mRNA. rStx1WT and rStx2WT reduced the expression of Stx-receptor CD77 (syn. Globotriaosylceramide, Gb3) on B and T cells from peripheral blood and of CD14 on monocyte-derived macrophages. At the same concentrations, rStx1mut and rStx2mut exhibited neither of these effects. Antibodies in sera of cattle naturally infected with STEC recognized the rStxmut toxoids equally well as the recombinant wild type toxins. Immunization of calves with rStx1mut plus rStx2mut led to induction of antibodies neutralizing Stx1 and Stx2. While keeping their antigenicity and immunogenicity recombinant Shiga toxoids are devoid of the immunosuppressive properties of the corresponding wild type toxins in cattle and candidate vaccines to mitigate long-term STEC shedding by the reservoir host. PMID:25889651

  4. EFFECTS OF BIOLOGICALLY DERIVED PRODUCTS ON MOBILITY AND REPRODUCTION OF THE ROOT LESION NEMATODE, PRATYLENCHUS PENETRANS, ON STRAWBERRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biological products reported to have nematotoxic effects were evaluated for the suppression of P. penetrans mobility in vitro and reproduction on strawberry plants. Mobility was evaluated by exposing nematodes to a range of concentrations of products in aqueous solutions for 24, 48, and 72 h, follo...

  5. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

    PubMed

    Pichichero, Michael E

    2013-12-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  6. HIV Infection and Adult Vaccination

    MedlinePLUS

    ... to protect against pneumonia and other pneumococcal diseases Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ... to protect against pneumonia and other pneumococcal diseases Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ...

  7. Vaccines, Reverse Vaccinology, and Bacterial Pathogenesis

    PubMed Central

    Delany, Isabel; Seib, Kate L.

    2013-01-01

    Advances in genomics and innovative strategies such as reverse vaccinology have changed the concepts and approaches to vaccine candidate selection and design. Genome mining and blind selection of novel antigens provide a novel route to investigate the mechanisms that underpin pathogenesis. The resulting lists of novel candidates are revealing new aspects of pathogenesis of target organisms, which in turn drives the rational design of optimal vaccine antigens. Here we use the discovery, characterization, and exploitation of fHbp, a vaccine candidate and key virulence factor of meningococcus, as an illustrative case in point. Applying genomic approaches to study both the pathogen and host will ultimately increase our fundamental understanding of pathogen biology, mechanisms responsible for the development of protective immunity, and guide next-generation vaccine design. PMID:23637311

  8. Periodontal vaccine: A dream or reality.

    PubMed

    Kudyar, Nitin; Dani, Nitin; Mahale, Swapna

    2011-04-01

    Recent advances in cellular and molecular biology have led to the development of new strategies for vaccines against many types of infectious diseases. It has long been recognized that individuals who recovered from a disease developed subsequent resistance to the same. In the late 18th century, Edward Jenner developed and established the principle of vaccination using the cross protection conferred by cowpox virus, which is non-pathogenic in humans. With the rapid growth of microbial genome sequencing and bioinformatics analysis tools we have the potential to examine all the genes and proteins from any human pathogen. This technique has the capability to provide us with new targets for anti-microbial drugs and vaccines. However, to realize this potential new bioinformatics and experimental approaches to select these targets from the myriad of available candidates are required. Vaccination is a process that induces specific immune resistance to a bacterial or viral infection. PMID:21976833

  9. Clinical Applications of DNA Vaccines: Current Progress

    PubMed Central

    Ferraro, Bernadette; Morrow, Matthew P.; Hutnick, Natalie A.; Shin, Thomas H.; Lucke, Colleen E.

    2011-01-01

    It was discovered almost 20 years ago that plasmid DNA, when injected into the skin or muscle of mice, could induce immune responses to encoded antigens. Since that time, there has since been much progress in understanding the basic biology behind this deceptively simple vaccine platform and much technological advancement to enhance immune potency. Among these advancements are improved formulations and improved physical methods of delivery, which increase the uptake of vaccine plasmids by cells; optimization of vaccine vectors and encoded antigens; and the development of novel formulations and adjuvants to augment and direct the host immune response. The ability of the current, or second-generation, DNA vaccines to induce more-potent cellular and humoral responses opens up this platform to be examined in both preventative and therapeutic arenas. This review focuses on these advances and discusses both preventive and immunotherapeutic clinical applications. PMID:21765081

  10. The great 2012 Arctic Ocean summer cyclone enhanced biological productivity on the shelves

    PubMed Central

    Zhang, Jinlun; Ashjian, Carin; Campbell, Robert; Hill, Victoria; Spitz, Yvette H; Steele, Michael

    2014-01-01

    [1] A coupled biophysical model is used to examine the impact of the great Arctic cyclone of early August 2012 on the marine planktonic ecosystem in the Pacific sector of the Arctic Ocean (PSA). Model results indicate that the cyclone influences the marine planktonic ecosystem by enhancing productivity on the shelves of the Chukchi, East Siberian, and Laptev seas during the storm. Although the cyclone's passage in the PSA lasted only a few days, the simulated biological effects on the shelves last 1 month or longer. At some locations on the shelves, primary productivity (PP) increases by up to 90% and phytoplankton biomass by up to 40% in the wake of the cyclone. The increase in zooplankton biomass is up to 18% on 31 August and remains 10% on 15 September, more than 1 month after the storm. In the central PSA, however, model simulations indicate a decrease in PP and plankton biomass. The biological gain on the shelves and loss in the central PSA are linked to two factors. (1) The cyclone enhances mixing in the upper ocean, which increases nutrient availability in the surface waters of the shelves; enhanced mixing in the central PSA does not increase productivity because nutrients there are mostly depleted through summer draw down by the time of the cyclone's passage. (2) The cyclone also induces divergence, resulting from the cyclone's low-pressure system that drives cyclonic sea ice and upper ocean circulation, which transports more plankton biomass onto the shelves from the central PSA. The simulated biological gain on the shelves is greater than the loss in the central PSA, and therefore, the production on average over the entire PSA is increased by the cyclone. Because the gain on the shelves is offset by the loss in the central PSA, the average increase over the entire PSA is moderate and lasts only about 10 days. The generally positive impact of cyclones on the marine ecosystem in the Arctic, particularly on the shelves, is likely to grow with increasing summer cyclone activity if the Arctic continues to warm and the ice cover continues to shrink.

  11. DNA vaccines against anthrax.

    PubMed

    Galloway, Darrell R; Baillie, Les

    2004-10-01

    DNA vaccination is vaccination at its simplest. Due to renewed interest in vaccination against anthrax and other biothreat agents, a genetic immunisation approach offers attractive possibilities for rapid, responsive vaccine development. DNA vaccination against anthrax is an active area of research showing promising results at present, which in the short-term and in the future could form the basis for new advances in multi-agent vaccine development. The anthrax 'model' constitutes an important experimental system for genetic immunisation technology development. PMID:15461577

  12. Determination of production biology of cladocera in a reservoir receiving hyperthermal effluents from a nuclear production reactor. [Par Pond

    SciTech Connect

    Vigerstad, T J

    1980-01-01

    The effects on zooplankton of residence in a cooling reservoir receiving hyperthermal effluents directly from a nuclear-production-reactor were studied. Rates of cladoceran population production were compared at two stations in the winter and summer of 1976 on Par Pond located on the Savannah River Plant, Aiken, SC. One station was located in an area of the reservoir directly receiving hyperthermal effluent (Station MAS) and the second was located about 4 km away in an area where surface temperatures were normal for reservoirs in the general geographical region (Station CAS). A non-parametric comparison between stations of standing stock and fecundity data for Bosmina longirostris, taken for the egg ratio model, was used to observe potential hyperthermal effluent effects. There was a statistically higher incidence of deformed eggs in the Bosmina population at Station MAS in the summer. Bosmina standing stock underwent two large oscillations in the winter and three large oscillations in the summer at Station MAS compared with two in the winter and one in the summer at Station CAS. These results are consistent with almost all other Par Pond studies which have found the two stations to be essentially similar in spectra composition but with some statistically significant differences in various aspects of the biology of the species.

  13. Side effects of plant protection products and biological interactions on the European earwig Forficula auricularia L.

    PubMed

    Peusens, G; Moerkens, R; Beliën, T; Gobin, B

    2009-01-01

    Plant protection products are designed to control pests but can have negative side effects on non-target arthropods thus disturbing the important population of natural enemies required for biological control. Although the European earwig, Forficula auricularia L, (Dermaptera: Forficulidae) is not considered to be a key beneficial in pome fruit, it is an important predator of several pests, e.g. woolly apple aphid and pear sucker. The impact of non-selective plant protection products at crucial moments in their (univoltine) life cycle can be of significant relevance compared to insects with numerous generations. Foliar applications in spring when nymphs are migrating into the trees can reduce the number of adults in summer and subsequently affect the population size next year. Multiple and/or combined spraying during summer on adults may have a cumulative effect resulting in less over wintering females which possibly exhibit poor reproductive performance. Previous residual contact bioassays already revealed the harmful side effect of several formulated products on adults. Insects showing sub lethal symptoms recovered partially or died eventually. As spinosad caused significant toxicological effects it was subsequently tested in 3 different dose rates on adults and N4-nymphs. We noticed not only a clear dose-response relationship but N4-nymphs proved to be more susceptible than adults; even a dilution of 1/9-th of the registered dose rate still caused a mortality of 45.5 % after 20 days. Understanding the earwig's population dynamics is essential for efficient practical biocontrol. It proves difficult to increase population levels to sufficient high numbers for optimal pest control. Local biological factors might be limiting. Therefore, we tested two hypotheses that pertain to population limitation: 1. Bird predation during summer, 2. Small mammal nest predation during winter. Enclosure experiments showed no negative bird effect on earwig densities unless large bird flocks inhabited the area. Small mammals did not actively predate the over wintering nests, although other predatory arthropods may be important. PMID:20222599

  14. An Assessment of biological Potency and Molecular Characteristics of Different Innovator and Noninnovator Interferon-Beta Products

    Microsoft Academic Search

    A. Maeger; C. Dolman; P. Dilger; C. Bird; G. Giovannoni; H. Schellekens; R. Thorpe; M. Wadhwa

    2011-01-01

    Approved innovator products and their noninnovator ‘‘copy’’ versions are likely to vary in their quality, eg,\\u000aphysicochemical characteristics and biological activity, with important implications for clinical efficacy and\\u000asafety. Therefore, it is important to study and thoroughly evaluate the noninnovator products in comparison\\u000awith approved products at the preclinical and clinical stages. We have obtained 4 noninnovator interferon (IFN)-\\u000ab-1a

  15. 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

  16. Developing Countries Vaccine Manufacturers Network: doing good by making high-quality vaccines affordable for all.

    PubMed

    Pagliusi, Sonia; Leite, Luciana C C; Datla, Mahima; Makhoana, Morena; Gao, Yongzhong; Suhardono, Mahendra; Jadhav, Suresh; Harshavardhan, Gutla V J A; Homma, Akira

    2013-04-18

    The Developing Countries Vaccine Manufacturers Network (DCVMN) is a unique model of a public and private international alliance. It assembles governmental and private organizations to work toward a common goal of manufacturing and supplying high-quality vaccines at affordable prices to protect people around the world from known and emerging infectious diseases. Together, this group of manufacturers has decades of experience in manufacturing vaccines, with technologies, know-how, and capacity to produce more than 40 vaccines types. These manufacturers have already contributed more than 30 vaccines in various presentations that have been prequalified by the World Health Organization for use by global immunization programmes. Furthermore, more than 45 vaccines are in the pipeline. Recent areas of focus include vaccines to protect against rotavirus, human papillomavirus (HPV), Japanese encephalitis, meningitis, hepatitis E, poliovirus, influenza, and pertussis, as well as combined pentavalent vaccines for children. The network has a growing number of manufacturers that produce a growing number of products to supply the growing demand for vaccines in developing countries. PMID:23598479

  17. High throughput screening of particle conditioning operations: II. Evaluation of scale-up heuristics with prokaryotically expressed polysaccharide vaccines.

    PubMed

    Noyes, Aaron; Huffman, Ben; Berrill, Alex; Merchant, Nick; Godavarti, Ranga; Titchener-Hooker, Nigel; Coffman, Jonathan; Sunasara, Khurram; Mukhopadhyay, Tarit

    2015-08-01

    Multivalent polysaccharide conjugate vaccines are typically comprised of several different polysaccharides produced with distinct and complex production processes. Particle conditioning steps, such as precipitation and flocculation, may be used to aid the recovery and purification of such microbial vaccine products. An ultra scale-down approach to purify vaccine polysaccharides at the micro-scale would greatly enhance productivity, robustness, and speed the development of novel conjugate vaccines. In part one of this series, we described a modular and high throughput approach to develop particle conditioning processes (HTPC) for biologicals that combines flocculation, solids removal, and streamlined analytics. In this second part of the series, we applied HTPC to industrially relevant feedstreams comprised of capsular polysaccharides (CPS) from several bacterial species. The scalability of HTPC was evaluated between 0.8?mL and 13?L scales, with several different scaling methodologies examined. Clarification, polysaccharide yield, impurity clearance, and product quality achieved with HTPC were reproducible and comparable with larger scales. Particle sizing was the response with greatest sensitivity to differences in processing scale and enabled the identification of useful scaling rules. Scaling with constant impeller tip speed or power per volume in the impeller swept zone offered the most accurate scale up, with evidence that time integration of these values provided the optimal basis for scaling. The capability to develop a process at the micro-scale combined with evidence-based scaling metrics provide a significant advance for purification process development of vaccine processes. The USD system offers similar opportunities for HTPC of proteins and other complex biological molecules. Biotechnol. Bioeng. 2015;112: 1568-1582. © 2015 Wiley Periodicals, Inc. PMID:25727194

  18. [Smallpox vaccine, then and now. From the "cow lymphe" to the cell-culture vaccine].

    PubMed

    Hochstein-Mintzel, V

    1977-01-13

    There have been few changes in the preparation of smallpox vaccine since Eduard Jenner described his method of preventive inoculation in 1798. Jenner's vaccine, "the matter", was maintained in man by arm to arm passage. The only major achievement in production methods was the introduction of an animal host for virus propagation. The skin of living calves or sheep was inoculated with seed virus and the "pulp" harvested three to four days later. The disadvantages of this procedure are evident: massive bacterial contamination in spite of rigorous cleanliness and excessive amounts of undesired tissue debris in the crude material to be used for vaccine production. In spite of these obvious disadvantages the method is still in use all over the world. Advances in tissue culture techniques have led to the production of all modern vaccines for use in animals and in the human from this substrate with low initial content of foreign protein and of primary sterility. The only exception today is conventional smallpox vaccine. Sporadic attempts to produce smallpox vaccine in tissue culture have been recently and successfully made in England, Holland and Yugoslavia. The Bavarian State Institute of Vaccination has adopted Vaccinia strain Elstree to primary cultures of chick embryo fibroblasts. The virus propagation in roller bottles permits the economical production of a high titered vaccine with a stability equal to that of calf origin. The cell culture harvest is bacteriologically steril and has a minimal content of foreign protein. Within the past two years this cell culture vaccine has totally replaced the old "calf lymph". Vaccination takes are equal, complications have so far not come to our attention. PMID:13033

  19. Biological Production of Methane from Lunar Mission Solid Waste: An Initial Feasibility Assessment

    NASA Astrophysics Data System (ADS)

    Strayer, Richard; Garland, Jay; Janine, Captain

    A preliminary assessment was made of the potential for biological production of methane from solid waste generated during an early planetary base mission to the moon. This analysis includes: 1) estimation of the amount of biodegradable solid waste generated, 2) background on the potential biodegradability of plastics given their significance in solid wastes, and 3) calculation of potential methane production from the estimate of biodegradable waste. The completed analysis will also include the feasibility of biological methane production costs associated with the biological processing of the solid waste. NASA workshops and Advanced Life Support documentation have estimated the projected amount of solid wastes generated for specific space missions. From one workshop, waste estimates were made for a 180 day transit mission to Mars. The amount of plastic packaging material was not specified, but our visual examination of trash returned from stocktickerSTS missions indicated a large percentage would be plastic film. This plastic, which is not biodegradable, would amount to 1.526 kgdw crew-1 d-1 or 6.10 kgdw d-1 for a crew of 4. Over a mission of 10 days this would amount to 61 kgdw of plastics and for an 180 day lunar surface habitation it would be nearly 1100 kgdw . Approx. 24 % of this waste estimate would be biodegradable (human fecal waste, food waste, and paper), but if plastic packaging was replaced with biodegradable plastic, then 91% would be biodegradable. Plastics are man-made long chain polymeric molecules, and can be divided into two main groups; thermoplastics and thermoset plastics. Thermoplastics comprise over 90% of total plastic use in the placecountry-regionUnited States and are derived from polymerization of olefins via breakage of the double bond and subsequent formation of additional carbon to carbon bonds. The resulting sole-carbon chain polymers are highly resistant to biodegradation and hydrolytic cleavage. Common thermoplastics include low density polyethylene (packaging, bags), high density polyethylene (bottles, containers, pipes), polystyrene (tanks, containers), polypropylene (tanks, containers), and polyvinylchloride (pipes, containers). Thermoset plastics are formed by the condensation of alcohols or amines to form polyesters or polyamides, and are typically solidified after heating. As opposed to the linear structure of thermoplastic, thermoset plastics have a cross-linked structure which results in higher strength. The most common thermoset plastic is polyurethane which is used for coatings, insulation, paints, and packing. Given both the concerns over pollution reduction and energy conservation, significant efforts are underway on Earth to evaluate biodegradable plastics made from renewable feedstocks; the following summarizes the current state of these efforts. Production of biodegradable plastics involves either the introduction of biodegradable or photo-oxidizable components into the polymer chain or the use of biodegradable polymers themselves. The first approach is based on the observation that polyolefins of low molecular weight (<500 Da) are biodegradable. Insertion of structures susceptible to either photoor chemical degradation within the overall polyolefins chain (which are of 4 - 28 kDa molecular weight), can produce segments sufficiently small to be assimilated and degraded by microorganisms. Biodegradable polymers based strictly on nonpetroleum, biologically-based material have been developed, including some which are used to make currently marketed products. Polyhydroxyalkanoates (PHAs) are polyesters which are accumulated as carbon storage materials by microorganisms under nutrient limiting conditions. MirelTM , a "bioplastic" based on stocktickerPHA produced from microbial fermentation of sugars or oils from vegetables crops, is being produced by TellesTM . The company markets MirelTM bioplastics for use in molding, coatings, films, adhesives, and fibers. Another type of bioplastic is based on polylactic acid, or stocktickerPLA. Starch, typically from corn, is f

  20. Universal fungal vaccines

    PubMed Central

    Hamad, Mawieh

    2012-01-01

    The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks. PMID:22922769