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

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Immunoregulation, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics...

  2. 76 FR 44016 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research...

  3. 77 FR 3780 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. The...

  4. 78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function..., Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. FDA intends to...

  5. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Polysaccharides, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review...

  6. 76 FR 55397 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Laboratory of Method Development, Division of Viral Products, Office of Vaccines Research and Review, Center...

  7. 75 FR 47605 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Laboratory of Vector Borne Virus Diseases, Division of Viral Products, Office of Vaccines Research and Review...

  8. 75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... vaccines for a post-exposure prophylaxis indication using the animal rule. On November 17, 2010, the...

  9. 77 FR 42319 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-18

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... consideration of the appropriateness of cell lines derived from human tumors for vaccine manufacture. FDA...

  10. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... the influenza virus vaccine for the 2011-2012 influenza season. The committee will also hear an update...

  11. 78 FR 5465 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... virus vaccine for the 2013- 2014 influenza season. FDA intends to make background material available to...

  12. 75 FR 2876 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... virus vaccine for the 2010 - 2011 influenza season. FDA intends to make background material available to...

  13. 76 FR 52668 - Vaccines and Related Biological Products Advisory Committee; Amendment of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ...] Vaccines and Related Biological Products Advisory Committee; Amendment of Notice AGENCY: Food and Drug... notice of meeting of the Vaccines and Related Biological Products Advisory Committee. This meeting was... INFORMATION: In the Federal Register of July 22, 2011, FDA announced that a meeting of the Vaccines and...

  14. 76 FR 79203 - Prospective Grant of Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines AGENCY: National Institutes....7. The invention relates to compositions and methods of use as Veterinary Influenza Vaccines... to humans. This technology describes DNA vaccines against influenza serotypes H5N1, H1N1, H3N2, and...

  15. Need for new technologies for detection of adventitious agents in vaccines and other biological products.

    PubMed

    Mallet, Laurent; Gisonni-Lex, Lucy

    2014-01-01

    From an industrial perspective, the conventional in vitro and in vivo assays used for detection of viral contaminants have shown their limitations, as illustrated by the unfortunate detection of porcine circovirus contamination in a licensed rotavirus vaccine. This contamination event illustrates the gaps within the existing adventitious agent strategy and the potential use of new broader molecular detection methods. This paper serves to summarize current testing approaches and challenges, along with opportunities for the use of these new technologies. Testing of biological products is required to ensure the safety of patients. Recently, a licensed vaccine was found to be contaminated with a virus. This contamination did not cause a safety concern to the patients; however, it highlights the need for using new testing methods to control our biological products. This paper introduces the benefits of these new tests and outlines the challenges with the current tests. © PDA, Inc. 2014.

  16. In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

    PubMed Central

    Li, Yi; Beitelshees, Marie; Fang, Lei; Hill, Andrew; Ahmadi, Mahmoud Kamal; Chen, Mingfu; Davidson, Bruce A.; Knight, Paul; Smith, Randall J.; Andreadis, Stelios T.; Hakansson, Anders P.; Jones, Charles H.; Pfeifer, Blaine A.

    2016-01-01

    The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector. PMID:27419235

  17. A survey of the concentrations of eleven metals in vaccines, allergenic extracts, toxoids, blood, blood derivatives and other biological products.

    PubMed

    May, J C; Rains, T C; Maienthal, F J; Biddle, G N; Progar, J J

    1986-10-01

    Approximately 85 samples of injectable biological products regulated by the Center for Drugs and Biologics of the United States Food and Drug Administration were surveyed for the presence of 11 elements, namely aluminum, arsenic, barium, cadmium, chromium, lead, mercury, selenium, thallium and zinc, by flame and flameless methods of atomic absorption spectrometry and flame emission spectrometry. The range of products tested included whole blood, red cells, plasma, normal serum albumin, antihemophilic factor, and other products derived from blood; allergenic extracts including honey bee venom and house dust allergenic extracts; vaccines such as measles virus vaccine and typhoid vaccine; and tetanus toxoid. The metal concentrations found in the majority of these products were low or undetectable. The metal levels varied from manufacturer to manufacturer, product and lot-to-lot of the same manufacturer's products. House dust allergenic extracts had the highest concentrations of arsenic (2.4 ppm), cadmium (0.28 ppm), chromium (0.6 ppm) and lead (1.5 ppm) found in the study. A high zinc concentration (24 ppm) in an immune serum globulin was attributed to the zinc-containing rubber stopper in contact with the product. A range of 0.36-3.30 ppm aluminum was found for seven 25% normal serum albumin samples from seven manufacturers. Values of 8.2, 17 and 18 ppm aluminum were found in one manufacturer's 25% normal serum albumin. These aluminum values appeared to be the result of an anomaly in this manufacturer's production that has not been repeated to date.

  18. 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

  19. Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

    PubMed

    Hall, Victoria; Johnson, Douglas; Torresi, Joseph

    2018-01-01

    Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

  20. 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.

  1. [Building confidence in biological products].

    PubMed

    Rosdahl, Nils; Hardy, Anne

    2006-01-01

    During the last decades of the 19th century, discoveries in microbiology paved the way for health programmes as an integral part of social modernisation. Public opinion about the consequences for governmental involvement differed, but in Denmark the state's openness to modern medicine encouraged the establishment of Statens Serum Institut (SSI) in 1902, initially for the production of anti-diphtheritic serum. Under its director, Thorvald Madsen (1870-1957), the SSI soon acquired a reputation for the high quality of its products and its cutting edge research. After qualifying in medicine in 1893, Madsen worked both at the Pasteur Institute and with Paul Ehrlich in Frankfurt. During World War I, he served with the Red Cross, caring for German, Austrian and Russian prisoners of war. He had an extensive and expanding network of international contacts, and he was eminently qualified to assume the elected office of President of the League of Nations' Health Committee. The Committee served as the 'parliamentary body' of the League of Nations Health Organisation (LNHO), and Madsen's hand can be seen in much of the work undertaken by the LNHO. The drive to achieve uniform standards for biological products related directly to his own as well as the SSI's interests and expertise. Undoubtedly, standardization of biological products had an immense importance for their distribution, scientifically, commercially and therapeutically. Madsen was president of the LNHO's Commission on Biological Standardisation from 1924, and during the interwar years, the SSI was heavily involved in establishing standards for biological products such as tuberculin and tetanus antitoxin. Madsen's interests extended to application of prevention technologies, and he utilised the opportunities in Denmark to further their use, notably in the case of tuberculosis. The introduction of the BCG vaccine promised a solution to the TB problem, but the Lübeck disaster generated a widespread reaction against the

  2. Biological challenges to effective vaccines in the developing world

    PubMed Central

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

    2015-01-01

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

  3. Sex-based biology and the rational design of influenza vaccination strategies.

    PubMed

    Klein, Sabra L; Pekosz, Andrew

    2014-07-15

    Biological (ie, sex) differences as well as cultural (ie, gender) norms influence the acceptance and efficacy of vaccines for males and females. These differences are often overlooked in the design and implementation of vaccination strategies. Using seasonal and pandemic influenza vaccines, we document profound differences between the sexes in the acceptance, correlates of protection, and adverse reactions following vaccination in both young and older adults. Females develop higher antibody responses, experience more adverse reactions to influenza vaccines, and show greater vaccine efficacy than males. Despite greater vaccine efficacy in females, both young and older females are often less likely to accept influenza vaccines than their male counterparts. Identification of the biological mechanisms, including the hormones and genes, that underlie differential responses to vaccination is necessary. We propose that vaccines should be matched to an individual's biological sex, which could involve systematically tailoring diverse types of FDA-approved influenza vaccines separately for males and females. One goal for vaccines designed to protect against influenza and even other infectious diseases should be to increase the correlates of protection in males and reduce adverse reactions in females in an effort to increase acceptance and vaccine-induced protection in both sexes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Different applications of virus-like particles in biology and medicine: Vaccination and delivery systems.

    PubMed

    Shirbaghaee, Zeinab; Bolhassani, Azam

    2016-03-01

    Virus-like particles (VLPs) mimic the whole construct of virus particles devoid of viral genome as used in subunit vaccine design. VLPs can elicit efficient protective immunity as direct immunogens compared to soluble antigens co-administered with adjuvants in several booster injections. Up to now, several prokaryotic and eukaryotic systems such as insect, yeast, plant, and E. coli were used to express recombinant proteins, especially for VLP production. Recent studies are also generating VLPs in plants using different transient expression vectors for edible vaccines. VLPs and viral particles have been applied for different functions such as gene therapy, vaccination, nanotechnology, and diagnostics. Herein, we describe VLP production in different systems as well as its applications in biology and medicine. © 2015 Wiley Periodicals, Inc.

  5. Production of recombinant subunit vaccines: protein immunogens, live delivery systems and nucleic acid vaccines.

    PubMed

    Liljeqvist, S; Ståhl, S

    1999-07-30

    The first scientific attempts to control an infectious disease can be attributed to Edward Jenner, who, in 1796 inoculated an 8-year-old boy with cowpox (vaccinia), giving the boy protection against subsequent challenge with virulent smallpox. Thanks to the successful development of vaccines, many major diseases, such as diphtheria, poliomyelitis and measles, are nowadays kept under control, and in the case of smallpox, the dream of eradication has been fulfilled. Yet, there is a growing need for improvements of existing vaccines in terms of increased efficacy and improved safety, besides the development of completely new vaccines. Better technological possibilities, combined with increased knowledge in related fields, such as immunology and molecular biology, allow for new vaccination strategies. Besides the classical whole-cell vaccines, consisting of killed or attenuated pathogens, new vaccines based on the subunit principle, have been developed, e.g. the Hepatitis B surface protein vaccine and the Haemophilus influenzae type b vaccine. Recombinant techniques are now dominating in the strive for an ideal vaccine, being safe and cheap, heat-stable and easy to administer, preferably single-dose, and capable of inducing broad immune response with life-long memory both in adults and in infants. This review will describe different recombinant approaches used in the development of novel subunit vaccines, including design and production of protein immunogens, the development of live delivery systems and the state-of-the-art for nucleic acids vaccines.

  6. Vaccine production, distribution, access, and uptake.

    PubMed

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

    2011-07-30

    For human vaccines to be available on a global scale, complex production methods, meticulous quality control, and reliable distribution channels are needed to ensure that the products are potent and effective at the point of use. The technologies used to manufacture different types of vaccines can strongly affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. The complexity of manufacturing is compounded by the need for different formulations in different countries and age-groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, to ensure optimum access and uptake, strong partnerships are needed between private manufacturers, regulatory authorities, and national and international public health services. For vaccines whose supply is insufficient to meet demand, prioritisation of target groups can increase the effect of these vaccines. In this report, we draw from our experience of vaccine development and focus on influenza vaccines as an example to consider production, distribution, access, and other factors that affect vaccine uptake and population-level effectiveness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. The search for a promising cell factory system for production of edible vaccine

    PubMed Central

    Barzegari, Abolfazl; Saeedi, Nazli; Zarredar, Habib; Barar, Jaleh; Omidi, Yadollah

    2014-01-01

    Despite worldwide vaccination against devastating diseases for decades, millions of children in remote and impoverished regions of the globe die every year from vaccine-preventable infectious diseases. The reasons for incomplete coverage of vaccination programs are based in part on the relatively high costs of conventional vaccinations, including mass production, refrigeration, transportation, and training as well as funding personnel for their administration. Plant-based edible vaccines (PEVs) have been introduced as a revolutionary cost-effective vaccination modality. However, they suffer from major deficiencies that have restricted their application to bench-scale. This article discusses the deficiencies of PEVs and also provides concise overview on the health-promoting, biological and biotechnological features of spirulina (Arthrospira). In short, we envision that spirulina could be considered as a potential alternative biofactory system to the plants toward the production of edible vaccines in high-yield with low-costs that other hosts cannot yet offer. PMID:25424962

  8. 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

  9. Challenges in vaccinating infants born to mothers taking immunoglobulin biologicals during pregnancy.

    PubMed

    Ling, Juejing; Koren, Gideon

    2016-01-01

    While immunoglobulin biologicals are increasingly used during pregnancy, there have been concerns on the immune function and vaccination of infants born to mothers taking immunoglobulin biologicals. In addition to the detection of biologicals in cord blood, cases of severe neonatal neutropenia and fatal dissemination of Bacillus Calmette-Guérin (BCG) have been reported. With increasing number of infants exposed to immunoglobulin biologicals in utero, there is a need to address the challenges in vaccinating these infants. This review summarizes the available evidence to discuss the issues of immunoglobulin biological exposure in utero, neonatal immune function, long-term immune development, and the challenges and strategies of vaccinating newborns and infants who were born to mothers taking biologicals during pregnancy.

  10. Systems biology and the quest for correlates of protection to guide the development of an HIV vaccine.

    PubMed

    Kuri-Cervantes, Leticia; Fourati, Slim; Canderan, Glenda; Sekaly, Rafick-Pierre

    2016-08-01

    Over the last three decades, a myriad of data has been generated regarding HIV/SIV evolution, immune evasion, immune response, and pathogenesis. Much of this data can be integrated and potentially used to generate a successful vaccine. Although individual approaches have begun to shed light on mechanisms involved in vaccine-conferred protection from infection, true correlates of protection have not yet been identified. The systems biology approach helps unify datasets generated using different techniques and broaden our understanding of HIV immunopathogenesis. Moreover, systems biology is a tool that can provide correlates of protection, which can be targeted for the production of a successful HIV vaccine. Copyright © 2016. Published by Elsevier Ltd.

  11. Chinese vaccine products go global: vaccine development and quality control.

    PubMed

    Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

    2015-05-01

    Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

  12. Systems Vaccinology: Enabling rational vaccine design with systems biological approaches

    PubMed Central

    Hagan, Thomas; Nakaya, Helder I.; Subramaniam, Shankar; Pulendran, Bali

    2015-01-01

    Vaccines have drastically reduced the mortality and morbidity of many diseases. However, vaccines have historically been developed empirically, and recent development of vaccines against current pandemics such as HIV and malaria has been met with difficulty. The advent of high-throughput technologies, coupled with systems biological methods of data analysis, has enabled researchers to interrogate the entire complement of a variety of molecular components within cells, and characterize the myriad interactions among them in order to model and understand the behavior of the system as a whole. In the context of vaccinology, these tools permit exploration of the molecular mechanisms by which vaccines induce protective immune responses. Here we review the recent advances, challenges, and potential of systems biological approaches in vaccinology. If the challenges facing this developing field can be overcome, systems vaccinology promises to empower the identification of early predictive signatures of vaccine response, as well as novel and robust correlates of protection from infection. Such discoveries, along with the improved understanding of immune responses to vaccination they impart, will play an instrumental role in development of the next generation of rationally designed vaccines. PMID:25858860

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.

    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 enhancedmore » 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

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

    PubMed

    Kim, So Youn; Cho, Jahyang; Cha, Sung-Ho; Bae, Chong-Woo

    2013-07-01

    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. Statistical data were obtained from the Bank of Korea, Korea Health Industry Development Institute, Korea Pharmaceutical Traders Association, and Korea Pharmaceutical Manufacturers Association. 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. 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.

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

    PubMed

    Adams, L Garry; 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 ΔsipA, 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

  16. A comparison of the oral application and injection routes using the onderstepoort biological products fowl typhoid vaccine, its safety, efficacy and duration of protection in commercial laying hens.

    PubMed

    Purchase, C; Picard, J; McDonald, R; Bisschop, S P R

    2008-03-01

    This study was undertaken to establish whether the Onderstepoort Biological Products Fowl Typhoid (OBPft) vaccine registered as an injectable vaccine was effective and safe when administered orally to commercial layers. Its efficacy and duration of protection were compared with application by intramuscular injection. Commercial brown layer hens were used as they were found to be highly susceptible to Salmonella gallinarum infections. In the vaccine safety trial birds were euthanased at timed intervals spanning 4 weeks postvaccination. Necropsies were performed and samples were taken and tested. No clinical signs or mortalities could be attributed to the OBPft vaccine nor could active shedding of the vaccine strain be detected. Slight pathological changes were noted with both routes of vaccination; however, these changes were transient, returning to normal within the observation period. The injected groups showed a better serological response with the rapid serum plate agglutination (RSPA) test than the orally vaccinated groups. In the duration of protection trial, birds were challenged at 3-8-week intervals post-vaccination. All unvaccinated birds died. Protection 8 and 16 weeks after vaccination was above 60 %,by 24 weeks after challenge, the vaccine protection was below 30 %. It was found that there was no significant difference (P < 0.05) in the protection offered by either the oral or injected route of vaccination with the OBPft vaccine.

  17. Smallpox and biological warfare: the case for abandoning vaccination of military personnel.

    PubMed Central

    Capps, L; Vermund, S H; Johnsen, C

    1986-01-01

    Smallpox was officially declared eradicated from the world in 1980. Earlier, in 1972, over 50 nations signed the Biological Weapons Convention renouncing this entire category of weapons. Despite this international agreement, both the United States and the Soviet Union continue to vaccinate their military troops against smallpox, thus implying that each fears the other might still use it in biological warfare. Vaccination is not a harmless procedure, and vaccinia infections continue to be reported in troops and their contacts. Negotiating an end to the vaccination of troops would be a final step in ending the fear of smallpox. PMID:2944401

  18. New approaches for antigen discovery, production and delivery: vaccines for veterinary and human use.

    PubMed

    Potter, A A; Babiuk, L A

    2001-11-01

    Vaccination of individuals has been practiced for many years and has been one of the most effective methods of controlling infectious diseases. Unfortunately, even with this success, society continues to suffer multi-billion dollar economic losses annually due to infectious diseases. These losses occur in all animal species as well as in humans. In order to further reduce these losses, academicians and companies are employing the multidisciplinary approach to develop better and safer vaccines. These include capitalizing on advances in molecular biology, chemistry, pharmacy, immunology, genomics, proteomics, and fermentation. Thus, we are moving from a more empirical approach to vaccine production to a more focused, and, hopefully, more logical approach to identification and production of protective antigens. Furthermore, formulation and delivery of these antigens in playing a major role in revolutionizing how we deliver vaccines to induce the most appropriate immune response and ensure protection. The current review summarizes some of these advances and speculates as to how future vaccines will be produced and delivered for the benefit of society.

  19. Evaluation of growth based rapid microbiological methods for sterility testing of vaccines and other biological products.

    PubMed

    Parveen, Seema; Kaur, Simleen; David, Selwyn A Wilson; Kenney, James L; McCormick, William M; Gupta, Rajesh K

    2011-10-19

    Most biological products, including vaccines, administered by the parenteral route are required to be tested for sterility at the final container and also at various stages during manufacture. The sterility testing method described in the Code of Federal Regulations (21 CFR 610.12) and the United States Pharmacopoeia (USP, Chapter <71>) is based on the observation of turbidity in liquid culture media due to growth of potential contaminants. We evaluated rapid microbiological methods (RMM) based on detection of growth 1) by adenosine triphosphate (ATP) bioluminescence technology (Rapid Milliflex(®) Detection System [RMDS]), and 2) by CO(2) monitoring technologies (BacT/Alert and the BACTEC systems), as alternate sterility methods. Microorganisms representing Gram negative, Gram positive, aerobic, anaerobic, spore forming, slow growing bacteria, yeast, and fungi were prepared in aliquots of Fluid A or a biological matrix (including inactivated influenza vaccines) to contain approximately 0.1, 1, 10 and 100 colony forming units (CFU) in an inoculum of 10 ml. These preparations were inoculated to the specific media required for the various methods: 1) fluid thioglycollate medium (FTM) and tryptic soy broth (TSB) of the compendial sterility method (both membrane filtration and direct inoculation); 2) tryptic soy agar (TSA), Sabouraud dextrose agar (SDA) and Schaedler blood agar (SBA) of the RMDS; 3) iAST and iNST media of the BacT/Alert system and 4) Standard 10 Aerobic/F and Standard Anaerobic/F media of the BACTEC system. RMDS was significantly more sensitive in detecting various microorganisms at 0.1CFU than the compendial methods (p<0.05), whereas the compendial membrane filtration method was significantly more sensitive than the BACTEC and BacT/Alert methods (p<0.05). RMDS detected all microorganisms significantly faster than the compendial method (p<0.05). BacT/Alert and BACTEC methods detected most microorganisms significantly faster than the compendial method

  20. 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.

  1. Safety of plant-made pharmaceuticals: product development and regulatory considerations based on case studies of two autologous human cancer vaccines.

    PubMed

    Tusé, Daniel

    2011-03-01

    Guidelines issued by regulatory agencies for the development of plant-made pharmaceutical (PMP) products provide criteria for product manufacturing and characterization, safety determination, containment and mitigation of environmental risks. Features of plant-made products do not always enable an easy fit within the criteria subscribed to by regulators. The unconventional nature of plant-based manufacturing processes and peculiarities of plant biology relative to that of traditional biological production systems have led to special considerations in the regulatory scrutiny of PMP. Presented in this review are case studies of two plant-made autologous (patient-specific) cancer vaccines, the nature of which introduced challenges to conventional and standardized development and preclinical evaluation routes. The rationale presented to FDA by the sponsors of each vaccine to build consensus and obtain variances to existing guidelines is discussed. While development of many plant-made biologics can be accomplished within the existing regulatory framework, the development of specialized products can be defended with rational arguments based on strong science.

  2. Automated production of plant-based vaccines and pharmaceuticals.

    PubMed

    Wirz, Holger; Sauer-Budge, Alexis F; Briggs, John; Sharpe, Aaron; Shu, Sudong; Sharon, Andre

    2012-12-01

    A fully automated "factory" was developed that uses tobacco plants to produce large quantities of vaccines and other therapeutic biologics within weeks. This first-of-a-kind factory takes advantage of a plant viral vector technology to produce specific proteins within the leaves of rapidly growing plant biomass. The factory's custom-designed robotic machines plant seeds, nurture the growing plants, introduce a viral vector that directs the plant to produce a target protein, and harvest the biomass once the target protein has accumulated in the plants-all in compliance with Food and Drug Administration (FDA) guidelines (e.g., current Good Manufacturing Practices). The factory was designed to be time, cost, and space efficient. The plants are grown in custom multiplant trays. Robots ride up and down a track, servicing the plants and delivering the trays from the lighted, irrigated growth modules to each processing station as needed. Using preprogrammed robots and processing equipment eliminates the need for human contact, preventing potential contamination of the process and economizing the operation. To quickly produce large quantities of protein-based medicines, we transformed a laboratory-based biological process and scaled it into an industrial process. This enables quick, safe, and cost-effective vaccine production that would be required in case of a pandemic.

  3. Canadian regulatory requirements for recombinant fish vaccines.

    PubMed

    Sethi, M S; Gifford, G A; Samagh, B S

    1997-01-01

    In Canada, veterinary biological products derived by using conventional and new techniques of biotechnology are licensed and regulated under the Health of Animals Act and Regulations. Biological products include vaccines, bacterins, bacterin-toxoids and diagnostic kits which are used for the prevention, treatment or diagnosis of infectious diseases in all species of animals, including fish. Veterinary biologicals are licensed on the basis of fulfillment of four criteria: purity, potency, safety and efficacy. A risk-based approach is used to evaluate the safety of the product in target species, as well as non-target species, humans and the environment. On the basis of biological characteristics, biotechnology derived veterinary biologicals have been divided into two broad categories, high and low risk products. The paper describes the regulatory framework for the licensing of veterinary biologicals in Canada, with emphasis on the regulatory considerations for recombinant fish vaccines. Stages of movement of the product from research in a contained laboratory facility to a fully licensed product for free sale are discussed. The requirements for field testing and environmental assessment involved in these stages are highlighted. Manufacturers and researchers who intend to commercialize experimental vaccines are encouraged to consult with the Veterinary Biologics and Biotechnology Section early in the product development process so that the research data and quality assurance documentation are consistent with regulatory requirements.

  4. EDQM biological reference preparation for rabies vaccine (inactivated) for veterinary use.

    PubMed

    Daas, A; Bruckner, L; Milne, C

    2015-01-01

    Rabies is a deadly zoonotic disease. Control of rabies in animals by vaccination is an important strategy to protect humans from infection and control the spread of the disease. Requirements for the quality control of rabies vaccines (inactivated) for veterinary use include an in vivo quantitative potency determination as outlined in the Ph. Eur. monograph 0451. Performance of this assay requires a reference preparation calibrated in International Units (IU). A European Pharmacopeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccines (inactivated) for veterinary use, calibrated in IU, has been established for this purpose. Due to the dwindling stocks of the current batch (batch 4) of Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use, a collaborative study was run as part of the EDQM Biological Standardisation Programme to establish BRP batch 5. Ten laboratories, including Official Medicines Control Laboratories and manufacturers, participated. The candidate BRP5 was assayed against the 6(th) International Standard for rabies vaccine using the in vivo vaccination-challenge assay (monograph 0451) to assign a potency value. The candidate was also compared to BRP batch 4 to establish continuity. Taking into account the results from the comparisons a potency of 10 IU/vial was assigned and in March 2015 the Ph. Eur. Commission adopted the material as Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use batch 5. In addition to the in vivo assay 3 laboratories tested the candidate material using their in-house in vitro assays for information.

  5. Considerations for sustainable influenza vaccine production in developing countries.

    PubMed

    Nannei, Claudia; Chadwick, Christopher; Fatima, Hiba; Goldin, Shoshanna; Grubo, Myriam; Ganim, Alexandra

    2016-10-26

    Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. U.S. vaccine and immune globulin product shortages, 2001-15.

    PubMed

    Ziesenitz, Victoria C; Mazer-Amirshahi, Maryann; Zocchi, Mark S; Fox, Erin R; May, Larissa S

    2017-11-15

    Trends in shortages of vaccines and immune globulin products from 2001 through 2015 in the United States are described. Drug shortage data from January 2001 through December 2015 were obtained from the University of Utah Drug Information Service. Shortage data for vaccines and immune globulins were analyzed, focusing on the type of product, reason for shortage, shortage duration, shortages requiring vaccine deferral, and whether the drug was a single-source product. Inclusion of the product into the pediatric vaccination schedule was also noted. Of the 2,080 reported drug shortages, 59 (2.8%) were for vaccines and immune globulin products. Of those, 2 shortages (3%) remained active at the end of the study period. The median shortage duration was 16.8 months. The most common products on shortage were viral vaccines (58%), especially hepatitis A, hepatitis B, rabies, and varicella vaccines (4 shortages each). A vaccine deferral was required for 21 shortages (36%), and single-source products were on shortage 30 times (51%). The most common reason for shortage was manufacturing problems (51%), followed by supply-and-demand issues (7%). Thirty shortages (51%) were for products on the pediatric schedule, with a median duration of 21.7 months. Drug shortages of vaccines and immune globulin products accounted for only 2.8% of reported drug shortages within a 15-year period, but about half of these shortages involved products on the pediatric vaccination schedule, which may have significant public health implications. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Ontology-supported Research on Vaccine Efficacy, Safety, and Integrative Biological Networks

    PubMed Central

    He, Yongqun

    2016-01-01

    Summary 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 the 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

  8. Comparison of Biological Activity of Human Anti-Apical Membrane Antigen-1 Antibodies Induced by Natural Infection and Vaccination

    PubMed Central

    Miura, Kazutoyo; Zhou, Hong; Moretz, Samuel E.; Diouf, Ababacar; Thera, Mahamadou A; Dolo, Amagana; Doumbo, Ogobara; Malkin, Elissa; Diemert, David; Miller, Louis H.; Mullen, Gregory E.D.; Long, Carole A.

    2009-01-01

    Vaccines represent a significant potential means of decreasing global morbidity and mortality due to malaria. Clinical trials in the U.S. with Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) showed that the vaccine induced biologically active antibodies judged by an in vitro parasite Growth Inhibition Assay (GIA). However, the same vaccine in Malian adults did not increase biological activity although it elevated ELISA titers. As GIA has been used to evaluate the biological activity of antibodies induced by blood-stage malarial vaccine candidates, we explored this discrepancy in this study. We affinity purified AMA1-specific antibodies from both US vaccinees and from non-vaccinated individuals living in a malaria-endemic area of Mali, and performed ELISA and GIA. Both AMA1-specifc antibodies induced by vaccination (US) and by natural infection (Mali) have comparable biological activity in GIA when the ELISA titer is normalized. However, a fraction of Malians’ IgG which did not bind to AMA1 protein (Mali-non-AMA1 IgG) reduced the biological activity of the AMA1 antibodies from US vaccinees; in contrast, US-non-AMA1 IgGs did not show a reduction of the biological activity. Further investigation revealed that the reduction was due to malaria-specific IgGs in the Mali-non-AMA1 IgGs. The fact that both US- and Mali-AMA1-specific antibodies showed comparable biological activity supports further development of AMA1-based vaccines. However, the reduction of biological activity of AMA1-specific antibody by other malaria-specific IgGs likely explains the limited effect on growth-inhibitory activity of antibodies induced by AMA1 vaccination in Malian adults and may complicate efforts to develop a blood-stage malaria vaccine. PMID:19050299

  9. WHO Expert Committee on Biological Standardization.

    PubMed

    2002-01-01

    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 quality 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 issues relevant to international guidelines, recommendations and other matters related to the manufacture and quality control of biologicals. This is followed by information on the status and development of reference materials for bovine spongiform encephalopathy, various antigens, blood products, cytokines, growth factors and endocrinological substances. The second part of the report, of particular interest to manufacturers and national control authorities, contains sets of recommendations for the production and control of poliomyelitis vaccine (oral) and poliomyelitis vaccine (inactivated) and guidelines for the production and control of live attenuated Japanese encephalitis vaccine. Also included are lists of recommendations and guidelines for biological substances used in medicine, and other relevant documents.

  10. Development of Special Biological Products

    DTIC Science & Technology

    1981-01-01

    Rocky Mountain Spotted Fever (RMSF) 20. Continued B. Tissue Culture / ?Two production lots of FRhL-2 dnd three of MRC-5 were stabilized...104) was potency tested. J. Q Fever Vaccine Storage Stability Potency Testing Q fever vaccine (NDBR 105) was put on potency test. K. Rocky Mountain Spotted Fever (RMSF...Fever Vaccine Storage Stability Potency Testing Two lots of Q fever vaccine (NDBR 105) were put on potency test. K. Rocky Mountain Spotted Fever

  11. The 2015 global production capacity of seasonal and pandemic influenza vaccine.

    PubMed

    McLean, Kenneth A; Goldin, Shoshanna; Nannei, Claudia; Sparrow, Erin; Torelli, Guido

    2016-10-26

    A global shortage and inequitable access to influenza vaccines has been cause for concern for developing countries who face dire consequences in the event of a pandemic. The Global Action Plan for Influenza Vaccines (GAP) was launched in 2006 to increase global capacity for influenza vaccine production to address these concerns. It is widely recognized that well-developed infrastructure to produce seasonal influenza vaccines leads to increased capacity to produce pandemic influenza vaccines. This article summarizes the results of a survey administered to 44 manufacturers to assess their production capacity for seasonal influenza and pandemic influenza vaccine production. When the GAP was launched in 2006, global production capacity for seasonal and pandemic vaccines was estimated to be 500million and 1.5billion doses respectively. Since 2006 there has been a significant increase in capacity, with the 2013 survey estimating global capacity at 1.5billion seasonal and 6.2billion pandemic doses. Results of the current survey showed that global seasonal influenza vaccine production capacity has decreased since 2013 from 1.504billion doses to 1.467billion doses. However, notwithstanding the overall global decrease in seasonal vaccine capacity there were notable positive changes in the distribution of production capacity with increases noted in South East Asia (SEAR) and the Western Pacific (WPR) regions, albeit on a small scale. Despite a decrease in seasonal capacity, there has been a global increase of pandemic influenza vaccine production capacity from 6.2 billion doses in 2013 to 6.4 billion doses in 2015. This growth can be attributed to a shift towards more quadrivalent vaccine production and also to increased use of adjuvants. Pandemic influenza vaccine production capacity is at its highest recorded levels however challenges remain in maintaining this capacity and in ensuring access in the event of a pandemic to underserved regions. Copyright © 2016. Published by

  12. Overview of measles and mumps vaccine: origin, present, and future of vaccine production.

    PubMed

    Betáková, T; Svetlíková, D; Gocník, M

    2013-01-01

    Measles and mumps are common viral childhood diseases that can cause serious complications. Vaccination remains the most efficient way to control the spread of these viruses. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblast or primary dog kidney cell substrates, is no longer sufficient. This limitation can be overcome by utilizing other recognized cell substrates such as Madin Darby Canine Kidney (MDCK), Chinese Hamster Ovary (CHO), Vero (monkey origin) cells, MRC-5 (human diploid) or as an alternative, introducing new cell substrates of human or avian origin. A very important factor in vaccine production is the safety and immunogenicity of the final vaccine, where the proper choice of cell substrate used for virus propagation is made. All substrates used in vaccine production must be fully characterized to avoid the contamination of hidden unknown pathogens which is difficult to achieve in primary cell substrates.

  13. Sustainable vaccine development: a vaccine manufacturer's perspective.

    PubMed

    Rappuoli, Rino; Hanon, Emmanuel

    2018-05-08

    Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health. Copyright © 2018 GlaxoSmithKine Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  14. Current biodefense vaccine programs and challenges.

    PubMed

    Wolfe, Daniel N; Florence, William; Bryant, Paula

    2013-07-01

    The Defense Threat Reduction Agency's Joint Science and Technology Office manages the Chemical and Biological Defense Program's Science and Technology portfolio. The Joint Science and Technology Office's mission is to invest in transformational ideas, innovative people and actionable technology development for Chemical and Biological Defense solutions, with the primary goal to deliver Science and Technology products and capabilities to the warfighter and civilian population that outpace the threat. This commentary focuses on one thrust area within this mission: the Vaccine program of the Joint Science and Technology Office's Translational Medical Division. Here, we will describe candidate vaccines currently in the S&T pipeline, enabling technologies that should facilitate advanced development of these candidates into FDA licensed vaccines, and how the ever-changing biological threat landscape impacts the future of biodefense vaccines.

  15. Hijacking bacterial glycosylation for the production of glycoconjugates, from vaccines to humanised glycoproteins.

    PubMed

    Cuccui, Jon; Wren, Brendan

    2015-03-01

    Glycosylation or the modification of a cellular component with a carbohydrate moiety has been demonstrated in all three domains of life as a basic post-translational process important in a range of biological processes. This review will focus on the latest studies attempting to exploit bacterial N-linked protein glycosylation for glycobiotechnological applications including glycoconjugate vaccine and humanised glycoprotein production. The challenges that remain for these approaches to reach full biotechnological maturity will be discussed. Oligosaccharyltransferase-dependent N-linked glycosylation can be exploited to make glycoconjugate vaccines against bacterial pathogens. Few technical limitations remain, but it is likely that the technologies developed will soon be considered a cost-effective and flexible alternative to current chemical-based methods of vaccine production. Some highlights from current glycoconjugate vaccines developed using this in-vivo production system include a vaccine against Shigella dysenteriae O1 that has passed phase 1 clinical trials, a vaccine against the tier 1 pathogen Francisella tularensis that has shown efficacy in mice and a vaccine against Staphylococcus aureus serotypes 5 and 8. Generation of humanised glycoproteins within bacteria was considered impossible due to the distinct nature of glycan modification in eukaryotes and prokaryotes. We describe the method used to overcome this conundrum to allow engineering of a eukaryotic pentasaccharide core sugar modification within Escherichia coli. This core was assembled by combining the function of the initiating transferase WecA, several Alg genes from Saccharomyces cerevisiae and the oligosaccharyltransferase function of the Campylobacter jejuni PglB. Further exploitation of a cytoplasmic N-linked glycosylation system found in Actinobacillus pleuropneumoniae where the central enzyme is known as N-linking glycosyltransferase has overcome some of the limitations demonstrated by the

  16. Laboratory tests for mumps vaccines.

    PubMed

    Minor, P D

    1997-03-01

    The action of live attenuated vaccines against mumps is poorly understood although their clinical efficacy is beyond doubt. The attenuated character of the vaccine is assured by consistency of production related to clinical trials, and limited studies of vaccine seeds in primates. Potency is assessed by infectivity in vitro and is subject to poorly understood sources of variation. Molecular biological studies are at an early stage.

  17. Structural and Computational Biology in the Design of Immunogenic Vaccine Antigens

    PubMed Central

    Liljeroos, Lassi; Malito, Enrico; Ferlenghi, Ilaria; Bottomley, Matthew James

    2015-01-01

    Vaccination is historically one of the most important medical interventions for the prevention of infectious disease. Previously, vaccines were typically made of rather crude mixtures of inactivated or attenuated causative agents. However, over the last 10–20 years, several important technological and computational advances have enabled major progress in the discovery and design of potently immunogenic recombinant protein vaccine antigens. Here we discuss three key breakthrough approaches that have potentiated structural and computational vaccine design. Firstly, genomic sciences gave birth to the field of reverse vaccinology, which has enabled the rapid computational identification of potential vaccine antigens. Secondly, major advances in structural biology, experimental epitope mapping, and computational epitope prediction have yielded molecular insights into the immunogenic determinants defining protective antigens, enabling their rational optimization. Thirdly, and most recently, computational approaches have been used to convert this wealth of structural and immunological information into the design of improved vaccine antigens. This review aims to illustrate the growing power of combining sequencing, structural and computational approaches, and we discuss how this may drive the design of novel immunogens suitable for future vaccines urgently needed to increase the global prevention of infectious disease. PMID:26526043

  18. Structural and Computational Biology in the Design of Immunogenic Vaccine Antigens.

    PubMed

    Liljeroos, Lassi; Malito, Enrico; Ferlenghi, Ilaria; Bottomley, Matthew James

    2015-01-01

    Vaccination is historically one of the most important medical interventions for the prevention of infectious disease. Previously, vaccines were typically made of rather crude mixtures of inactivated or attenuated causative agents. However, over the last 10-20 years, several important technological and computational advances have enabled major progress in the discovery and design of potently immunogenic recombinant protein vaccine antigens. Here we discuss three key breakthrough approaches that have potentiated structural and computational vaccine design. Firstly, genomic sciences gave birth to the field of reverse vaccinology, which has enabled the rapid computational identification of potential vaccine antigens. Secondly, major advances in structural biology, experimental epitope mapping, and computational epitope prediction have yielded molecular insights into the immunogenic determinants defining protective antigens, enabling their rational optimization. Thirdly, and most recently, computational approaches have been used to convert this wealth of structural and immunological information into the design of improved vaccine antigens. This review aims to illustrate the growing power of combining sequencing, structural and computational approaches, and we discuss how this may drive the design of novel immunogens suitable for future vaccines urgently needed to increase the global prevention of infectious disease.

  19. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach.

    PubMed

    Lambert, Nathaniel D; Ovsyannikova, Inna G; Pankratz, V Shane; Jacobson, Robert M; Poland, Gregory A

    2012-08-01

    Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults.

  20. African Swine Fever Virus Biology and Vaccine Approaches.

    PubMed

    Revilla, Yolanda; Pérez-Núñez, Daniel; Richt, Juergen A

    2018-01-01

    African swine fever (ASF) is an acute and often fatal disease affecting domestic pigs and wild boar, with severe economic consequences for affected countries. ASF is endemic in sub-Saharan Africa and the island of Sardinia, Italy. Since 2007, the virus emerged in the republic of Georgia, and since then spread throughout the Caucasus region and Russia. Outbreaks have also been reported in Belarus, Ukraine, Lithuania, Latvia, Estonia, Romania, Moldova, Czech Republic, and Poland, threatening neighboring West European countries. The causative agent, the African swine fever virus (ASFV), is a large, enveloped, double-stranded DNA virus that enters the cell by macropinocytosis and a clathrin-dependent mechanism. African Swine Fever Virus is able to interfere with various cellular signaling pathways resulting in immunomodulation, thus making the development of an efficacious vaccine very challenging. Inactivated preparations of African Swine Fever Virus do not confer protection, and the role of antibodies in protection remains unclear. The use of live-attenuated vaccines, although rendering suitable levels of protection, presents difficulties due to safety and side effects in the vaccinated animals. Several African Swine Fever Virus proteins have been reported to induce neutralizing antibodies in immunized pigs, and vaccination strategies based on DNA vaccines and recombinant proteins have also been explored, however, without being very successful. The complexity of the virus particle and the ability of the virus to modulate host immune responses are most likely the reason for this failure. Furthermore, no permanent cell lines able to sustain productive virus infection by both virulent and naturally attenuated African Swine Fever Virus strains exist so far, thus impairing basic research and the commercial production of attenuated vaccine candidates. © 2018 Elsevier Inc. All rights reserved.

  1. Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development

    PubMed Central

    Wirsing von König, Carl Heinz; Lan, Ruiting; Cotter, Peggy A.; Deora, Rajendar; Merkel, Tod J.; van Els, Cécile A.; Locht, Camille; Hozbor, Daniela; Rodriguez, Maria E.

    2016-01-01

    Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis. The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals. PMID:27655886

  2. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

    PubMed

    Fox, Christopher B

    2013-09-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted.

  3. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING... Disease Vaccine. (2) Poultry vaccines administered to individual birds using automatic vaccinating..., unless each final container bears, or is packaged in a carton with, complete and approved labeling which...

  4. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING... Disease Vaccine. (2) Poultry vaccines administered to individual birds using automatic vaccinating..., unless each final container bears, or is packaged in a carton with, complete and approved labeling which...

  5. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING... Disease Vaccine. (2) Poultry vaccines administered to individual birds using automatic vaccinating..., unless each final container bears, or is packaged in a carton with, complete and approved labeling which...

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

    PubMed

    Weli, Simon C; Tryland, Morten

    2011-02-03

    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.

  7. Cell culture-derived influenza vaccines from Vero cells: a new horizon for vaccine production.

    PubMed

    Montomoli, Emanuele; Khadang, Baharak; Piccirella, Simona; Trombetta, Claudia; Mennitto, Elisa; Manini, Ilaria; Stanzani, Valerio; Lapini, Giulia

    2012-05-01

    In the 20th century, three influenza pandemics killed approximately 100 million people. The traditional method of influenza vaccine manufacturing is based on using chicken eggs. However, the necessity of the availability of millions of fertile eggs in the event of a pandemic has led research to focus on the development of cell culture-derived vaccines, which offer shorter lead-in times and greater flexibility of production. So far, the cell substrates being evaluated and in use include Vero, Madin-Darby canine kidney, PER.C6 and insect cells. However, Vero cells are the most widely accepted among others. This review introduces briefly the concepts of advanced cell culture-derived influenza vaccine production and highlights the advantages of these vaccines in terms of efficiency, speed and immunogenicity based on the clinical data obtained from different studies.

  8. Production and evaluation of a chromatographically purified Vero cell rabies vaccine (PVRV) in China using microcarrier technology

    PubMed Central

    Yu, Pengcheng; Huang, Ying; Zhang, Yibin; Tang, Qing; Liang, Guodong

    2012-01-01

    China is a high population country with millions of animal bite cases every year; thus, it is necessary to explore and develop more effective and productive rabies vaccines for human use. To establish a safe, effective, inexpensive and high-yield rabies vaccine, a non-adjuvant purified Vero cell rabies vaccine produced in the SPEEDA PVRV microcarrier bioreactor was developed by Liaoning Chengda Biology Co. Ltd. in China. This vaccine was produced using Vero cells that were cultured in a microcarrier bioreactor. A microcarrier bioreactor containing 25 g/L of Cytodex-1 was used for perfusion culture. The Vero cell culture density was up to 1.2–1.5 × 107 cells/ml, viruses could be constantly harvested for 18–22 days, and the resulting vaccine immunizing potency was ≥ 4.5 IU/ml. Vaccine safety and immunogenicity post-immunization were also assessed. A total of 602 volunteers were enrolled and divided into two groups that were vaccinated with either SPEEDA PVRV or VERORAB PVRV on days 0, 3, 7, 14 and 28. All subjects vaccinated with SPEEDA PVRV showed no serious local or systemic adverse effects. The positive conversion rate of serum neutralizing antibodies against the rabies virus reached 100% in both the test and control groups (inoculated with VERORAB PVRV) at 14 days and 45 days after vaccination, and no significant difference was found between the neutralizing antibody geometric mean titers (GMTs) of the two groups. SPEEDA PVRV is appropriate for mass production and shows satisfactory clinical safety and immunogenicity for human post-exposure prophylaxis of rabies. PMID:22894963

  9. Validation of the safety of MDCK cells as a substrate for the production of a cell-derived influenza vaccine.

    PubMed

    Onions, David; Egan, William; Jarrett, Ruth; Novicki, Deborah; Gregersen, Jens-Peter

    2010-09-01

    Cell culture-based production methods may assist in meeting increasing demand for seasonal influenza vaccines and developing production flexibility required for addressing influenza pandemics. MDCK-33016PF cells are used in propagation of a cell-based seasonal influenza vaccine (Optaflu); but, like most continuous cell lines, can grow in immunocompromised mice to produce tumors. It is, therefore, essential that no residual cells remain within the vaccine, that cell lysates or DNA are not oncogenic, and that the cell substrate does not contain oncogenic viruses or oncogenic DNA. Multiple, redundant processes ensure the safety of influenza vaccines produced in MDCK-33016PF cells. The probability of a residual cell being present in a dose of vaccine is approximately 1 in 10(34). Residual MDCK-DNA is < or =10 ng per dose and the ss-propiolactone used to inactivate influenza virus results in reduction of detectable DNA to less than 200 base pairs (bp). Degenerate PCR and specific PCR confirm exclusion of oncogenic viruses. The manufacturing process has been validated for its capacity to remove and inactivate viruses. We conclude that the theoretical risks arising from manufacturing seasonal influenza vaccine using MDCK-33016PF cells are reduced to levels that are effectively zero by the multiple, orthogonal processes used during production. Copyright 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  10. Challenges and opportunities in developing and marketing vaccines for OIE List A and emerging animal diseases.

    PubMed

    Gay, C G; Salt, J; Balaski, C

    2003-01-01

    Veterinary pharmaceutical products generated 14.5 billion U.S. Dollars (USD) in worldwide sales in 2000, with biological products contributing 16.2 percent or 2.3 billion USD. The leading biological products were foot-and-mouth disease (FMD) vaccines, with 284 million USD in sales, representing 26.4 percent of the entire livestock biological business. Despite the potential opportunities for the biologicals industry, non-vaccination policies and undefined control and eradication strategies have deterred the private sector from significant investments in the research and development of vaccines against List A diseases. The primary research focus remains vaccines for infectious diseases that have an impact on current domestic herd health management systems. Changing the vaccine paradigm, investing in new technologies, and creating the future by integrating into key alliances with producers and regulatory authorities will be paramount in protecting our poultry and livestock industries against highly infectious diseases and potential acts of bioterrorism.

  11. Influenza virus surveillance, vaccine strain selection, and manufacture.

    PubMed

    Stöhr, Klaus; Bucher, Doris; Colgate, Tony; Wood, John

    2012-01-01

    As outlined in other chapters, the influenza virus, existing laboratory diagnostic abilities, and disease epidemiology have several peculiarities that impact on the timing and processes for the annual production of influenza vaccines. The chapter provides an overview on the key biological and other factors that influence vaccine production. They are the reason for an "annual circle race" beginning with global influenza surveillance during the influenza season in a given year to the eventual supply of vaccines 12 months later in time before the next seasonal outbreak and so on. As influenza vaccines are needed for the Northern and Southern Hemisphere outbreaks in fall and spring, respectively, global surveillance and vaccine production has become a year round business. Its highlights are the WHO recommendations on vaccine strains in February and September and the eventual delivery of vaccine doses in time before the coming influenza season. In between continues vaccine strain and epidemiological surveillance, preparation of new high growth reassortments, vaccine seed strain preparation and development of standardizing reagents, vaccine bulk production, fill-finishing and vaccine release, and in some regions, clinical trials for regulatory approval.

  12. 9 CFR 113.26 - Detection of viable bacteria and fungi except in live vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Detection of viable bacteria and fungi except in live vaccine. 113.26 Section 113.26 Animals and Animal Products ANIMAL AND PLANT HEALTH... in live vaccine. Each serial and subserial of biological product except live vaccines shall be tested...

  13. 9 CFR 113.26 - Detection of viable bacteria and fungi except in live vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Detection of viable bacteria and fungi except in live vaccine. 113.26 Section 113.26 Animals and Animal Products ANIMAL AND PLANT HEALTH... in live vaccine. Each serial and subserial of biological product except live vaccines shall be tested...

  14. 9 CFR 113.26 - Detection of viable bacteria and fungi except in live vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Detection of viable bacteria and fungi except in live vaccine. 113.26 Section 113.26 Animals and Animal Products ANIMAL AND PLANT HEALTH... in live vaccine. Each serial and subserial of biological product except live vaccines shall be tested...

  15. 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.

  16. Evaluation of pneumococcal and influenza vaccination coverage in rheumatology patients receiving biological therapy in a regional referral hospital.

    PubMed

    Fernández-Prada, María; Brandy-García, Anahy María; Rodríguez-Fonseca, Omar Darío; Huerta-González, Ismael; Fernández-Noval, Federico; Martínez-Ortega, Carmen

    2018-05-08

    Vaccination coverage for seasonal influenza and pneumococcus in rheumatology patients receiving biological treatment. To identify variables that predict vaccination adherence. Descriptive cross-sectional study. The study involved rheumatology patients who initiated biological therapy between 01/01/2016 and 12/31/2016 in a regional referral hospital. Variables included sociodemographic information, diagnostic data, treating physician, referral to the vaccine unit and vaccination against pneumococcus with 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), as well as seasonal influenza (2016/17). Univariate, bivariate (Chi-square) and multivariate analysis (logistic regression) were performed. The differences were considered significant (P<.05) and the PASW v.18 software package was used. In all, 222 patients were included. Vaccination coverage was: PCV13, 80.2%; PPSV23, 77.9%; influenza 2016/17, 78.8%; PCV13+PPSV23, 75.2%; PCV13+PPSV23+influenza 2016/17, 68.9%. Axial spondylitis had the highest coverage (>80%) for pneumococcal vaccination and combination of pneumococcal with influenza. Overall, 27% of the patients were not referred to the unit. The treating physician was associated with statistical significance in each vaccine alone or combined, but referral to the vaccine unit was independently associated with the highest vaccination coverage (P<.001) in all cases. Compared to the scientific literature, we consider that the coverage of our patients against pneumococcus and influenza is high. Referral of these patients to the vaccine unit is the key to guarantee a correct immunization and to minimize some of the possible infectious adverse effects of biological therapies. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Utilizing population variation, vaccination, and systems biology to study human immunology

    PubMed Central

    Tsang, John S.

    2016-01-01

    The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. PMID:26187853

  18. 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

  19. 76 FR 81467 - Availability of an Environmental Assessment for Field Testing Swine Influenza Vaccine, RNA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ...] Availability of an Environmental Assessment for Field Testing Swine Influenza Vaccine, RNA AGENCY: Animal and... Vaccine, RNA. The environmental assessment, which is based on a risk analysis prepared to assess the risks... veterinary biological product: Requester: Harrisvaccines, Inc. Product: Swine Influenza Vaccine, RNA. Field...

  20. Utilizing population variation, vaccination, and systems biology to study human immunology.

    PubMed

    Tsang, John S

    2015-08-01

    The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  1. Bioreactor concepts for cell culture-based viral vaccine production.

    PubMed

    Gallo-Ramírez, Lilí Esmeralda; Nikolay, Alexander; Genzel, Yvonne; Reichl, Udo

    2015-01-01

    Vaccine manufacturing processes are designed to meet present and upcoming challenges associated with a growing vaccine market and to include multi-use facilities offering a broad portfolio and faster reaction times in case of pandemics and emerging diseases. The final products, from whole viruses to recombinant viral proteins, are very diverse, making standard process strategies hardly universally applicable. Numerous factors such as cell substrate, virus strain or expression system, medium, cultivation system, cultivation method, and scale need consideration. Reviewing options for efficient and economical production of human vaccines, this paper discusses basic factors relevant for viral antigen production in mammalian cells, avian cells and insect cells. In addition, bioreactor concepts, including static systems, single-use systems, stirred tanks and packed-beds are addressed. On this basis, methods towards process intensification, in particular operational strategies, the use of perfusion systems for high product yields, and steps to establish continuous processes are introduced.

  2. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Vaccine stability study design and analysis to support product licensure.

    PubMed

    Schofield, Timothy L

    2009-11-01

    Stability evaluation supporting vaccine licensure includes studies of bulk intermediates as well as final container product. Long-term and accelerated studies are performed to support shelf life and to determine release limits for the vaccine. Vaccine shelf life is best determined utilizing a formal statistical evaluation outlined in the ICH guidelines, while minimum release is calculated to help assure adequate potency through handling and storage of the vaccine. In addition to supporting release potency determination, accelerated stability studies may be used to support a strategy to recalculate product expiry after an unintended temperature excursion such as a cold storage unit failure or mishandling during transport. Appropriate statistical evaluation of vaccine stability data promotes strategic stability study design, in order to reduce the uncertainty associated with the determination of the degradation rate, and the associated risk to the customer.

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

    PubMed

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

    2015-01-01

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

  5. Recent advances in the production of recombinant subunit vaccines in Pichia pastoris

    PubMed Central

    Wang, Man; Jiang, Shuai; Wang, Yefu

    2016-01-01

    ABSTRACT Recombinant protein subunit vaccines are formulated using defined protein antigens that can be produced in heterologous expression systems. The methylotrophic yeast Pichia pastoris has become an important host system for the production of recombinant subunit vaccines. Although many basic elements of P. pastoris expression system are now well developed, there is still room for further optimization of protein production. Codon bias, gene dosage, endoplasmic reticulum protein folding and culture condition are important considerations for improved production of recombinant vaccine antigens. Here we comment on current advances in the application of P. pastoris for the synthesis of recombinant subunit vaccines. PMID:27246656

  6. Application of new vaccine technology to improve immunity and productivity: advantages and challenges

    USDA-ARS?s Scientific Manuscript database

    Vaccines play a critical role in the poultry industry’s efforts to protect animals against disease. However, providing safe, efficacious, and cost-effective vaccines remains a constant concern to the industry. Recent advances in avian immunology, genetics, molecular biology, and pathogenesis have ...

  7. Biomedical applications of yeast- a patent view, part one: yeasts as workhorses for the production of therapeutics and vaccines.

    PubMed

    Roohvand, Farzin; Shokri, Mehdi; Abdollahpour-Alitappeh, Meghdad; Ehsani, Parastoo

    2017-08-01

    Yeasts, as Eukaryotes, offer unique features for ease of growth and genetic manipulation possibilities, making it an exceptional microbial host. Areas covered: This review provides general and patent-oriented insights into production of biopharmaceuticals by yeasts. Patents, wherever possible, were correlated to the original or review articles. The review describes applications of major GRAS (generally regarded as safe) yeasts for the production of therapeutic proteins and subunit vaccines; additionally, immunomodulatory properties of yeast cell wall components were reviewed for use of whole yeast cells as a new vaccine platform. The second part of the review will discuss yeast- humanization strategies and innovative applications. Expert opinion: Biomedical applications of yeasts were initiated by utilization of Saccharomyces cerevisiae, for production of leavened (fermented) products, and advanced to serve to produce biopharmaceuticals. Higher biomass production and expression/secretion yields, more similarity of glycosylation patterns to mammals and possibility of host-improvement strategies through application of synthetic biology might enhance selection of Pichia pastoris (instead of S. cerevisiae) as a host for production of biopharmaceutical in future. Immunomodulatory properties of yeast cell wall β-glucans and possibility of intracellular expression of heterologous pathogen/tumor antigens in yeast cells have expanded their application as a new platform, 'Whole Yeast Vaccines'.

  8. Vaccine production training to develop the workforce of foreign institutions supported by the BARDA influenza vaccine capacity building program.

    PubMed

    Tarbet, E Bart; Dorward, James T; Day, Craig W; Rashid, Kamal A

    2013-03-15

    In the event of an influenza pandemic, vaccination will be the best method to limit virus spread. However, lack of vaccine biomanufacturing capacity means there will not be enough vaccine for the world's population. The U.S. Department of Health and Human Services, Biomedical Advanced Research and Development Authority (BARDA) provides support to the World Health Organization to enhance global vaccine production capacity in developing countries. However, developing a trained workforce in some of those countries is necessary. Biomanufacturing is labor-intensive, requiring unique skills not found in traditional academic programs. Employees must understand the scientific basis of biotechnology, operate specialized equipment, and work in an environment regulated by good manufacturing practices (cGMP). Therefore, BARDA supported development of vaccine biomanufacturing training at Utah State University. The training consisted of a three-week industry-focused course for participants from institutions supported by the BARDA and WHO influenza vaccine production capacity building program. The curriculum was divided into six components: (1) biosafety, (2) cell culture and growth of cells in bioreactors, (3) virus assays and inactivation, (4) scale-up strategies, (5) downstream processing, and (6) egg- and cell-based vaccine production and cGMP. Lectures were combined with laboratory exercises to provide a balance of theory and hands-on training. The initial course included sixteen participants from seven countries including: Egypt, Romania, Russia, Serbia, South Korea, Thailand, and Vietnam. The participant's job responsibilities included: Production, Quality Control, Quality Assurance, and Research; and their education ranged from bachelors to doctoral level. Internal course evaluations utilized descriptive methods including surveys, observation of laboratory activities, and interviews with participants. Generally, participants had appropriate academic backgrounds, but

  9. Cancer vaccines inducing antibody production: more pros than cons.

    PubMed

    Jensen-Jarolim, Erika; Singer, Josef

    2011-09-01

    To date, passive immunotherapy with monoclonal antibodies is a well-established option in clinical oncology. By contrast, anticancer vaccines are less advanced, with the exception of successfully applied prophylactic vaccines against oncogenic virus infections. The creation of therapeutic vaccines is still a great challenge mostly due to the self-nature of tumor antigens. Therapeutic vaccines may be based on patient-specific material including pulsed effector cells, or tumor-associated antigens and derivatives thereof, such as peptides, mimotopes and nucleic acids. The latter represents a more universal approach, which would set an ideal economic framework resulting in broad patient access. In this article we focus on cancer vaccines for antibody production, in particular mimotope vaccines. The collected evidence suggests that they will open up new treatment options in minimal residual disease and early stage disease.

  10. Revaccination with Marek's Disease Vaccines Induces Productive Infection and Superior Immunity▿

    PubMed Central

    Wu, Changxin; Gan, Junji; Jin, Qiao; Chen, Chuangfu; Liang, Ping; Wu, Yantao; Liu, Xuefen; Ma, Li; Davison, Fred

    2009-01-01

    The most common lymphoproliferative disease in chickens is Marek's disease (MD), which is caused by the oncogenic herpesvirus Marek's disease virus (MDV). The emergence of hypervirulent pathotypes of MDV has led to vaccine failures, which have become common and which have resulted in serious economic losses in some countries, and a revaccination strategy has been introduced in practice. The mechanism by which revaccination invokes superior immunity against MD is unknown. After field trials which showed that revaccination provided protection superior to that provided by a single vaccination were performed, experiments were conducted to explore the interaction between revaccinated chickens and MDV. The results showed that the chickens in the revaccination groups experienced two consecutive productive infections but that the chickens in the single-vaccination groups experienced one productive infection, demonstrating that revaccination of viruses caused the chickens to have productive and then latent infections. Revaccination of the virus induced in the chickens a higher and a longer temporary expansion of the CD8+, CD4+, and CD3+ T-lymphocyte subpopulations, stronger peripheral blood lymphocyte proliferative activity; and higher levels of neutralizing antibody than single vaccination. These findings disagree with the postulate that MDV antigens persist, stimulate the immune system, and maintain a high level immunity after vaccination. The suppression of productive infection by maternal antibodies in chickens receiving the primary vaccination and a lower level of productive infection in the revaccination groups challenged with MDV were observed. The information obtained in this study suggests that the productive infection with revaccinated MDV in chickens plays a crucial role in the induction of superior immunity. This finding may be exploited for the development of a novel MD vaccine that results in the persistence of the antigen supply and that maintains a high

  11. [Animal experimentation in the discovery and production of veterinary vaccines].

    PubMed

    Audonnet, J Ch; Lechenet, J; Verschuere, B

    2007-08-01

    Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development.

  12. 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

  13. Agility in adversity: Vaccines on Demand.

    PubMed

    De Groot, Anne S; Moise, Leonard; Olive, David; Einck, Leo; Martin, William

    2016-09-01

    Is the US ready for a biological attack using Ebola virus or Anthrax? Will vaccine developers be able to produce a Zika virus vaccine, before the epidemic spreads around the world? A recent report by The Blue Ribbon Study Panel on Biodefense argues that the US is not ready for these challenges, however, technologies and capabilities that could address these deficiencies are within reach. Vaccine technologies have advanced and readiness has improved in recent years, due to advances in sequencing technology and computational power making the 'vaccines on demand' concept a reality. Building a robust strategy to design effective biodefense vaccines from genome sequences harvested by real-time biosurveillance will benefit from technologies that are being brought to bear on the cancer cure 'moonshot'. When combined with flexible vaccine production platforms, vaccines on demand will relegate expensive and, in some cases, insufficiently effective vaccine stockpiles to the dust heap of history.

  14. The Regulatory Evaluation of Vaccines for Human Use.

    PubMed

    Baylor, Norman W

    2016-01-01

    A vaccine is an immunogen, the administration of which is intended to stimulate the immune system to result in the prevention, amelioration, or therapy of any disease or infection (US Food and Drug Administration. Guidance for Industry: content and format of chemistry, manufacturing, and controls information and establishment description information for a vaccine or related product). A vaccine may be a live attenuated preparation of microorganisms, inactivated (killed) whole organisms, living irradiated cells, crude fractions, or purified immunogens, including those derived from recombinant DNA in a host cell, conjugates formed by covalent linkage of components, synthetic antigens, polynucleotides (such as the plasmid DNA vaccines), living vectored cells expressing specific heterologous immunogens, or cells pulsed with immunogen. Vaccines are highly complex products that differ from small molecule drugs because of the biological nature of the source materials such as those derived from microorganisms as well as the various cell substrates from which some are derived. Regardless of the technology used, because of their complexities, vaccines must undergo extensive characterization and testing. Special expertise and procedures are needed for their manufacture, control, and regulation. The Food and Drug Administration (FDA) is the National Regulatory Authority (NRA) in the United States responsible for assuring quality, safety, and effectiveness of all human medical products, including vaccines for human use.The Center for Biologics Evaluation and Research (CBER) within the US FDA is responsible for overseeing the regulation of therapeutic and preventative vaccines against infectious diseases. Authority for the regulation of vaccines resides in Section 351 of the Public Health Service Act and specific sections of the Federal Food, Drug, and Cosmetic Act (FD&C). Vaccines are regulated as biologics and licensed based on the demonstration of safety and effectiveness. The

  15. 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. Copyright 2014, SLACK Incorporated.

  16. Vaccination against histomonosis prevents a drop in egg production in layers following challenge.

    PubMed

    Liebhart, D; Sulejmanovic, T; Grafl, B; Tichy, A; Hess, M

    2013-02-01

    The effect of attenuated Histomonas meleagridis on pullets was investigated and the protection of vaccinated adult laying hens against a severe challenge was studied in the same experimental setting. Four groups of 25 pullets were set up at 18 weeks of life and birds in two groups were vaccinated with in vitro-attenuated H. meleagridis. Chickens in two groups (vaccinated and non-vaccinated) were challenged 5 weeks later with virulent histomonads, while the remaining groups were retained until termination of the study 11 weeks post vaccination. Vaccination of pullets did not have any impact on their subsequent performance. Egg production of non-vaccinated but challenged birds dropped significantly (P ≤ 0.05) between 2 and 4 weeks post challenge (p.c.) to 58.7%, compared with 90% in control chickens. At 4 weeks p.c., the drop in egg production in vaccinated and challenged birds was significantly lower (P=0.02) than in non-protected layers. Pathological changes were found only in challenged birds 2 and 6 weeks p.c. Several non-vaccinated birds showed severe lesions in the caeca with sporadic involvement of the liver and atrophy of the reproductive tract. Vaccination prior to challenge reduced the incidence of pathological findings. For the first time, vaccination of pullets with in vitro-attenuated histomonads could be shown to be an effective and safe prophylactic tool to prevent a severe drop in egg production of commercial layers following experimental infection.

  17. Rational design of vaccine targets and strategies for HIV: a crossroad of statistical physics, biology, and medicine.

    PubMed

    Chakraborty, Arup K; Barton, John P

    2017-03-01

    Vaccination has saved more lives than any other medical procedure. Pathogens have now evolved that have not succumbed to vaccination using the empirical paradigms pioneered by Pasteur and Jenner. Vaccine design strategies that are based on a mechanistic understanding of the pertinent immunology and virology are required to confront and eliminate these scourges. In this perspective, we describe just a few examples of work aimed to achieve this goal by bringing together approaches from statistical physics with biology and clinical research.

  18. Rational design of vaccine targets and strategies for HIV: a crossroad of statistical physics, biology, and medicine

    NASA Astrophysics Data System (ADS)

    Chakraborty, Arup K.; Barton, John P.

    2017-03-01

    Vaccination has saved more lives than any other medical procedure. Pathogens have now evolved that have not succumbed to vaccination using the empirical paradigms pioneered by Pasteur and Jenner. Vaccine design strategies that are based on a mechanistic understanding of the pertinent immunology and virology are required to confront and eliminate these scourges. In this perspective, we describe just a few examples of work aimed to achieve this goal by bringing together approaches from statistical physics with biology and clinical research.

  19. A Design of Experiment approach to predict product and process parameters for a spray dried influenza vaccine.

    PubMed

    Kanojia, Gaurav; Willems, Geert-Jan; Frijlink, Henderik W; Kersten, Gideon F A; Soema, Peter C; Amorij, Jean-Pierre

    2016-09-25

    Spray dried vaccine formulations might be an alternative to traditional lyophilized vaccines. Compared to lyophilization, spray drying is a fast and cheap process extensively used for drying biologicals. The current study provides an approach that utilizes Design of Experiments for spray drying process to stabilize whole inactivated influenza virus (WIV) vaccine. The approach included systematically screening and optimizing the spray drying process variables, determining the desired process parameters and predicting product quality parameters. The process parameters inlet air temperature, nozzle gas flow rate and feed flow rate and their effect on WIV vaccine powder characteristics such as particle size, residual moisture content (RMC) and powder yield were investigated. Vaccine powders with a broad range of physical characteristics (RMC 1.2-4.9%, particle size 2.4-8.5μm and powder yield 42-82%) were obtained. WIV showed no significant loss in antigenicity as revealed by hemagglutination test. Furthermore, descriptive models generated by DoE software could be used to determine and select (set) spray drying process parameter. This was used to generate a dried WIV powder with predefined (predicted) characteristics. Moreover, the spray dried vaccine powders retained their antigenic stability even after storage for 3 months at 60°C. The approach used here enabled the generation of a thermostable, antigenic WIV vaccine powder with desired physical characteristics that could be potentially used for pulmonary administration. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.

    PubMed

    Schiffer, Joshua T; Gottlieb, Sami L

    2017-09-25

    Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Transfer of technology for production of rabies vaccine: Memorandum from a WHO Meeting*

    PubMed Central

    1985-01-01

    The important challenge of prevention and control of rabies in the world will require international efforts to increase the availability and use of high quality cell-culture rabies vaccines for use in man and animals. An important aspect of activities to ensure such availability is transfer of technologies to developing countries for production of these vaccines. This article, which is based on the report of a WHO Consultation, outlines the technical options for vaccine production. The principles and economic aspects of technology transfer are considered, and a WHO assistance programme is outlined. It is concluded that technology transfer should be mediated through a framework of national institutes, expert panels, WHO collaborating centres, production and control laboratories, and other relevant institutions. On this basis, recommendations are made concerning the mechanisms of technology transfer for production of cell-culture rabies vaccines. PMID:3878738

  2. Now that you want to take your HIV/AIDS vaccine/biological product research concept into the clinic: what are the "cGMP"?

    PubMed

    Sheets, Rebecca L; Rangavajhula, Vijaya; Pullen, Jeffrey K; Butler, Chris; Mehra, Vijay; Shapiro, Stuart; Pensiero, Michael

    2015-04-08

    The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of "cGMP" and know that they are supposed to make a "GMP product" to take into the clinic, but often they are not very familiar with what "cGMP" means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked "can't we use the material we made in the lab in the clinic?" or "aren't Phase 1 studies exempt from cGMP?" Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. Published by Elsevier Ltd.

  3. FDA 101: Regulating Biological Products

    MedlinePlus

    ... Home For Consumers Consumer Updates FDA 101: Regulating Biological Products Share Tweet Linkedin Pin it More sharing ... about this diverse and highly important field. What biological products does FDA regulate? The Center for Biologics ...

  4. Heterologous vaccine effects.

    PubMed

    Saadatian-Elahi, Mitra; Aaby, Peter; Shann, Frank; Netea, Mihai G; Levy, Ofer; Louis, Jacques; Picot, Valentina; Greenberg, Michael; Warren, William

    2016-07-25

    The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological studies and are increasingly recognized as an important biological process by a growing group of immunologists and epidemiologists. Much remain to be learned about the extent and underlying mechanisms for these effects. The conference "Off-target effects of vaccination" held in Annecy-France (June 8-10 2015) intended to take a holistic approach drawing from the fields of immunology, systems biology, epidemiology, bioinformatics, public health and regulatory science to address fundamental questions of immunological mechanisms, as well as translational questions about vaccines NSEs. NSE observations were examined using case-studies on live attenuated vaccines and non-live vaccines followed by discussion of studies of possible biological mechanisms. Some possible pathways forward in the study of vaccines NSE were identified and discussed by the expert group. Copyright © 2016.

  5. Hib Vaccines: Past, Present, and Future Perspectives

    PubMed Central

    Zarei, Adi Essam; Almehdar, Hussein A.; Redwan, Elrashdy M.

    2016-01-01

    Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5–10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy. PMID:26904695

  6. Vaccines for Pandemic Influenza

    PubMed Central

    Luke, Catherine J.

    2006-01-01

    Recent outbreaks of highly pathogenic avian influenza in Asia and associated human infections have led to a heightened level of awareness and preparation for a possible influenza pandemic. Vaccination is the best option by which spread of a pandemic virus could be prevented and severity of disease reduced. Production of live attenuated and inactivated vaccine seed viruses against avian influenza viruses, which have the potential to cause pandemics, and their testing in preclinical studies and clinical trials will establish the principles and ensure manufacturing experience that will be critical in the event of the emergence of such a virus into the human population. Studies of such vaccines will also add to our understanding of the biology of avian influenza viruses and their behavior in mammalian hosts. PMID:16494720

  7. [Incidence of biological accidents at work and immune status for vaccine-preventable diseases among resident physicians in specialist training at Ferrara University Hospital].

    PubMed

    Stefanati, Armando; Brosio, Federica; Kuhdari, Parvanè; Baccello, Valeria; De Paris, Paola; Nardini, Marco; Boschetto, Piera; Lupi, Silvia; Gabutti, Giovanni

    2017-01-01

    The hospital as a work environment is particularly characterized by various risks for healthcare workers (HCWs). The main risk is represented by biological accidents, associated with the parenteral transmission of pathogens. Biological injuries can occur during the care service and the manipulation of biological fluids. Hepatitis B (and hepatitis D), hepatitis C and HIV are the most common infections transmitted by biological injuries. Physicians should acquire awareness of the risks associated with their professional activity during their training as medical residents (MRs). Some infectious diseases are preventable by vaccination and the "National Immunization Plan 2017-2019" (PNPV) recommends HCWs vaccination against hepatitis B, influenza, measles -mumps -rubella, chicken pox, and pertussis. Besides, not only HCWs' vaccination can prevent the disease in healthcare professionals, but it also may reduce the transmission to patients. Therefore, active immunization of HCWs by recommended vaccinations plays an important role to prevent disease cases, complications and death in patients. An increased awareness of risk behaviors is the first important point to address in order to reduce biological accidents and infectious diseases transmission, so as to reduce their frequency. Besides, HCWs' vaccination is useful to reinforce protection and to prevent the transmission of some infectious diseases in case of exposure. The aim of this five-year incidence study is to investigate the MRs' biological accidents characteristics and to analyze the MRs' immune status at the University of Ferrara in the period 2011-2015. Data on MRs' biological accidents and immune status at Azienda Ospedaliero-Universitaria of Ferrara in 2011-2015 were analyzed by Microsoft Excel 2007 Software. In this study, the percentage of MRs' biological injuries compared to the total number of MRs showed an annual variability, with a peak in 2011 (11.9%). During the analyzed period, there were 190

  8. [Development of new vaccines].

    PubMed

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

    Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.

  9. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Mixing biological products. 114.6... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form, shall be mixed thoroughly in a single container. During bottling operations, the product shall be...

  10. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Mixing biological products. 114.6... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form, shall be mixed thoroughly in a single container. During bottling operations, the product shall be...

  11. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Mixing biological products. 114.6... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form, shall be mixed thoroughly in a single container. During bottling operations, the product shall be...

  12. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Mixing biological products. 114.6... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form, shall be mixed thoroughly in a single container. During bottling operations, the product shall be...

  13. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mixing biological products. 114.6... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form, shall be mixed thoroughly in a single container. During bottling operations, the product shall be...

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

    PubMed

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

    2011-04-01

    Safety 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. The 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 IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded. Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%). Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

  15. Duration of immunity for canine and feline vaccines: a review.

    PubMed

    Schultz, Ronald D

    2006-10-05

    In our studies aimed at assessing the minimum duration of vaccinal immunity (DOI), approximately 1000 dogs have been vaccinated with products from all the major US veterinary biological companies. The DOI for the various products is determined by antibody titers for all dogs and, by challenge studies in selected groups of dogs. Recently, all major companies that make canine vaccines for the U.S. market have completed their own studies; published data show a 3 years or longer minimum DOI for the canine core products, canine distemper virus (CDV), canine parvovirus type 2 (CPV-2), and canine adenovirus-2 (CAV-2). Studies with feline core vaccines - feline parvovirus (FPV), calicivirus (FCV) and herpes virus type I (FHV-1) have shown a minimum DOI of greater than 3 years. Based on these results, the current canine and feline guidelines (which recommend that the last dose of core vaccines be given to puppies and kittens > or =12 weeks of age or older, then revaccination again at 1 year, then not more often than every 3 years) should provide a level of protection equal to that achieved by annual revaccination. In contrast, the non-core canine and feline vaccines, perhaps with the exception of feline leukaemia vaccines, provide immunity for < or =1 year. In general the effectiveness of the non-core products is less than the core products. Thus, when required, non-core vaccines should be administered yearly, or even more frequently.

  16. Biological characteristics of genetic variants of Urabe AM9 mumps vaccine virus.

    PubMed

    Wright, K E; Dimock, K; Brown, E G

    2000-03-01

    The Urabe AM9 mumps vaccine is composed of a mixture of variants distinguishable by a difference at nucleotide (nt) 1081 of the hemagglutinin-neuraminidase (HN) gene (Brown, E.G., Dimock, K., Wright, K.E., 1996. The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid (aa) 335 of the hemagglutinin-neuraminidase gene with one form associated with disease. J. Infect. Dis. 174, 619-622.). Further genetic and biological variation was detected in plaque purified viruses from the Urabe AM9 vaccine by examining the HN gene sequence, plaque morphology, cytopathic effects and growth in Vero cells, and temperature sensitivity (ts). Infection of Vero cells with plaque purified viruses with a G at nt 1081 of the HN gene produced large, clear plaques, caused significant CPE early after infection but yielded lower titres of virus than other purified viruses. None of these viruses were ts. In contrast, half of the plaque purified viruses with an A at nt 1081 were sensitive to a temperature of 39.5 degrees C. These viruses produced small plaques, caused significant CPE and grew to low titres. Two ts viruses possessed a unique aa substitution at aa 468 of HN. The remaining A(1081) viruses were not ts, produced large plaques but little CPE, and grew to titres 10-fold higher than the G(1081) viruses. Isolates of Urabe AM9 associated with post-vaccination illness were similar to these non-ts A(1081) viruses, but could be further sub-divided into two groups on the basis of a difference at aa 464 of HN. The post-vaccination isolates may represent insufficiently attenuated components of the vaccine, while the G(1081) and ts subset of A(1081) viruses may be more fully attenuated.

  17. Design of clinical trials for therapeutic cancer vaccines development.

    PubMed

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    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. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  18. 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

  19. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Identification of biological products... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.4 Identification of biological products. Suitable tags or labels of... biological products, all component parts to be combined to form a biological product, all biological products...

  20. Pre-vaccination nasopharyngeal pneumococcal carriage in a Nigerian population: epidemiology and population biology.

    PubMed

    Adetifa, Ifedayo M O; Antonio, Martin; Okoromah, Christy A N; Ebruke, Chinelo; Inem, Victor; Nsekpong, David; Bojang, Abdoulie; Adegbola, Richard A

    2012-01-01

    Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria. This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST). The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage. Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for

  1. [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.

  2. On the optimal production capacity for influenza vaccine.

    PubMed

    Forslid, Rikard; Herzing, Mathias

    2015-06-01

    This paper analyzes the profit maximizing capacity choice of a monopolistic vaccine producer facing the uncertain event of a pandemic in a homogenous population of forward-looking individuals. For any capacity level, the monopolist solves the intertemporal price discrimination problem within the dynamic setting generated by the standard mathematical epidemiological model of infectious diseases. Even though consumers are assumed to be identical, the monopolist will be able to exploit the ex post heterogeneity between infected and susceptible individuals by raising the price of vaccine in response to the increasing hazard rate. The monopolist thus bases its investment decision on the expected profits from the optimal price path given the infection dynamics. It is shown that the monopolist will always choose to invest in a lower production capacity than the social planner. Through numerical simulation, it is demonstrated how the loss to society of having a monopoly producer decreases with the speed of infection transmission. Moreover, it is illustrated how the monopolist's optimal vaccination rate increases as its discount rate rises for cost parameters based on Swedish data. However, the effect of the firm discount rate on its investment decision is sensitive to assumptions regarding the cost of production capacity. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Tobacco derived cancer vaccines for non-Hodgkin's lymphoma: perspectives and progress.

    PubMed

    McCormick, Alison A

    2011-03-01

    Everyone appreciates the irony of using tobacco plants to cure cancer. (1) Recently featured in a populist Wall Street Journal article, (2) the use of plants to produce medicinal products was presented as novel, even though we are decades into development of numerous products for specific medical applications (reviewed extensively in (3, 4)). Though the tobacco plant and its relatives offer a qualified set of advantages for producing complex biologicals, and in many cases overcome problems that plague traditional expression systems, FDA licensed products derived from bioengineered plants have yet to appear in the marketplace. Despite a difficult beginning, recent advances in plant biotechnology have been as cutting edge as those in the fields of molecular biology and chemical engineering, which now position the field for a new level of commercial relevance. The basis for this review is a description of the first FDA qualified parenterally administered vaccine clinical trial using a plant derived product. We have confirmed in this trial that plant proteins can be qualified to the same level as biologicals from other sources, and are safe when given as injected vaccines. Most importantly though, immune responses to plant proteins were seen in 66% of cancer patients, and these responses were to the desired antigenic determinants, not to xenogenic plant antigens. Problems and solutions that arose during the development of a safe and effective human vaccine are discussed.

  4. Vaccine manufacturing and technology: from biotechnological platforms to syntethic epitopes, current viepoint.

    PubMed

    Ignateva, G A

    2016-01-01

    The Purposes: the review take into account short history of vaccination practice and development of vaccine technology. In the review we include data from several monographs about manufacturing of vaccines published by authors from such companies as Merck & Co; Sanofi Pasteur; Dynavax Europe/Rhein Biotech GmbH; Latham Biopharm Group; Aridis Pharmaceuticals LLC; Genentech; Amgen; Shamir Biologics LLC; Biopharm Services US; Novartis Pharma AG, аnd several research centers: Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research; Purdue University, West Lafayette, IN, US; Department of Pharmaceutical Chemistry, Univ. Of Kansas; Max Planck Institute for dynamics of Complex Technical Systems; Fraunhofer USA Center for Molecular Biotechnology; US Dep. of Agriculture Animal and Plant Health Inspection Service, etc. In historic literature there are data about inoculation practices in antique China, Persia, India, Byzantium, native Americans, some African population. In modern immunology since the end of XIX century the vaccines were produced at the in vivo platforms - in animals (rabbits, mice, cows). Since 1931 due to E. Goodpasture' elaboration most virus vaccines were and are produced at the in ovo platform. In 1949 J.F. Enders elaborated large-scale polio virus production in the primary culture of monkey kidney cells in vitro. Up to day primary culture of chiken embrio fibroblasts are used to large-scale production of vaccine viruses of measles, mumps, rabies. Since 2000-th in Western countries most part of virus vaccines were began to produced via a cultivation in continuous tumor cell lines. The last technology is the most low cost for large-scale production of vaccines. We review several new biotechnological platforms for the production of the recombinant protein or virus-like particles as subunit vaccines: plant system, algae, mushrooms, insect cells, etc. Beside of good purpose of vaccination - prophylactic of several infectious

  5. Adjuvant solution for pandemic influenza vaccine production.

    PubMed

    Clegg, Christopher H; Roque, Richard; Van Hoeven, Neal; Perrone, Lucy; Baldwin, Susan L; Rininger, Joseph A; Bowen, Richard A; Reed, Steven G

    2012-10-23

    Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.

  6. Biological and Phylogenetic Characterization of a Genotype VII Newcastle Disease Virus from Venezuela: Efficacy of Field Vaccination

    PubMed Central

    Perozo, Francisco; Marcano, Rosmar

    2012-01-01

    Here we report the biological and molecular characterization of a virulent genotype VII Newcastle disease virus (NDV) circulating in Venezuela and the assessment of the vaccination efficacy under field conditions compared to controlled rearing conditions. Biological pathotyping showed a mean embryo dead time of 50 h and an intracerebral pathogenicity index of 1.86. Sequence-based phylogenetic analysis demonstrated that the virus belongs to genotype VII in class II (a genotype often found in Asia and Africa), representing the first report of the presence of this genotype in the continent of South America. A vaccine-challenge trial in commercial broilers reared in fields or in a experimental setting included dual (live/killed) priming of 1-day-old chicks plus two live NDV and infectious bursal disease virus (IBDV) field vaccinations at days 7 and 17, followed by a very stringent genotype VII NDV challenge at day 28. Serology for NDV and IBDV, bursal integrity, and protection against NDV lethal challenge were assessed. At 28 days, field vaccinates showed significantly lower NDV (1,356 versus 2,384) and higher IBD (7,295 versus 1,489) enzyme-linked immunosorbent assay (ELISA) antibody titers than the experimentally reared birds. A lower bursal size and bursa-body weight ratio (P < 0.05) and higher bursa lesion score were also detected in the field set. Only 57.1% of field vaccinates survived the lethal challenge, differing (P < 0.05) from 90.5% survival in the experimental farm. Overall, results confirmed the presence of the genotype VII viruses in South America and suggest that field-associated factors such as immunosuppression compromise the efficacy of the vaccination protocols implemented. PMID:22238433

  7. Production of adenovirus vectors and their use as a delivery system for influenza vaccines

    PubMed Central

    Vemula, Sai V.; Mittal, Suresh K.

    2010-01-01

    IMPORTANCE OF THE FIELD With the emergence of highly pathogenic avian influenza H5N1 viruses that have crossed species barriers and are responsible for lethal infections in humans in many countries, there is an urgent need for the development of effective vaccines which can be produced in large quantities at a short notice and confer broad protection against these H5N1 variants. In order to meet the potential global vaccine demand in a pandemic scenario, new vaccine-production strategies must be explored in addition to the currently used egg-based technology for seasonal influenza. AREAS COVERED IN THIS REVIEW Adenovirus (Ad) based influenza vaccines represent an attractive alternative/supplement to the currently licensed egg-based influenza vaccines. Ad-based vaccines are relatively inexpensive to manufacture, and their production process does not require either chicken eggs or labor intensive and time-consuming processes necessitating enhanced biosafety facilities. Most importantly, in a pandemic situation, this vaccine strategy could offer a stockpiling option to reduce the response time before a strain-matched vaccine could be developed. WHAT THE READER WILL GAIN This review discusses Ad-vector technology and the current progress in the development of Ad-based influenza vaccines. TAKE HOME MESSAGE Ad vector-based influenza vaccines for pandemic preparedness are under development to meet the global vaccine demand. PMID:20822477

  8. History of vaccination.

    PubMed

    Plotkin, Stanley

    2014-08-26

    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.

  9. Role of parasitic vaccines in integrated control of parasitic diseases in livestock

    PubMed Central

    Sharma, Neelu; Singh, Veer; Shyma, K. P.

    2015-01-01

    Parasitic infections adversely affect animal’s health and threaten profitable animal production, thus affecting the economy of our country. These infections also play a major role in the spread of zoonotic diseases. Parasitic infections cause severe morbidity and mortality in animals especially those affecting the gastrointestinal system and thus affect the economy of livestock owner by decreasing the ability of the farmer to produce economically useful animal products. Due to all these reasons proper control of parasitic infection is critically important for sustained animal production. The most common and regularly used method to control parasitic infection is chemotherapy, which is very effective but has several disadvantages like drug resistance and drug residues. Integrated approaches to control parasitic infections should be formulated including grazing management, biological control, genetic resistance of hosts, and parasitic vaccines. India ranks first in cattle and buffalo population, but the majority of livestock owners have fewer herds, so other measures like grazing management, biological control, genetic resistance of hosts are not much practical to use. The most sustainable and economical approach to control parasitic infection in our country is to vaccinate animals, although vaccines increase the initial cost, but the immunity offered by the vaccine are long lived. Thus, vaccination of animals for various clinical, chronic, subclinical parasitic infections will be a cheaper and effective alternative to control parasitic infection for long time and improve animal production. PMID:27047140

  10. Egg-Independent Influenza Vaccines and Vaccine Candidates

    PubMed Central

    Manini, Ilaria; Pozzi, Teresa; Rossi, Stefania; Montomoli, Emanuele

    2017-01-01

    Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines. PMID:28718786

  11. 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. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

  12. 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.

  13. Plant-derived virus-like particles as vaccines

    PubMed Central

    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

  14. Live attenuated tetravalent dengue vaccine.

    PubMed

    Bhamarapravati, N; Sutee, Y

    2000-05-26

    The development of a live attenuated tetravalent dengue vaccine is currently the best strategy to obtain a vaccine against dengue viruses. The Mahidol University group developed candidate live attenuated vaccines by attenuation through serial passages in certified primary cell cultures. Dengue serotype 1, 2 and 4 viruses were developed in primary dog kidney cells, whereas dengue serotype 3 was serially passaged in primary African green monkey kidney cells. Tissue culture passaged strain viruses were subjected to biological marker studies. Candidate vaccines have been tested as monovalent (single virus), bivalent (two viruses), trivalent (three viruses) and tetravalent (all four serotype viruses) vaccines in Thai volunteers. They were found to be safe and immunogenic in both adults and children. The Mahidol live attenuated dengue 2 virus was also tested in American volunteers and resulted in good immune response indistinguishable from those induced in Thai volunteers. The master seeds from the four live attenuated virus strains developed were provided to Pasteur Merieux Connaught of France for production on an industrial scale following good manufacturing practice guidelines.

  15. Protocol for the Production of a Vaccine Against Argentinian Hemorrhagic Fever.

    PubMed

    Ambrosio, Ana María; Mariani, Mauricio Andrés; Maiza, Andrea Soledad; Gamboa, Graciela Susana; Fossa, Sebastián Edgardo; Bottale, Alejando Javier

    2018-01-01

    Argentinian hemorrhagic Fever (AHF) is a febrile, acute disease caused by Junín virus (JUNV), a member of the Arenaviridae. Different approaches to obtain an effective antigen to prevent AHF using complete live or inactivated virus, as well as molecular constructs, have reached diverse development stages. This chapter refers to JUNV live attenuated vaccine strain Candid #1, currently used in Argentina to prevent AHF. A general standardized protocol used at Instituto Nacional de Enfermedades Virales Humanas (Pergamino, Pcia. Buenos Aires, Argentina) to manufacture the tissue culture derived Candid #1 vaccine is described. Intermediate stages like viral seeds and cell culture bank management, bulk vaccine manufacture, and finished product processing are also separately presented in terms of Production and Quality Control/Quality Assurance requirements, under the Adminitracion Nacional de Medicamentos, Alimentos y Tecnología Medica (ANMAT), the Argentine national regulatory authority.

  16. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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 Biological products... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Biological products; exemption. 106.1...

  17. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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 Biological products... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Biological products; exemption. 106.1...

  18. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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 Biological products... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Biological products; exemption. 106.1...

  19. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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 Biological products... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products; exemption. 106.1...

  20. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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 Biological products... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Biological products; exemption. 106.1...

  1. Synthetic Biology for Therapeutic Applications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

  2. Synthetic Biology for Therapeutic Applications

    DOE PAGES

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    2014-08-06

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  4. Vaccines 'on demand': science fiction or a future reality.

    PubMed

    Ulmer, Jeffrey B; Mansoura, Monique K; Geall, Andrew J

    2015-02-01

    Self-amplifying mRNA vaccines are being developed as a platform technology with potential to be used for a broad range of targets. The synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. Preclinical proof of concept has so far been achieved for influenza, respiratory syncytial virus, rabies, Ebola, cytomegalovirus, human immunodeficiency virus and malaria. This editorial highlights the key milestones in the discovery and development of self-amplifying mRNA vaccines, and reviews how they might be used as a rapid response platform. The paper points out how future improvements in RNA vector design and non-viral delivery may lead to decreases in effective dose and increases in production capacity. The prospects for non-viral delivery of self-amplifying mRNA vaccines are very promising. Like other types of nucleic acid vaccines, these vaccines have the potential to draw on the positive attributes of live-attenuated vaccines while obviating many potential safety limitations. Hence, this approach could enable the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats.

  5. Whither vaccines?

    PubMed

    Rodrigues, Charlene M C; Pinto, Marta V; Sadarangani, Manish; Plotkin, Stanley A

    2017-06-01

    Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  6. Evaluation of some selected vaccines and other biological products irradiated by gamma rays, electron beams and X-rays

    NASA Astrophysics Data System (ADS)

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

    2002-03-01

    Molecular sizing potency results are presented for irradiated samples of one lot of Haemophilus b conjugate vaccine, pneumococcal polysaccharide type 6B and typhoid vi polysaccharide vaccine. The samples were irradiated (25 kGy) by gamma rays, electron beams and X-rays. IgG and IgM antibody response in mice test results (ELISA) are given for the Hib conjugate vaccine irradiated at 0°C or frozen in liquid nitrogen.

  7. Antiradiation Vaccine: Technology Development Of Prophylaxis, Prevention And Treatment Of Biological Consequences And Complications After Neutron Irradiation.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    Introduction: Neutrons irradiation produce a unique biological effectiveness compare to different types of radiation because their ability to create a denser trail of ionized atoms in biological living tissues[Straume 1982; Latif et al.2010; Katz 1978; Bogatyrev 1982]. The efficacy of an Anti-Radiation Vaccine for the prophylaxis, prevention and therapy of acute radiation pathology was studied in a neutron exposure facility. The biological effects of fast neutrons include damage of central nervous system and cardiovascular system with development of Acute Cerebrovascular and Cardiovascular forms of acute radiation pathology. After irradiation by high doses of fast neutron, formation of neurotoxins, hematotoxins,cytotoxins forming from cell's or tissue structures. High doses of Neutron Irradiation generate general and specific toxicity, inflammation reactions. Current Acute Medical Management and Methods of Radiation Protection are not effective against moderate and high doses of neutron irradiation. Our experiments demonstrate that Antiradiation Vaccine is the most effective radioprotectant against high doses of neutron-radiation. Radiation Toxins(biological substances with radio-mimetic properties) isolated from central lymph of gamma-irradiated animals could be working substance with specific antigenic properties for vaccination against neutron irradiation. Methods: Antiradiation Vaccine preparation standard - mixture of a toxoid form of Radiation Toxins - include Cerebrovascular RT Neurotoxin, Cardiovascular RT Neurotoxin, Gastrointestinal RT Neurotoxin, Hematopoietic RT Hematotoxin. Radiation Toxins were isolated from the central lymph of gamma-irradiated animals with different forms of Acute Radiation Syndromes - Cerebrovascular, Cardiovascular, Gastrointestinal, Hematopoietic forms. Devices for Y-radiation were "Panorama","Puma". Neutron exposure was accomplished at the Department of Research Institute of Nuclear Physics, Dubna, Russia. The neutrons

  8. Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives.

    PubMed

    Sala, Francesco; Manuela Rigano, M; Barbante, Alessandra; Basso, Barbara; Walmsley, Amanda M; Castiglione, Stefano

    2003-01-30

    Stable integration of a gene into the plant nuclear or chloroplast genome can transform higher plants (e.g. tobacco, potato, tomato, banana) into bioreactors for the production of subunit vaccines for oral or parental administration. This can also be achieved by using recombinant plant viruses as transient expression vectors in infected plants. The use of plant-derived vaccines may overcome some of the major problems encountered with traditional vaccination against infectious diseases, autoimmune diseases and tumours. They also offer a convenient tool against the threat of bio-terrorism. State of the art, experimental strategies, safety and perspectives are discussed in this article.

  9. Pre-Vaccination Nasopharyngeal Pneumococcal Carriage in a Nigerian Population: Epidemiology and Population Biology

    PubMed Central

    Adetifa, Ifedayo M. O.; Antonio, Martin; Okoromah, Christy A. N.; Ebruke, Chinelo; Inem, Victor; Nsekpong, David; Bojang, Abdoulie; Adegbola, Richard A.

    2012-01-01

    Background Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria. Methods This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST). Results The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage. Conclusions Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our

  10. Synthetic Biology for Therapeutic Applications

    PubMed Central

    2015-01-01

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders. PMID:25098838

  11. Establishment of a biological reference preparation for hepatitis A vaccine (inactivated, non-adsorbed).

    PubMed

    Stalder, J; Costanzo, A; Daas, A; Rautmann, G; Buchheit, K-H

    2010-04-01

    A reference standard calibrated in International Units (IU) is needed for the in vitro potency assay of hepatitis A vaccines prepared by formalin-inactivation of purified hepatitis A virus grown in cell cultures. Thus, a project was launched by the European Directorate for the Quality of Medicines & HealthCare (EDQM) to establish one or more non-adsorbed inactivated hepatitis A vaccine reference preparation(s) as working standard(s), calibrated against the 1st International Standard (IS), for the in vitro potency assay (ELISA) of all vaccines present on the European market. Four non-adsorbed liquid preparations of formalin-inactivated hepatitis A antigen with a known antigen content were obtained from 3 manufacturers as candidate Biological Reference Preparations (BRPs). Thirteen laboratories participated in the collaborative study. They were asked to use an in vitro ELISA method adapted from a commercially available kit for the detection of antibodies to hepatitis A virus. In-house validated assays were to be run in parallel, where available. Some participants also included commercially available hepatitis A vaccines in the assays, after appropriate desorption. During the collaborative study, several participants using the standard method were faced with problems with some of the most recent lots of the test kits. Due to these problems, the standard method did not perform satisfactorily and a high number of assays were invalid, whereas the in-house methods appeared to perform better. Despite this, the overall mean results of the valid assays using both methods were in agreement. Nonetheless, it was decided to base the assignment of the potency values on the in-house methods only. The results showed that all candidate BRPs were suitable for the intended purpose. However, based on availability of the material and on the results of end-product testing, 2 candidate reference preparations, Samples C and D, were selected. Both were from the same batch but filled on

  12. Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

    PubMed

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-03

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

  13. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Impact of fowlpox-vectored Mycoplasma gallisepticum vaccine Vectormune FP MG on layer hen egg production and egg quality parameters.

    PubMed

    Leigh, S A; Branton, S L; Evans, J D; Collier, S D

    2013-12-01

    This study was conducted to determine the impact of vaccination with Vectormune FP MG on egg production and egg quality characteristics of Single Comb White Leghorn hens. Due to questions of the efficacy of this vaccine in preventing Mycoplasma gallisepticum-mediated pathology, the ability of this vaccine to protect against postproduction-peak egg losses associated with F-strain M. gallisepticum (FMG) vaccination was also investigated. Vaccination with Vectormune FP MG did not result in any significant change in egg production or egg quality parameters compared with control (unvaccinated) hens. Subsequent revaccination with FMG at 45 wk of age (woa) yielded no impact on egg production or egg quality parameters of Vectormune FP MG vaccinated hens, unlike prior results for postproduction-peak vaccination of M. gallisepticum-clean hens with FMG, which exhibited a drop in egg production of approximately 6%. No difference in egg size distribution was observed for any of the treatment groups before or after FMG revaccination. These results suggest that hens can be safely vaccinated with Vectormune FP MG as pullets and can be revaccinated with a live M. gallisepticum vaccine such as FMG at a later date with no deleterious effects on egg production or egg or eggshell quality parameters.

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

    PubMed

    Gołoś, Aleksandra; Lutyńska, Anna

    2015-01-01

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

  16. Human vaccines & immunotherapeutics: news.

    PubMed

    Riedmann, Eva M

    2013-07-01

    Recent advances in the development of immunotherapeutic mAbs for cancer New vaccine reduces malaria infection by 72% Bavarian Nordic's cancer immunotherapy shows promise in colorectal cancer Chinese HFMD vaccine shows high efficacy in Phase 3 Two-dose regimen of Merck's Gardasil looks effective Accelerating influenza vaccine development using synthetic biology A key role for gut microbes in vaccination Understanding of and attitudes towards vaccines: a study in teenagers.

  17. Characterization of Inherent Particles and Mechanism of Thermal Stress Induced Particle Formation in HSV-2 Viral Vaccine Candidate.

    PubMed

    Li, Lillian; Kirkitadze, Marina; Bhandal, Kamaljit; Roque, Cristopher; Yang, Eric; Carpick, Bruce; Rahman, Nausheen

    2017-11-10

    Vaccine formulations may contain visible and/or subvisible particles, which can vary in both size and morphology. Extrinsic particles, which are particles not part of the product such as foreign contaminants, are generally considered undesirable and should be eliminated or controlled in injectable products. However, biological products, in particular vaccines, may also contain particles that are inherent to the product. Here we focus on the characterization of visible and subvisible particles in a live, replication-deficient viral vaccine candidate against HSV genital herpes in an early developmental stage. HSV-2 viral vaccine was characterized using a panel of analytical methods, including Fourier transform infrared spectroscopy (FTIR), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, liquid chromatography-mass spectrometry (LC-MS), light microscopy, transmission electron microscopy (TEM), micro-flow imaging (MFI), dynamic light scattering (DLS), right angle light scattering (RALS), and intrinsic fluorescence. Particles in HSV-2 vaccine typically ranged from hundreds of nanometers to hundreds of micrometers in size and were determined to be inherent to the product. The infectious titer did not correlate with any trend in subvisible particle concentration and size distribution as shown by DLS, MFI, and TEM under stressed conditions. This suggested that particle changes in the submicron range were related to HSV-2 virion structure and had direct impact on biological activity. It was also observed that subvisible and visible particles could induce aggregation in the viral product. The temperature induced aggregation was observed by RALS, intrinsic fluorescence, and DLS. The increase of subvisible particle size with temperature could be fitted to a two-step thermokinetic model. Visible and subvisible particles were found to be inherent to the HSV-2 viral vaccine product. The mechanism of protein aggregation was discussed and a two

  18. Reduced egg production in hens associated with avian influenza vaccines and formalin levels.

    PubMed

    Meng, Di; Hui, Zhang; Yang, Jianming; Yuan, Jilei; Ling, Yong; He, Cheng

    2009-03-01

    A rapid drop in egg production and a high culling rate in hens are associated with using four avian influenza (AI) inactivated vaccines. Average formalin levels in 22 batches of commercial AI vaccines are 0.34%, 0.59%, 0.79%, and 0.33%, respectively, in H5N1 Re-1, Re-4, Re-1+Re-4, and Re-1+H9N2 vaccines. Laying production rate dropped from the expected 96.1% to 68.3%, 62.6%, and 54.1%, respectively, in hens that received H5N1 Re-1 strain, Re-4 strain, or Re-1+Re-4 strain vaccines, and the culling rate was 8.8%, 15.0%, and 18.0%, respectively. AI vaccines containing 0.66%-0.81% formalin could significantly induce lower estradiol levels and decreased antibody titers of H5 subtype in a field study. In an experimental study, 200 16-wk-old laying hens were randomly divided into four groups and intramuscularly injected 0.5 ml per chicken formalin-oil preparation at the dose of 0.10%, 0.40%, and 0.81% formalin, respectively. The control hens were given 0.5 ml phosphate buffered saline. Egg performance and degenerative combs were examined daily. The results showed that 0.81% formalin preparation significantly induced an egg production drop and lower estradiol levels as compared to the lower formalin preparations. Significant degeneration of combs and ovarian follicles was also observed. These changes suggest that vaccines with more than the recommended formalin concentration lower hemaglutination inhibition antibody levels and induce an imbalance in estradiol secretion, resulting in degenerative change in ovarian follicles and uterus. Hence, new H5N1 vaccines with recommended formalin levels are urgently needed.

  19. Development and approval of vaccines in the United States.

    PubMed

    Botstein, P

    1986-01-01

    In the United States, vaccines and the establishments in which they are manufactured are required to be licensed by the Food and Drug Administration (FDA) before the vaccine can be marketed. This licensing process, as well as the development and investigation of vaccines, is regulated by the FDA's Office of Biologics Research and Review. An application for licensing must contain information supporting the safety, effectiveness, purity and potency of the product. These are data obtained during the investigational phase and then submitted by a commercial sponsor for review and approval. Inspections, surveillance and laboratory testing are performed by the FDA before and after issuance of a license for marketing. The procedures and policies in the investigational and licensing phases of vaccine development are described.

  20. Enhancing enterovirus A71 vaccine production yield by microcarrier profusion bioreactor culture.

    PubMed

    Liu, Chia-Chyi; Wu, Suh-Chin; Wu, Shang-Rung; Lin, Hsiao-Yu; Guo, Meng-Shin; Yung-Chih Hu, Alan; Chow, Yen-Hung; Chiang, Jen-Ron; Shieh, Dar-Bin; Chong, Pele

    2018-05-24

    Hand, foot and mouth diseases (HFMD) are mainly caused by Enterovirus A71 (EV-A71) infections. Clinical trials in Asia conducted with formalin-inactivated EV-A71 vaccine candidates produced from serum-free Vero cell culture using either roller bottle or cell factory technology, are found to be safe and highly efficacious. To increase vaccine yields and reduce the production costs, the bioprocess improvement for EV-A71 vaccine manufacturing is currently being investigated. The parameters that could affect and enhance the production yields of EV-A71 virus growth in the microcarrier bioreactor were investigated. The medium replacement culture strategy included a multi-harvested semi-batch process and perfusion technology and was found to increase the production yields more than 7-14 folds. Based on the western blot and cryo-EM analyses of the EV-A71 virus particles produced from either the multi-harvested semi-batch (MHSBC) or perfusion cultures were found to be similar to those virus particles obtained from the single batch culture. Mouse immunogenicity studies indicate that the EV-A71 vaccine candidates produced from the perfusion culture have similar potency to those obtained from single batch bioprocess. The physical structures of the EV-A71 particles revealed by the cryo-EM analysis were found to be spherical capsid particles. These results provide feasible technical bioprocesses for increasing virus yields and the scale up of EV-A71 vaccine manufacturing using the bioreactor cell culture methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Retention of Mercurial Preservatives in Desiccated Biological Products

    PubMed Central

    Pemberton, John R.

    1975-01-01

    A variety of bacterins, vaccines, and antisera retained greater than 90% of their original level of mercurial preservative after lyophilization, and this might influence certain uses of these products. PMID:1420

  2. Systems biology as a conceptual framework for research in family medicine; use in predicting response to influenza vaccination.

    PubMed

    Majnarić-Trtica, Ljiljana; Vitale, Branko

    2011-10-01

    To introduce systems biology as a conceptual framework for research in family medicine, based on empirical data from a case study on the prediction of influenza vaccination outcomes. This concept is primarily oriented towards planning preventive interventions and includes systematic data recording, a multi-step research protocol and predictive modelling. Factors known to affect responses to influenza vaccination include older age, past exposure to influenza viruses, and chronic diseases; however, constructing useful prediction models remains a challenge, because of the need to identify health parameters that are appropriate for general use in modelling patients' responses. The sample consisted of 93 patients aged 50-89 years (median 69), with multiple medical conditions, who were vaccinated against influenza. Literature searches identified potentially predictive health-related parameters, including age, gender, diagnoses of the main chronic ageing diseases, anthropometric measures, and haematological and biochemical tests. By applying data mining algorithms, patterns were identified in the data set. Candidate health parameters, selected in this way, were then combined with information on past influenza virus exposure to build the prediction model using logistic regression. A highly significant prediction model was obtained, indicating that by using a systems biology approach it is possible to answer unresolved complex medical uncertainties. Adopting this systems biology approach can be expected to be useful in identifying the most appropriate target groups for other preventive programmes.

  3. Influenza Vaccines: Challenges and Solutions

    PubMed Central

    Houser, Katherine; Subbarao, Kanta

    2015-01-01

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

  4. Constructing target product profiles (TPPs) to help vaccines overcome post-approval obstacles

    PubMed Central

    Lee, Bruce Y.; Burke, Donald S.

    2012-01-01

    As history has demonstrated, post-approval obstacles can impede a vaccine’s use and potentially lead to its withdrawal. Addressing these potential obstacles when changes in a vaccine’s technology can still be easily made may improve a vaccine’s chances of success. Augmented vaccine target product profiles (TPPs) can help vaccine scientists better understand and anticipate these obstacles and galvanize conversations among various vaccine stakeholders (e.g., scientists, marketers, business development managers, policy makers, public health officials, health care workers, third party payors, etc.) earlier in a vaccine’s development. PMID:19782109

  5. Construction of live vaccines by using genetically engineered poxviruses: biological activity of recombinant vaccinia virus expressing influenza virus hemagglutinin.

    PubMed Central

    Panicali, D; Davis, S W; Weinberg, R L; Paoletti, E

    1983-01-01

    Recombinant vaccinia viruses containing the cloned hemagglutinin (HA) gene from influenza virus were constructed. The biological activity of these poxvirus vectors was demonstrated both in vitro and in vivo. Expression of HA in cells infected with recombinant vaccinia was detected by using specific anti-HA antiserum and 125I-labeled protein A, showing that HA synthesized under the regulation of vaccinia virus was antigenic. Immunization of rabbits with these recombinant poxviruses resulted in the production of antibodies reactive with authentic influenza HA as detected by radioimmunoassay, by inhibition of HA erythrocyte agglutination, and by neutralization of influenza virus infectivity. The production of antibodies directed against influenza HA suggested that the HA gene expressed in vaccinia is immunogenic. These data indicate the potential of genetically engineered poxviruses for use as generic live vaccine vehicles that have both human and veterinary applications. Images PMID:6310573

  6. Persistence of T-cell immune response induced by two acellular pertussis vaccines in children five years after primary vaccination.

    PubMed

    Palazzo, Raffaella; Carollo, Maria; Bianco, Manuela; Fedele, Giorgio; Schiavoni, Ilaria; Pandolfi, Elisabetta; Villani, Alberto; Tozzi, Alberto E; Mascart, Françoise; Ausiello, Clara M

    2016-01-01

    The resurgence of pertussis suggests the need for greater efforts to understand the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of T memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac® vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa® (Infanrix) (Glaxo-SmithKline Biologicals). We evaluated magnitude and duration of T-cell responses to pertussis toxin (PT) by measuring T-cell proliferation, cytokines (IL-2 and IFNγ) production and memory subsets in two groups of children 5 years after primary vaccination. Some of the enrolled children received only primary vaccination, while others had the pre-school boost dose. Positive T-cell responses to PT were detected in 36% of children. Percentage of responsive children, T-cell proliferation and CD4IL-2+ cells were significantly higher in the children primed with Hexavac than in those who received Infanrix vaccine. No major effects of the boost on PT-specific proliferation were observed. Overall, our data documented a persistence of T-cell memory against PT in a minor fraction of children 5 years after primary vaccination. The different responses induced by Hexavac and Infanrix vaccine could rely on differences in PT inactivation process or excipients/adjuvants formulations.

  7. Synthetic biology: Emerging bioengineering in Indonesia

    NASA Astrophysics Data System (ADS)

    Suhandono, Sony

    2017-05-01

    The development of synthetic biology will shape the new era of science and technology. It is an emerging bioengineering technique involving genetic engineering which can alter the phenotype and behavior of the cell or the new product. Synthetic biology may produce biomaterials, drugs, vaccines, biosensors, and even a recombinant secondary metabolite used in herbal and complementary medicine, such as artemisinin, a malaria drug which is usually extracted from the plant Artemisia annua. The power of synthetic biology has encouraged scientists in Indonesia, and is still in early development. This paper also covers some research from an Indonesian research institute in synthetic biology such as observing the production of bio surfactants and the enhanced production of artemisinin using a transient expression system. Synthetic biology development in Indonesia may also be related to the iGEM competition, a large synthetic biology research competition which was attended by several universities in Indonesia. The application of synthetic biology for drug discovery will be discussed.

  8. Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants.

    PubMed

    Kashima, Koji; Yuki, Yoshikazu; Mejima, Mio; Kurokawa, Shiho; Suzuki, Yuji; Minakawa, Satomi; Takeyama, Natsumi; Fukuyama, Yoshiko; Azegami, Tatsuhiko; Tanimoto, Takeshi; Kuroda, Masaharu; Tamura, Minoru; Gomi, Yasuyuki; Kiyono, Hiroshi

    2016-03-01

    The first Good Manufacturing Practices production of a purification-free rice-based oral cholera vaccine (MucoRice-CTB) from transgenic plants in a closed cultivation system yielded a product meeting regulatory requirements. Despite our knowledge of their advantages, plant-based vaccines remain unavailable for human use in both developing and industrialized countries. A leading, practical obstacle to their widespread use is producing plant-based vaccines that meet governmental regulatory requirements. Here, we report the first production according to current Good Manufacturing Practices of a rice-based vaccine, the cholera vaccine MucoRice-CTB, at an academic institution. To this end, we established specifications and methods for the master seed bank (MSB) of MucoRice-CTB, which was previously generated as a selection-marker-free line, evaluated its propagation, and given that the stored seeds must be renewed periodically. The production of MucoRice-CTB incorporated a closed hydroponic system for cultivating the transgenic plants, to minimize variations in expression and quality during vaccine manufacture. This type of molecular farming factory can be operated year-round, generating three harvests annually, and is cost- and production-effective. Rice was polished to a ratio of 95 % and then powdered to produce the MucoRice-CTB drug substance, and the identity, potency, and safety of the MucoRice-CTB product met pre-established release requirements. The formulation of MucoRice-CTB made by fine-powdering of drug substance and packaged in an aluminum pouch is being evaluated in a physician-initiated phase I study.

  9. Cancer vaccine characterization: from bench to clinic.

    PubMed

    de la Luz-Hernández, K; Rabasa, Y; Montesinos, R; Fuentes, D; Santo-Tomás, J F; Morales, O; Aguilar, Y; Pacheco, B; Castillo, A

    2014-05-19

    The development of safe, effective, and affordable vaccines has become a global effort due to its vast impact on overall world health conditions. A brief overview of vaccine characterization techniques, especially in the area of high-resolution mass spectrometry, is presented. It is highly conceivable that the proper use of advanced technologies such as high-resolution mass spectrometry, along with the appropriate chemical and physical property evaluations, will yield tremendous in-depth scientific understanding for the characterization of vaccines in various stages of vaccine development. This work presents the physicochemical and biological characterization of cancer vaccine Racotumomab/alumina, a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. Racotumomab was obtained from ascites fluid, transferred to fermentation in stirred tank at 10 L and followed to a scale up to 41 L. The mass spectrometry was used for the determination of intact molecule, light and heavy chains masses; amino acids sequence analysis, N- and C-terminal, glycosylation and posttranslational modifications. Also we used the DLS for the size distribution and zeta potential analysis. The biological analyses were performed in mice and chickens. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced and bioreactor-obtained Racotumomab products. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. We are demonstrated that this approach could potentially be more efficient and effective for supporting vaccine research and development. Copyright © 2014. Published by Elsevier Ltd.

  10. 75 FR 55776 - Request for Comments on Vaccine Production and Additional Planning for Future Possible Pandemic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... DEPARTMENT OF COMMERCE International Trade Administration Request for Comments on Vaccine... Administration invites submission of comments from the public and relevant industries on vaccine production and...: E-mail: Vaccine[email protected] . Fax: (202) 482-1975 (Attn.: Jane Earley). Mail or Hand Delivery...

  11. An Automated HIV-1 Env-Pseudotyped Virus Production for Global HIV Vaccine Trials

    PubMed Central

    Fuss, Martina; Mazzotta, Angela S.; Sarzotti-Kelsoe, Marcella; Ozaki, Daniel A.; Montefiori, David C.; von Briesen, Hagen; Zimmermann, Heiko; Meyerhans, Andreas

    2012-01-01

    Background Infections with HIV still represent a major human health problem worldwide and a vaccine is the only long-term option to fight efficiently against this virus. Standardized assessments of HIV-specific immune responses in vaccine trials are essential for prioritizing vaccine candidates in preclinical and clinical stages of development. With respect to neutralizing antibodies, assays with HIV-1 Env-pseudotyped viruses are a high priority. To cover the increasing demands of HIV pseudoviruses, a complete cell culture and transfection automation system has been developed. Methodology/Principal Findings The automation system for HIV pseudovirus production comprises a modified Tecan-based Cellerity system. It covers an area of 5×3 meters and includes a robot platform, a cell counting machine, a CO2 incubator for cell cultivation and a media refrigerator. The processes for cell handling, transfection and pseudovirus production have been implemented according to manual standard operating procedures and are controlled and scheduled autonomously by the system. The system is housed in a biosafety level II cabinet that guarantees protection of personnel, environment and the product. HIV pseudovirus stocks in a scale from 140 ml to 1000 ml have been produced on the automated system. Parallel manual production of HIV pseudoviruses and comparisons (bridging assays) confirmed that the automated produced pseudoviruses were of equivalent quality as those produced manually. In addition, the automated method was fully validated according to Good Clinical Laboratory Practice (GCLP) guidelines, including the validation parameters accuracy, precision, robustness and specificity. Conclusions An automated HIV pseudovirus production system has been successfully established. It allows the high quality production of HIV pseudoviruses under GCLP conditions. In its present form, the installed module enables the production of 1000 ml of virus-containing cell culture supernatant per

  12. Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules

    PubMed Central

    Legastelois, Isabelle; Buffin, Sophie; Peubez, Isabelle; Mignon, Charlotte; Sodoyer, Régis; Werle, Bettina

    2017-01-01

    ABSTRACT The increasing demand for recombinant vaccine antigens or immunotherapeutic molecules calls into question the universality of current protein expression systems. Vaccine production can require relatively low amounts of expressed materials, but represents an extremely diverse category consisting of different target antigens with marked structural differences. In contrast, monoclonal antibodies, by definition share key molecular characteristics and require a production system capable of very large outputs, which drives the quest for highly efficient and cost-effective systems. In discussing expression systems, the primary assumption is that a universal production platform for vaccines and immunotherapeutics will unlikely exist. This review provides an overview of the evolution of traditional expression systems, including mammalian cells, yeast and E.coli, but also alternative systems such as other bacteria than E. coli, transgenic animals, insect cells, plants and microalgae, Tetrahymena thermophila, Leishmania tarentolae, filamentous fungi, cell free systems, and the incorporation of non-natural amino acids. PMID:27905833

  13. Implementation workshop of WHO guidelines on evaluation of malaria vaccines: Current regulatory concepts and issues related to vaccine quality, Pretoria, South Africa 07 Nov 2014.

    PubMed

    Ho, Mei Mei; Baca-Estrada, Maria; Conrad, Christoph; Karikari-Boateng, Eric; Kang, Hye-Na

    2015-08-26

    The current World Health Organization (WHO) guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum were adopted by the WHO Expert Committee on Biological Standardization in 2012 to provide guidance on the quality, nonclinical and clinical aspects of recombinant malaria vaccines. A WHO workshop was organised to facilitate implementation into African (national/regional) regulatory practices, of the regulatory evaluation principles outlined in the guidelines regarding quality aspects. The workshop was used also to share knowledge and experience on regulatory topics of chemistry, manufacturing and control with a focus on vaccines through presentations and an interactive discussion using a case study approach. The basic principles and concepts of vaccine quality including consistency of production, quality control and manufacturing process were presented and discussed in the meeting. By reviewing and practicing a case study, better understanding on the relationship between consistency of production and batch release tests of an adjuvanted pre-erythrocytic recombinant malaria vaccine was reached. The case study exercise was considered very useful to understand regulatory evaluation principles of vaccines and a suggestion was made to WHO to provide such practices also through its Global Learning Opportunities for Vaccine Quality programme. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. European Pharmacopoeia biological reference preparation for poliomyelitis vaccine (inactivated): collaborative study for the establishment of batch No. 3.

    PubMed

    Martin, J; Daas, A; Milne, C

    2016-01-01

    Inactivated poliomyelitis vaccines are an important part of the World Health Organization (WHO) control strategy to eradicate poliomyelitis. Requirements for the quality control of poliomyelitis vaccines (inactivated) include the use of an in vitro D antigen quantification assay for potency determination on the final lot as outlined in the European Pharmacopoeia (Ph. Eur.) monograph 0214. Performance of this assay requires a reference preparation calibrated in International Units (IU). A Ph. Eur. biological reference preparation (BRP) for poliomyelitis vaccine (inactivated) calibrated in IU has been established for this purpose. Due to the dwindling stocks of batch 2 of the BRP a collaborative study was run as part of the European Directorate for the Quality of Medicines & HealthCare (EDQM) Biological Standardisation Programme to establish BRP batch 3 (BRP3). Twelve laboratories including Official Medicines Control Laboratories (OMCLs) and manufacturers participated. The candidate BRP3 (cBRP3) was from the same source and had the same characteristics as BRP batch 2 (BRP2). During the study the candidate was calibrated against the 3 rd International Standard for inactivated poliomyelitis vaccine using in-house D antigen ELISA assays in line with the Ph. Eur. monograph 0214. The candidate was also compared to BRP2 to evaluate the continuity. Based on the results of the study, values of 320 DU/mL, 78 DU/mL and 288 DU/mL (D antigen units/mL) (IU) for poliovirus type 1, 2 and 3 respectively were assigned to the candidate. In June 2016, the Ph. Eur. Commission adopted the material as Ph. Eur. BRP for poliomyelitis vaccine (inactivated) batch 3.

  15. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

    PubMed

    Chou, Ai-Hsiang; Liu, Chia-Chyi; Chang, Cheng-Peng; Guo, Meng-Shin; Hsieh, Shih-Yang; Yang, Wen-Hsueh; Chao, Hsin-Ju; Wu, Chien-Long; Huang, Ju-Lan; Lee, Min-Shi; Hu, Alan Yung-Chi; Lin, Sue-Chen; Huang, Yu-Yun; Hu, Mei-Hua; Chow, Yen-Hung; Chiang, Jen-Ron; Chang, Jui-Yuan; Chong, Pele

    2012-01-01

    Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. These

  16. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Ingredients of biological products... REQUIREMENTS Ingredient Requirements § 113.50 Ingredients of biological products. All ingredients used in a licensed biological product shall meet accepted standards of purity and quality; shall be sufficiently...

  17. Screening vaccine formulations for biological activity using fresh human whole blood

    PubMed Central

    Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression. PMID:24401565

  18. Screening vaccine formulations for biological activity using fresh human whole blood.

    PubMed

    Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.

  19. Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy

    PubMed Central

    Fox, Christopher B.; Barnes V, Lucien; Evers, Tara; Chesko, James D.; Vedvick, Thomas S.; Coler, Rhea N.; Reed, Steven G.; Baldwin, Susan L.

    2012-01-01

    Please cite this paper as: Fox et al. (2012) Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12031. Abstract Background  Adjuvant formulations are critical components of modern vaccines based on recombinant proteins, which are often poorly immunogenic without additional immune stimulants. Oil‐in‐water emulsions comprise an advanced class of vaccine adjuvants that are components of approved seasonal and pandemic influenza vaccines. However, few reports have been published that systematically evaluate the in vitro stability and in vivo adjuvant effects of different emulsion components. Objectives  To evaluate distinct classes of surfactants, oils, and excipients, for their effects on emulsion particle size stability, antigen structural interactions, and in vivo activity when formulated with a recombinant H5N1 antigen. Methods  Emulsions were manufactured by high pressure homogenization and characterized alone or in the presence of vaccine antigen by dynamic light scattering, zeta potential, viscosity, pH, hemolytic activity, electron microscopy, fluorescence spectroscopy, and SDS‐PAGE. In vivo vaccine activity in the murine model was characterized by measuring antibody titers, antibody‐secreting plasma cells, hemagglutination inhibition titers, and cytokine production. Results  We demonstrate that surfactant class and presence of additional excipients are not critical for biological activity, whereas oil structure is crucial. Moreover, we report that simplified two‐component emulsions appear more stable by particle size than more complex formulations.Finally, differences in antigen structural interactions with the various emulsions do not appear to correlate with in vivo activity. Conclusions  Oil‐in‐water emulsions can significantly enhance antibody and cellular immune responses to a pandemic influenza

  20. Financial impact to providers using pediatric combination vaccines.

    PubMed

    Shen, Angela K; Sobczyk, Elizabeth; Simonsen, Lone; Khan, Farid; Esber, Allahna; Andreae, Margie C

    2011-12-01

    To understand the financial impact to providers for using a combination vaccine (Pediarix [GlaxoSmithKline Biologicals, King of Prussia, PA]) versus its equivalent component vaccines for children aged 1 year or younger. Using a subscription remittance billing service offered to private-practice office-based physicians, we analyzed charge and payment information submitted by providers to insurance payers from June 2007 through July 2009. We analyzed provider and payer characteristics, payer comments, and the ratio of vaccine product to immunization administration (IA) codes and computed total charges and payments to providers for both arms of the study. Most providers in our data set were pediatricians (74%), and most payers were commercial (75%), primarily managed care. The ratio of the number of vaccine products to the number of IAs was 1:1 in the majority of the claims. Twenty percent of claims were paid with no adjustment by the payer, whereas 76% of the claims were adjusted for charges that exceeded the contract arrangement or the fee schedule. Providers received $23 less from commercial payers and $13 less from Medicaid for the use of Pediarix compared with the equivalent component vaccines. The mean commercial payment was greater for age-specific Current Procedural Terminology IA codes 90465 and 90466 than for non-age-specific codes 90471 and 90472, whereas the reverse was true for Medicaid. Providers who administer vaccines to children face a reduction in payment when choosing to provide combination vaccines. The new IA codes should be monitored for correction of financial barriers to the use of combination vaccines.

  1. 9 CFR 113.313 - Measles Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

  2. 9 CFR 113.313 - Measles Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

  3. 9 CFR 113.313 - Measles Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

  4. 9 CFR 113.313 - Measles Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

  5. 9 CFR 113.313 - Measles Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

  6. Physicochemical and biological characterization of 1E10 Anti-Idiotype vaccine

    PubMed Central

    2011-01-01

    Background 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method. Results Here, we present a comprehensive molecular and immunological characterization of 1E10 produced by the two different production processes in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced 1E10 and bioreactor-obtained 1E10. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. Conclusions Changes in 1E10 primary structure like glycosylation; asparagine deamidation and oxidation affected 1E10 structural stability but did not affect the immune response elicited in mice and chickens when compared to 1E10 produced in mice. PMID:22108317

  7. MMR Vaccine (Measles, Mumps, and Rubella)

    MedlinePlus

    Attenuvax® Measles Vaccine ... R-Vax® II (as a combination product containing Measles Vaccine, Rubella Vaccine) ... M-R® II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  8. Development of a vaccine to mitigate greenhouse gas emissions in agriculture: vaccination of sheep with methanogen fractions induces antibodies that block methane production in vitro.

    PubMed

    Wedlock, D N; Pedersen, G; Denis, M; Dey, D; Janssen, P H; Buddle, B M

    2010-02-01

    To develop an understanding of the immune responses of ruminants to methanogens, and to provide proof of a concept that harnessing the immune system of ruminants is a potentially viable approach to mitigate greenhouse gas emissions from agriculture. Four subcellular fractions, namely cytoplasmic, two cell-wall preparations, and cell wall-derived proteins were prepared from Methanobrevibacter ruminantium M1. Twenty sheep (10 months of age) were vaccinated with these fractions or with whole cells (n=4 per group). Sheep were re-vaccinated once after 3 weeks, and antibody responses to M. ruminantium M1 antigens in sera and saliva measured using ELISA at 2 weeks after the second vaccination. Antigens recognised by the antisera were visualised using Western blotting. The antisera were tested in vitro for their impact on M. ruminantium M1, measuring the effect on cell growth, methane production, and ability to induce agglutination. Basal levels (pre-vaccination) of antibodies against M. ruminantium M1 antigens were low. Vaccination with the antigenic fractions induced strong antibody responses in serum. Both IgG and IgA responses to methanogen antigens were detected in saliva following vaccination. Western blot analysis of the antisera indicated reactivity of antibodies, and a wide range of proteins was present in the different methanogen fractions. Antisera against the various fractions agglutinated methanogens in an in-vitro assay. In addition, these antisera decreased the growth of a pure culture of a methanogen and production of methane in vitro. Antigens from methanogens are immunogenic in ruminants, and antisera from sheep vaccinated with fractions of methanogens have a significant impact on these organisms, inducing cell agglutination, and decreasing growth of methanogens and production of methane. Only antisera to selected methanogen fractions were able to achieve these effects. The results demonstrate the feasibility of a vaccination strategy to mitigate emission

  9. First evaluation of endotoxins in veterinary autogenous vaccines produced in Italy by LAL assay.

    PubMed

    Antonella, Di Paolo; Katia, Forti; Lucia, Anzalone; Sara, Corneli; Martina, Pellegrini; Giulio, Severi; Monica, Cagiola

    2018-06-21

    Endotoxin contamination is a serious concern for manufacturers of biological products and vaccines in terms of not only quality but also safety parameters. We evaluated the endotoxin presence in different veterinary autogenous vaccines produced by the Pharmaceutical Unit at the Experimental Zooprophylactic Institute of Umbria and Marche "Togo Rosati" (IZSUM). According to the 3Rs principles (Replace, Reduce, Refine), which aim to progressively reduce animal use in the quality control process, we tested the vaccines obtained from gram-negative bacteria and adjuvants by the limulus amebocyte lysate (LAL) assay. The results revealed low endotoxin concentrations compared to available data in the literature and represent the first report of the application of the 3Rs principles to veterinary autogenous vaccines production in Italy. Copyright © 2018. Published by Elsevier Ltd.

  10. Robust real-time cell analysis method for determining viral infectious titers during development of a viral vaccine production process.

    PubMed

    Charretier, Cédric; Saulnier, Aure; Benair, Loïc; Armanet, Corinne; Bassard, Isabelle; Daulon, Sandra; Bernigaud, Bertrand; Rodrigues de Sousa, Emanuel; Gonthier, Clémence; Zorn, Edouard; Vetter, Emmanuelle; Saintpierre, Claire; Riou, Patrice; Gaillac, David

    2018-02-01

    The classical cell-culture methods, such as cell culture infectious dose 50% (CCID 50 ) assays, are time-consuming, end-point assays currently used during the development of a viral vaccine production process to measure viral infectious titers. However, they are not suitable for handling the large number of tests required for high-throughput and large-scale screening analyses. Impedance-based bio-sensing techniques used in real-time cell analysis (RTCA) to assess cell layer biological status in vitro, provide real-time data. In this proof-of-concept study, we assessed the correlation between the results from CCID 50 and RTCA assays and compared time and costs using monovalent and tetravalent chimeric yellow fever dengue (CYD) vaccine strains. For the RTCA assay, Vero cells were infected with the CYD sample and real-time impedance was recorded, using the dimensionless cell index (CI). The CI peaked just after infection and decreased as the viral cytopathic effect occurred in a dose-dependent manner. The time to the median CI (CIT med ) was correlated with viral titers determined by CCID 50 over a range of about 4-5log 10 CCID 50 /ml. This in-house RTCA virus-titration assay was shown to be a robust method for determining real-time viral infectious titers, and could be an alternative to the classical CCID 50 assay during the development of viral vaccine production process. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Potency assays for therapeutic live whole cell cancer vaccines.

    PubMed

    Petricciani, John; Egan, William; Vicari, Giuseppe; Furesz, John; Schild, Geoffrey

    2007-04-01

    Therapeutic cancer vaccines are under development with the goal of enhancing the body's immune response to cancer cells sufficient to arrest cancer cell growth. Among the various approaches being used are those based on whole tumor cells. Developing a suitable measure of the potency of such vaccines presents a significant challenge because neither cellular associated markers nor in vivo biological responses that are correlated with efficacy have been identified; nevertheless, manufacturers and regulatory agencies will need to develop methods to evaluate these products. At this moment, the challenge for manufacturers who are developing whole cell vaccines is to demonstrate batch-to-batch consistency for the vaccine used in clinical studies and to show that comparable vaccine batches have the same capacity to achieve an acceptable level of biological activity that may be related to efficacy. This is particularly challenging in that animal models to test that activity do not exist and direct serological or immunological correlates of clinical protection are not available because protection has not yet been established in clinical trials. In the absence of well-defined biological markers and tests for manufacturing consistency, manufacturers and regulators will need to rely heavily on a highly reproducible manufacturing process--the consistency of the process therefore becomes critical. In developing regulatory approaches to whole cell cancer vaccines, the experience from the field of infectious disease vaccines should be examined for general guidance. A framework that draws heavily on the field of infectious disease vaccines is presented and suggests that at this point in the development of this new class of products, it is reasonable to develop data on quantitative antigen expression as a measure of potency with the expectation that when clinical efficacy has been established it will confirm the appropriateness of this approach. But because this will not be known

  12. ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense.

    PubMed

    Monath, Thomas P; Caldwell, Joseph R; Mundt, Wolfgang; Fusco, Joan; Johnson, Casey S; Buller, Mark; Liu, Jian; Gardner, Bridget; Downing, Greg; Blum, Paul S; Kemp, Tracy; Nichols, Richard; Weltzin, Richard

    2004-10-01

    The threat of smallpox as a biological weapon has spurred efforts to create stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in animal skin (the original method), we cloned vaccinia virus (New York City Board of Health strain, Dryvax by plaque purification and amplified the clone in cell culture. The overarching goal was to produce a modern vaccine that was equivalent to the currently licensed Dryvax in its preclinical and clinical properties, and could thus reliably protect humans against smallpox. A variety of clones were evaluated, and many were unacceptably virulent in animal models. One clonal virus (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid cells. ACAM1000 was comparable to Dryvax in immunogenicity and protective activity but was less neurovirulent for mice and nonhuman primates. To meet requirements for large quantities of vaccine after the events of September 11th 2001, the ACAM1000 master virus seed was used to prepare vaccine (designated ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three Phase 1 clinical trials. The vaccines produced major cutaneous reactions and evoked neutralizing antibody and cell-mediated immune responses in the vast majority of subjects and had a reactogenicity profile similar to that of Dryvax.

  13. US FDA review and regulation of preventive vaccines for infectious disease indications: impact of the FDA Amendments Act 2007.

    PubMed

    Gruber, Marion F

    2011-07-01

    Vaccines for prevention or treatment of infectious diseases are biological products that are regulated by the Office of Vaccines Research and Review in the Center for Biologics Evaluation and Research of the US FDA. The legal framework for the regulation of vaccines derives primarily from Section 351 of the Public Health Service Act and from certain sections of the Federal Food, Drug and Cosmetic Act (FFD & C Act). The FDA Amendments Act of 2007 (FDAAA 2007) includes extensive modifications to the FFD & C Act. This article provides an overview of the review process for preventive vaccines and highlights applicable statutory provisions. In addition, this article will discuss changes in the pre-and post-licensure evaluation process for preventive and therapeutic infectious disease vaccines since implementation of the FDAAA 2007.

  14. 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.

  15. Reviewing the importance of the cold chain in the distribution of vaccines.

    PubMed

    Purssell, Edward

    2015-10-01

    Vaccination is an effective public health measure to prevent and control a number of infectious diseases. However, since vaccines are biological products and are sensitive to both heat and cold, they need to be maintained within a narrow range of temperatures, often referred to as the 'cold-chain'. This range, which is between +2°C and +8°C with a target +5°C, does not allow for refreezing or storage at room temperature. This paper discusses the importance of the cold chain, what should be done both to maintain it, and the actions to be taken, should a break be noted. It is important to note the product information supplied with vaccines, which is taken from the summary of product characteristics that forms part of the licensing requirements for each vaccine, and which will state how it should be stored. Using a vaccine that has not been stored according to these instructions constitutes off-label use, for which the individual practitioner must take responsibility. It also emphasises the fragile nature of many public health interventions, maintenance of which require constant vigilance and close cooperation between many groups and individuals.

  16. Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial.

    PubMed

    Smith, Larry R; Wloch, Mary K; Chaplin, Jennifer A; Gerber, Michele; Rolland, Alain P

    2013-09-25

    2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine's planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV⁺) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV⁺ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.

  17. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Preparation of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of experimental biological products. Except as otherwise provided in this section, experimental biological...

  18. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Preparation of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of experimental biological products. Except as otherwise provided in this section, experimental biological...

  19. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Preparation of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of experimental biological products. Except as otherwise provided in this section, experimental biological...

  20. Research toward Malaria Vaccines

    NASA Astrophysics Data System (ADS)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  1. 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

  2. Hepatitis B Vaccine

    MedlinePlus

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  3. Recombinant LipL32 stimulates interferon-gamma production in cattle vaccinated with a monovalent Leptospira borgpetersenii serovar Hardjo subtype Hardjobovis vaccine.

    PubMed

    Deveson Lucas, Deanna S; Lo, Miranda; Bulach, Dieter M; Quinsey, Noelene S; Murray, Gerald L; Allen, Andy; Adler, Ben

    2014-03-14

    Leptospira borgpetersenii serovar Hardjo subtype Hardjobovis (Hardjobovis) is the main causative agent of bovine leptospirosis in Australia, New Zealand, North America and elsewhere. Bovine leptospirosis can result in spontaneous abortion, stillbirth and reduced milk output. The organism is shed in the urine of infected animals and contact with contaminated materials can result in zoonotic infections in humans. Protective immunity in cattle against Hardjobovis involves stimulation of a Th1 cell mediated immune response, which can be characterized by the production of IFN-γ when blood from vaccinated animals is exposed to Hardjobovis antigens. However, the leptospiral components involved in stimulating this response have yet to be identified. In this study, 238 recombinant leptospiral proteins were evaluated for their ability to stimulate IFN-γ production in blood of cattle vaccinated with a commercial monovalent Hardjobovis vaccine. The conserved lipoprotein LipL32 is the major outer membrane protein of pathogenic Leptospira spp. A pool of soluble recombinant proteins which included LipL32, as well as LipL32 alone, stimulated significant IFN-γ production in blood of vaccinated cattle. A number of recombinant LipL32 fragments was generated, which identified the amino acids between 20 and 200 as containing the bovine T-cell reactive regions of LipL32. However, whether LipL32 plays a role in stimulating protective immunity in mammals has yet to be conclusively determined. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Varicella (Chickenpox) Vaccine

    MedlinePlus

    ProQuad® (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine, Varicella Vaccine) ... Has a parent, brother, or sister with a history of immune system problems. Is taking salicylates (such ...

  5. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false U.S. Veterinary Biological Product... BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a) Authorization to produce each biological product shall be specified on a U.S. Veterinary Biological Product License, issued by the...

  6. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false U.S. Veterinary Biological Product... BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a) Authorization to produce each biological product shall be specified on a U.S. Veterinary Biological Product License, issued by the...

  7. [History of vaccination: from empiricism towards recombinant vaccines].

    PubMed

    Guérin, N

    2007-01-01

    Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.

  8. Vaccine supply, demand, and policy: a primer.

    PubMed

    Muzumdar, Jagannath M; Cline, Richard R

    2009-01-01

    To provide an overview of supply and demand issues in the vaccine industry and the policy options that have been implemented to resolve these issues. Medline, Policy File, and International Pharmaceutical Abstracts were searched to locate academic journal articles. Other sources reviewed included texts on the topics of vaccine history and policy, government agency reports, and reports from independent think tanks. Keywords included vaccines, immunizations, supply, demand, and policy. Search criteria were limited to English language and human studies. Articles pertaining to vaccine demand, supply, and public policy were selected and reviewed for inclusion. By the authors. Vaccines are biologic medications, therefore making their development and production more difficult and costly compared with "small-molecule" drugs. Research and development costs for vaccines can exceed $800 million, and development may require 10 years or more. Strict manufacturing regulations and facility upgrades add to these costs. Policy options to increase and stabilize the supply of vaccines include those aimed at increasing supply, such as government subsidies for basic vaccine research, liability protection for manufacturers, and fast-track approval for new vaccines. Options to increase vaccine demand include advance purchase commitments, government stockpiles, and government financing for select populations. High development costs and multiple barriers to entry have led to a decline in the number of vaccine manufacturers. Although a number of vaccine policies have met with mixed success in increasing the supply of and demand for vaccines, a variety of concerns remain, including developing vaccines for complex pathogens and increasing immunization rates with available vaccines. New policy innovations such as advance market commitments and Medicare Part D vaccine coverage have been implemented and may aid in resolving some of the problems in the vaccine industry.

  9. Novel immunotherapy vaccine development.

    PubMed

    Jutel, Marek; Akdis, Cezmi A

    2014-12-01

    Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies. The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

  10. Impact of BRICS’ investment in vaccine development on the global vaccine market

    PubMed Central

    Milstien, Julie; Schmitt, Sarah

    2014-01-01

    Abstract 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

  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.

  12. Variability in biological behaviour, pathogenicity, protectotype and induction of virus neutralizing antibodies by different vaccination programmes to infectious bronchitis virus genotype Q1 strains from Chile.

    PubMed

    de Wit, J J; Dijkman, R; Guerrero, P; Calvo, J; Gonzalez, A; Hidalgo, H

    2017-12-01

    In the period from July 2008 to 2010, a disease episode resulting in serious economic losses in the major production area of the Chilean poultry industry was reported. These losses were associated with respiratory problems, increase of condemnations, drops in egg production and nephritis in breeders, laying hens and broilers due to infections with infectious bronchitis virus (IBV). Twenty-five IBV isolates were genotyped and four strains were selected for further testing by pathotyping and protectotyping. Twenty-four IBV isolates were of the Q1 genotype. The experiments also included comparing the ability of six vaccination programmes to induce virus neutralizing antibodies (VNA) in layers against four selected Chilean strains. Despite the high genetic homology in the S1 gene between the four strains, the heterogeneity in biological behaviour of these different Q1 strains was substantial. These differences were seen in embryonated eggs, in cell culture, in pathogenicity and in level of cross-protection by IBV Massachusetts (Mass) vaccination. This variability underlines the importance of testing more than one strain per serotype or genotype to determine the characteristics of a certain serotype of genotype. The combination of Mass and 793B vaccine provided a high level of protection to the respiratory tract and the kidney for each strain tested in the young birds. The combination of broad live priming using Mass and 793B vaccines and boosting with multiple inactivated IBV antigens induced the highest level of VNA against Q1 strains, which might be indicative for higher levels of protection against Q1 challenge in laying birds.

  13. Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes

    PubMed Central

    Kon, Theone C.; Onu, Adrian; Berbecila, Laurentiu; Lupulescu, Emilia; Ghiorgisor, Alina; Kersten, Gideon F.; Cui, Yi-Qing; Amorij, Jean-Pierre; Van der Pol, Leo

    2016-01-01

    The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween®, either Triton™ X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months. PMID:26959983

  14. Development of vaccines for bio-warfare agents.

    PubMed

    Rosenthal, S R; Clifford, J C M

    2002-01-01

    There is a recognized need for the development of new vaccines (as well as other biologicals and drugs) to counteract the effects of a potential bio-terrorist or bio-warfare event in the U.S. domestic population and military forces. Regulation of products to protect against potential bio-warfare agents poses unique challenges since the usual measures of efficacy that require exposure to natural disease may not currently be possible, for epidemiological and ethical reasons. To help to address this issue, the FDA has published and requested comments on a proposed animal rule intended to address certain efficacy issues for new agents for use against lethal or permanently disabling toxic substances. Recent product development activity has focused on Bacillus anthracis (anthrax) and variola major (smallpox), agents that are regarded as highest priority in posing a risk to national security. FDA resources exist to assist vaccine developers with regard to the novel challenges posed in the dinical development of these products.

  15. Design control considerations for biologic-device combination products.

    PubMed

    Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

    2017-03-01

    Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting

  16. Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

    PubMed

    Mahoney, R T; Francis, D P; Frazatti-Gallina, N M; Precioso, A R; Raw, I; Watler, P; Whitehead, P; Whitehead, S S

    2012-07-06

    A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. Although this study does not seek to compute the price of the final

  17. Biosynthesis of therapeutic natural products using synthetic biology.

    PubMed

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients.

    PubMed

    Cooper, Cristine J; Metch, Barbara; Dragavon, Joan; Coombs, Robert W; Baden, Lindsey R

    2010-07-21

    Induction of protective anti-human immunodeficiency virus (HIV) immune responses is the goal of an HIV vaccine. However, this may cause a reactive result in routine HIV testing in the absence of HIV infection. To evaluate the frequency of vaccine-induced seropositivity/reactivity (VISP) in HIV vaccine trial participants. Three common US Food and Drug Administration-approved enzyme immunoassay (EIA) HIV antibody kits were used to determine VISP, and a routine diagnostic HIV algorithm was used to evaluate VISP frequency in healthy, HIV-seronegative adults who completed phase 1 (n = 25) and phase 2a (n = 2) vaccine trials conducted from 2000-2010 in the United States, South America, Thailand, and Africa. Vaccine-induced seropositivity/reactivity, defined as reactive on 1 or more EIA tests and either Western blot-negative or Western blot-indeterminate/atypical positive (profile consistent with vaccine product) and HIV-1-negative by nucleic acid testing. Among 2176 participants free of HIV infection who received a vaccine product, 908 (41.7%; 95% confidence interval [CI], 39.6%-43.8%) had VISP, but the occurrence of VISP varied substantially across different HIV vaccine product types: 399 of 460 (86.7%; 95% CI, 83.3%-89.7%) adenovirus 5 product recipients, 295 of 552 (53.4%; 95% CI, 49.2%-57.7%) recipients of poxvirus alone or as a boost, and 35 of 555 (6.3%; 95% CI, 4.4%-8.7%) of DNA-alone product recipients developed VISP. Overall, the highest proportion of VISP (891/2176 tested [40.9%]) occurred with the HIV 1/2 (rDNA) EIA kit compared with the rLAV EIA (150/700 tested [21.4%]), HIV-1 Plus O Microelisa System (193/1309 tested [14.7%]), and HIV 1/2 Peptide and HIV 1/2 Plus O (189/2150 tested [8.8%]) kits. Only 17 of the 908 participants (1.9%) with VISP tested nonreactive using the HIV 1/2 (rDNA) kit. All recipients of a glycoprotein 140 vaccine (n = 70) had VISP, with 94.3% testing reactive with all 3 EIA kits tested. Among 901 participants with VISP and a Western

  19. Optimization of a methamphetamine conjugate vaccine for antibody production in mice.

    PubMed

    Stevens, Misty W; Gunnell, Melinda G; Tawney, Rachel; Owens, S Michael

    2016-06-01

    There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Pharmacy management of vaccines.

    PubMed

    Cannon, H Eric

    2007-09-01

    Although standard vaccines have traditionally been granted full coverage in managed care, the recent introduction of several novel vaccine products has necessitated the revision of pharmacy management strategies throughout the nation. To review pharmacy management strategies for a number of emerging vaccines, with unique plan perspectives from SelectHealth, an Intermountain Healthcare company serving approximately 500,000 members in Utah. Because several recently introduced vaccines target previously unaddressed diseases and carry higher costs than traditional vaccines, several plans have adapted a novel approach to manage vaccine coverage on an individual product basis. At SelectHealth, recently introduced vaccines for rotavirus, respiratory syncytial virus (RSV), herpes zoster, and human papillomavirus (HPV) have required special attention in terms of pharmacy management. After carefully weighing acquisition and administration costs, anticipated uptake and use, direct and indirect health care costs averted, and quality of life issues, plan leadership decided to cover many of the new vaccines (i.e., rotavirus, RSV, and herpes zoster) under a nonstandard vaccination benefit. However, because substantial cost savings and high use of the quadrivalent HPV vaccine was anticipated within SelectHealth, the plan decided to fully cover the product. Although they complicate traditional pharmacy management, novel vaccines provide clinical benefit that managed care organizations cannot ignore. One universal strategy will not suffice in managing all the different vaccines entering the market, and a tailored approach should be employed based on the individual characteristics and use of each product.

  1. The effects of stopper drying on moisture levels of Haemophilus influenzae conjugate vaccine.

    PubMed

    Earle, J P; Bennett, P S; Larson, K A; Shaw, R

    1992-01-01

    The discovery and development of increasingly potent biological and pharmaceutical products have resulted in very small amounts of the active ingredient in final product formulations. Pediatric vaccines with sub-milliliter dose sizes pose unique problems for final formulation and lyophilization, especially when stabilizers used are present in small amounts or are hygroscopic. Lyophilized Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PedvaxHIB) has a plug weight of about 3 mg in its final formulation. Microgram amounts of water absorbed by the lyophilized plug can cause drastic changes in the moisture content of the product. In a small percentage of the final containers absorption of moisture by the vaccine may cause aesthetic defects (plug collapse) over time, or at elevated temperatures. This paper describes drying methods developed to control residual moisture levels in stoppers used as final container closures. Results on the moisture stability of the product capped with dried and non-dried stoppers are presented.

  2. Parasite Carbohydrate Vaccines.

    PubMed

    Jaurigue, Jonnel A; Seeberger, Peter H

    2017-01-01

    Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases-malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma , and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development.

  3. Parasite Carbohydrate Vaccines

    PubMed Central

    Jaurigue, Jonnel A.; Seeberger, Peter H.

    2017-01-01

    Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases—malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma, and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development. PMID:28660174

  4. Plankton Production Biology

    DTIC Science & Technology

    2013-09-30

    population dynamics (growth rate, production, mortality) of copepod nauplii in the field or captured water columns (mesocosms). Since biology...36-45, doi:10.1016/j.dsr.2012.03.001, 2012. PUBLICATIONS Banse, K., Naqvi, S.W.A., Narvekar, P.V., Postel, J.R., Jayakumar , D.A. Oxygen minimum

  5. WHO policy development processes for a new vaccine: case study of malaria vaccines.

    PubMed

    Milstien, Julie; Cárdenas, Vicky; Cheyne, James; Brooks, Alan

    2010-06-24

    Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions. WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues. Although policy issues may be more complex for future vaccines

  6. [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)

  7. Effects of 2 commercially-available 9-way killed vaccines on milk production and rectal temperature in Holstein-Friesian dairy cows.

    PubMed Central

    Scott, H M; Atkins, G; Willows, B; McGregor, R

    2001-01-01

    Veterinarians and farmers employing multivalent killed vaccines in lactating dairy cows have reported transient losses in milk production. Few studies have quantified this loss. In this report, effects of 2 commercially available 9-way vaccines on milk production and rectal temperature are examined. Repeated measures analyses of variance were used to compare changes in milk production and rectal temperature over time between treatment groups. There was a significant (P < 0.01) interaction among treatment and time when comparing vaccine- and placebo-treated animals. When pretreatment milk production (or days in milk) and pretreatment rectal temperature were considered, respectively, as covariates, a significant (P < 0.05) depression of milk production and a significant (P < 0.05) increase in rectal temperature were observed one day following injection. These effects were small and short-lived. The stage of lactation, level of milk production, and choice of product may be used as decision-making tools to decrease milk production losses in vaccine-candidate cows. PMID:11665428

  8. Lactococcus lactis-based vaccines: current status and future perspectives.

    PubMed

    Bahey-El-Din, Mohammed; Gahan, Cormac G M

    2011-01-01

    Lactococcus lactis offers significant potential as a platform for the delivery of vaccines especially via mucosal routes of administration. The organism has an established history of safe use in the food industry and is highly amenable to genetic manipulation, with many systems available for efficient production of secreted and surface-expressed proteins. Here we describe the benefits of using this organism as a vaccine delivery platform and outline how L. lactis based antigen delivery may be improved. Finally we discuss the safe use of L. lactis vectors and outline the potential for use of biological containment systems and killed lactococcal preparations.

  9. 9 CFR 113.318 - Pseudorabies Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Pseudorabies Vaccine. 113.318 Section... Virus Vaccines § 113.318 Pseudorabies Vaccine. Pseudorabies Vaccine shall be prepared from virus-bearing... be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the...

  10. 9 CFR 113.318 - Pseudorabies Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Pseudorabies Vaccine. 113.318 Section... Virus Vaccines § 113.318 Pseudorabies Vaccine. Pseudorabies Vaccine shall be prepared from virus-bearing... be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the...

  11. 9 CFR 113.303 - Bluetongue Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bluetongue Vaccine. 113.303 Section... Virus Vaccines § 113.303 Bluetongue Vaccine. Bluetongue Vaccine shall be prepared from virus-bearing... be used for preparing the seeds for vaccine production. All serials of vaccine shall be prepared from...

  12. 9 CFR 113.303 - Bluetongue Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bluetongue Vaccine. 113.303 Section... Virus Vaccines § 113.303 Bluetongue Vaccine. Bluetongue Vaccine shall be prepared from virus-bearing... be used for preparing the seeds for vaccine production. All serials of vaccine shall be prepared from...

  13. 9 CFR 113.303 - Bluetongue Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bluetongue Vaccine. 113.303 Section... Virus Vaccines § 113.303 Bluetongue Vaccine. Bluetongue Vaccine shall be prepared from virus-bearing... be used for preparing the seeds for vaccine production. All serials of vaccine shall be prepared from...

  14. 9 CFR 113.318 - Pseudorabies Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Pseudorabies Vaccine. 113.318 Section... Virus Vaccines § 113.318 Pseudorabies Vaccine. Pseudorabies Vaccine shall be prepared from virus-bearing... be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the...

  15. 9 CFR 113.318 - Pseudorabies Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Pseudorabies Vaccine. 113.318 Section... Virus Vaccines § 113.318 Pseudorabies Vaccine. Pseudorabies Vaccine shall be prepared from virus-bearing... be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the...

  16. 9 CFR 113.303 - Bluetongue Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bluetongue Vaccine. 113.303 Section... Virus Vaccines § 113.303 Bluetongue Vaccine. Bluetongue Vaccine shall be prepared from virus-bearing... be used for preparing the seeds for vaccine production. All serials of vaccine shall be prepared from...

  17. 9 CFR 113.318 - Pseudorabies Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Pseudorabies Vaccine. 113.318 Section... Virus Vaccines § 113.318 Pseudorabies Vaccine. Pseudorabies Vaccine shall be prepared from virus-bearing... be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the...

  18. 9 CFR 113.303 - Bluetongue Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bluetongue Vaccine. 113.303 Section... Virus Vaccines § 113.303 Bluetongue Vaccine. Bluetongue Vaccine shall be prepared from virus-bearing... be used for preparing the seeds for vaccine production. All serials of vaccine shall be prepared from...

  19. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    PubMed

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.

  20. 9 CFR 113.326 - Avian Pox Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Avian Pox Vaccine. 113.326 Section 113... Vaccines § 113.326 Avian Pox Vaccine. Fowl Pox Vaccine and Pigeon Pox Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  1. 9 CFR 113.326 - Avian Pox Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Avian Pox Vaccine. 113.326 Section 113... Vaccines § 113.326 Avian Pox Vaccine. Fowl Pox Vaccine and Pigeon Pox Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  2. 9 CFR 113.326 - Avian Pox Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Avian Pox Vaccine. 113.326 Section 113... Vaccines § 113.326 Avian Pox Vaccine. Fowl Pox Vaccine and Pigeon Pox Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  3. 9 CFR 113.326 - Avian Pox Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Avian Pox Vaccine. 113.326 Section 113... Vaccines § 113.326 Avian Pox Vaccine. Fowl Pox Vaccine and Pigeon Pox Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  4. 9 CFR 113.326 - Avian Pox Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Avian Pox Vaccine. 113.326 Section 113... Vaccines § 113.326 Avian Pox Vaccine. Fowl Pox Vaccine and Pigeon Pox Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

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

    PubMed Central

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

    2013-01-01

    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

  6. 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).

  7. [Master files: less paper, more substance. Special rules for special medicines: Plasma Master File and Vaccine Antigen Master File].

    PubMed

    Seitz, Rainer; Haase, M

    2008-07-01

    The process of reviewing the European pharmaceutical legislation resulted in a codex, which contains two new instruments related to marketing authorisation of biological medicines: Plasma Master File (PMF) and Vaccine Antigen Master File (VAMF). In the manufacture of plasma derivatives (e. g. coagulation factors, albumin, immunoglobulins), usually the same starting material, i. e. a plasma pool, is used for several products. In the case of vaccines, the same active substance, i.e. vaccine antigen, may be included in several combination vaccine products. The intention behind the introduction of PMF and VAMF was to avoid unnecessary and redundant documentation, and to improve and harmonise assessment by means of procedures for certification of master files on the community level.

  8. Serum-free microcarrier based production of replication deficient Influenza vaccine candidate virus lacking NS1 using Vero cells

    PubMed Central

    2011-01-01

    Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1) gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM) were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the first time the production

  9. Bivalent rLP2086 (Trumenba®): Development of a well-characterized vaccine through commercialization.

    PubMed

    Sunasara, Khurram; Cundy, John; Srinivasan, Sriram; Evans, Brad; Sun, Weiqiang; Cook, Scott; Bortell, Eric; Farley, John; Griffin, Daniel; Bailey Piatchek, Michele; Arch-Douglas, Katherine

    2018-05-24

    The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation. Bivalent rLP2086 contains two rLP2086 antigens and is licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B in individuals 10-25years of age in the United States. This paper discusses the development of the manufacturing process of the two antigens for the purpose of making it amenable to any manufacturing facility. For the journey to commercialization, the operating model used to manage this highly accelerated program led to a framework that ensured "right the first time" execution, robust process characterization, and proactive process monitoring. This framework enabled quick problem identification and proactive resolutions, resulting in a robust control strategy for the commercial process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Experimental intramammary inoculation with Mycoplasma bovis in vaccinated and unvaccinated cows: effect on milk production and milk quality.

    PubMed Central

    Boothby, J T; Jasper, D E; Thomas, C B

    1986-01-01

    The effect of vaccination on milk production was evaluated in vaccinated and control cows experimentally challenged in two of four quarters with live Mycoplasma bovis. During the first three weeks after experimental challenge, six of eight unchallenged quarters on vaccinated cows and seven of eight unchallenged quarters on control cows became infected. Most of these quarters secreted normal milk, with negative California Mastitis Test scores and maintained normal milk production throughout most of the study (although some quarters on control cows remained infected). All challenged quarters became infected, had strong California Mastitis Test reactions, and had a drastic (greater than 85%) loss in milk production. Thereafter, four of eight challenged quarters on control cows remained infected, had mostly positive California Mastitis Test scores, produced mostly normal-appearing milk, and recovered some productive capabilities. By the end of the study no M. bovis could be recovered from challenged quarters on vaccinated cows and the milk appeared mostly normal. The California Mastitis Test scores on these quarters, however, remained elevated and milk production remained very low. PMID:3756674

  11. 9 CFR 113.304 - Feline Panleukopenia Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Feline Panleukopenia Vaccine. 113.304... Virus Vaccines § 113.304 Feline Panleukopenia Vaccine. Feline Panleukopenia Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  12. 9 CFR 113.304 - Feline Panleukopenia Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feline Panleukopenia Vaccine. 113.304... Virus Vaccines § 113.304 Feline Panleukopenia Vaccine. Feline Panleukopenia Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  13. 9 CFR 113.304 - Feline Panleukopenia Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Feline Panleukopenia Vaccine. 113.304... Virus Vaccines § 113.304 Feline Panleukopenia Vaccine. Feline Panleukopenia Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  14. 9 CFR 113.304 - Feline Panleukopenia Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Feline Panleukopenia Vaccine. 113.304... Virus Vaccines § 113.304 Feline Panleukopenia Vaccine. Feline Panleukopenia Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  15. 9 CFR 113.304 - Feline Panleukopenia Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Feline Panleukopenia Vaccine. 113.304... Virus Vaccines § 113.304 Feline Panleukopenia Vaccine. Feline Panleukopenia Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  16. 9 CFR 113.329 - Newcastle Disease Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Newcastle Disease Vaccine. 113.329... Virus Vaccines § 113.329 Newcastle Disease Vaccine. Newcastle Disease Vaccine shall be prepared from...) of this section shall be used for preparing the production seed virus for vaccine production. All...

  17. 9 CFR 113.314 - Feline Calicivirus Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Feline Calicivirus Vaccine. 113.314... Virus Vaccines § 113.314 Feline Calicivirus Vaccine. Feline Calicivirus Vaccine shall be prepared from... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  18. 9 CFR 113.329 - Newcastle Disease Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Newcastle Disease Vaccine. 113.329... Virus Vaccines § 113.329 Newcastle Disease Vaccine. Newcastle Disease Vaccine shall be prepared from...) of this section shall be used for preparing the production seed virus for vaccine production. All...

  19. 9 CFR 113.314 - Feline Calicivirus Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feline Calicivirus Vaccine. 113.314... Virus Vaccines § 113.314 Feline Calicivirus Vaccine. Feline Calicivirus Vaccine shall be prepared from... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  20. 9 CFR 113.329 - Newcastle Disease Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Newcastle Disease Vaccine. 113.329... Virus Vaccines § 113.329 Newcastle Disease Vaccine. Newcastle Disease Vaccine shall be prepared from...) of this section shall be used for preparing the production seed virus for vaccine production. All...

  1. 9 CFR 113.329 - Newcastle Disease Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Newcastle Disease Vaccine. 113.329... Virus Vaccines § 113.329 Newcastle Disease Vaccine. Newcastle Disease Vaccine shall be prepared from...) of this section shall be used for preparing the production seed virus for vaccine production. All...

  2. 9 CFR 113.314 - Feline Calicivirus Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Feline Calicivirus Vaccine. 113.314... Virus Vaccines § 113.314 Feline Calicivirus Vaccine. Feline Calicivirus Vaccine shall be prepared from... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  3. 9 CFR 113.314 - Feline Calicivirus Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Feline Calicivirus Vaccine. 113.314... Virus Vaccines § 113.314 Feline Calicivirus Vaccine. Feline Calicivirus Vaccine shall be prepared from... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  4. 9 CFR 113.314 - Feline Calicivirus Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Feline Calicivirus Vaccine. 113.314... Virus Vaccines § 113.314 Feline Calicivirus Vaccine. Feline Calicivirus Vaccine shall be prepared from... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  5. 9 CFR 113.329 - Newcastle Disease Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Newcastle Disease Vaccine. 113.329... Virus Vaccines § 113.329 Newcastle Disease Vaccine. Newcastle Disease Vaccine shall be prepared from...) of this section shall be used for preparing the production seed virus for vaccine production. All...

  6. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Sampling of biological products. 113.3 Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... Applicability § 113.3 Sampling of biological products. Each licensee and permittee shall furnish representative...

  7. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sampling of biological products. 113.3 Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... Applicability § 113.3 Sampling of biological products. Each licensee and permittee shall furnish representative...

  8. Production and dose determination of the Infection and Treatment Method (ITM) Muguga cocktail vaccine used to control East Coast fever in cattle.

    PubMed

    Patel, Ekta; Mwaura, Stephen; Kiara, Henry; Morzaria, Subhash; Peters, Andrew; Toye, Philip

    2016-03-01

    The Infection and Treatment Method (ITM) of vaccination against the apicomplexan parasite Theileria parva has been used since the early 1970s and is still the only commercially available vaccine to combat the fatal bovine disease, East Coast fever (ECF). The disease is tick-transmitted and results in annual economic losses of at least $300 million per year. While this vaccine technology has been available for over 40 years, few attempts have been made to standardize the production process and characterize the vaccine. The latest batch was produced in early 2008 at the International Livestock Research Institute (ILRI). The vaccine production involves the use of cattle free from parasites routinely monitored throughout the production process, and a pathogen-free tick colony. This paper describes the protocol used in the recent production, and the process improvements, including improved quality control tools, that had not been employed in previous ITM productions. The paper also describes the processes involved in determining the appropriate field dose, which involved a three-step in vivo study with various dilutions of the vaccine stabilate. The vaccine was shown to be safe and viable after production, and a suitable field dose was identified as 1 ml of a 1:100 dilution. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. 9 CFR 113.331 - Bursal Disease Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bursal Disease Vaccine. 113.331... Virus Vaccines § 113.331 Bursal Disease Vaccine. Bursal Disease Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  10. 9 CFR 113.330 - Marek's Disease Vaccines.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Marek's Disease Vaccines. 113.330... Virus Vaccines § 113.330 Marek's Disease Vaccines. Marek's disease vaccine shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. (a) The Master Seed...

  11. 9 CFR 113.330 - Marek's Disease Vaccines.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Marek's Disease Vaccines. 113.330... Virus Vaccines § 113.330 Marek's Disease Vaccines. Marek's disease vaccine shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. (a) The Master Seed...

  12. 9 CFR 113.330 - Marek's Disease Vaccines.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Marek's Disease Vaccines. 113.330... Virus Vaccines § 113.330 Marek's Disease Vaccines. Marek's disease vaccine shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. (a) The Master Seed...

  13. 9 CFR 113.331 - Bursal Disease Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bursal Disease Vaccine. 113.331... Virus Vaccines § 113.331 Bursal Disease Vaccine. Bursal Disease Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  14. 9 CFR 113.331 - Bursal Disease Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bursal Disease Vaccine. 113.331... Virus Vaccines § 113.331 Bursal Disease Vaccine. Bursal Disease Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  15. 9 CFR 113.331 - Bursal Disease Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bursal Disease Vaccine. 113.331... Virus Vaccines § 113.331 Bursal Disease Vaccine. Bursal Disease Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  16. 9 CFR 113.330 - Marek's Disease Vaccines.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Marek's Disease Vaccines. 113.330... Virus Vaccines § 113.330 Marek's Disease Vaccines. Marek's disease vaccine shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. (a) The Master Seed...

  17. 9 CFR 113.331 - Bursal Disease Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bursal Disease Vaccine. 113.331... Virus Vaccines § 113.331 Bursal Disease Vaccine. Bursal Disease Vaccine shall be prepared from virus... this section shall be used for preparing the production seed virus for vaccine production. All serials...

  18. 9 CFR 113.330 - Marek's Disease Vaccines.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Marek's Disease Vaccines. 113.330... Virus Vaccines § 113.330 Marek's Disease Vaccines. Marek's disease vaccine shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. (a) The Master Seed...

  19. Standardization and assessment of cell culture media quantities in roller poly ethylene terephthalate bottles employed in the industrial rabies viral vaccine production.

    PubMed

    Jagannathan, S; Chaansha, S; Rajesh, K; Santhiya, T; Charles, C; Venkataramana, K N

    2009-09-15

    Vero cells are utilized for production of rabies vaccine. This study deals with the optimize quantity media require for the rabies vaccine production in the smooth roller surface. The rabies virus (Pasteur vaccine strain) is infected to monolayer of the various experimented bottles. To analyze the optimal quantity of media for the production of rabies viral harvest during the process of Vero cell derived rabies vaccine. The trials are started from 200 to 400 mL (PTARV-1, PTARV-2, PTARV-3, PTARV-4 and PTARV-5). The samples are taken in an appropriate time intervals for analysis of In Process Quality Control (IPQC) tests. The collected viral harvests are further processed to rabies vaccine in a pilot level and in addition to scale up an industrial level. Based on the evaluation the PTARV-2 (250 mL) show highly encouraging results for the Vero cell derived rabies vaccine production.

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

    PubMed

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

    2009-11-01

    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. 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 conducted according to authoritative guidelines. Mice and gnotobiotic rats were intranasally immunized with clinical-grade pGJA-P/VAX with chitosan. Antibody levels of serum IgG and salivary SIgA were assessed by an enzyme-linked immunosorbent assay (ELISA), and caries activity was evaluated by the Keyes method. pGJA-P/VAX and pVAX1 prepared by a laboratory-scale commercial kit were used as controls. The production process proved to be scalable and reproducible. Impurities including host protein, residual RNA, genomic DNA and endotoxin in the purified plasmid were all under the limits of set specifications. Intranasal vaccination with clinical-grade pGJA-P/VAX induced higher serum IgG and salivary SIgA in both mice and gnotobiotic rats. While in the experimental caries model, the enamel (E), dentinal slight (Ds), and dentinal moderate (Dm) caries lesions were reduced by 21.1%, 33.0%, and 40.9%, respectively. The production process under GMP was efficient in preparing clinical-grade pGJA-P/VAX with high purity and intended effectiveness, thus facilitating future clinical trials for the anti-caries DNA vaccine.

  1. Military vaccines in today's environment.

    PubMed

    Schmaljohn, Connie S; Smith, Leonard A; Friedlander, Arthur M

    2012-08-01

    The US military has a long and highly distinguished record of developing effective vaccines against pathogens that threaten the armed forces. Many of these vaccines have also been of significant benefit to civilian populations around the world. The current requirements for force protection include vaccines against endemic disease threats as well as against biological warfare or bioterrorism agents, to include novel or genetically engineered threats. The cost of vaccine development and the modern regulatory requirements for licensing vaccines have strained the ability of the program to maintain this broad mission. Without innovative vaccine technologies, streamlined regulatory strategies, and coordinating efforts for use in civilian populations where appropriate, the military vaccine development program is in jeopardy.

  2. An oral microjet vaccination system elicits antibody production in rabbits.

    PubMed

    Aran, Kiana; Chooljian, Marc; Paredes, Jacobo; Rafi, Mohammad; Lee, Kunwoo; Kim, Allison Y; An, Jeanny; Yau, Jennifer F; Chum, Helen; Conboy, Irina; Murthy, Niren; Liepmann, Dorian

    2017-03-08

    Noninvasive immunization technologies have the potential to revolutionize global health by providing easy-to-administer vaccines at low cost, enabling mass immunizations during pandemics. Existing technologies such as transdermal microneedles are costly, deliver drugs slowly, and cannot generate mucosal immunity, which is important for optimal immunity against pathogens. We present a needle-free microjet immunization device termed MucoJet, which is a three-dimensional microelectromechanical systems-based drug delivery technology. MucoJet is administered orally, placed adjacent to the buccal tissue within the oral cavity, and uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine. We show that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer in silico, in porcine buccal tissue ex vivo, and in rabbits in vivo. Rabbits treated with ovalbumin by MucoJet delivery have antibody titers of anti-ovalbumin immunoglobulins G and A in blood serum and buccal tissue, respectively, that are three orders of magnitude higher than rabbits receiving free ovalbumin delivered topically by a dropper in the buccal region. MucoJet has the potential to accelerate the development of noninvasive oral vaccines, given its ability to elicit antibody production that is detectable locally in the buccal tissue and systemically via the circulation. Copyright © 2017, American Association for the Advancement of Science.

  3. Oral vaccination with an adenovirus-vectored vaccine protects against botulism

    PubMed Central

    Chen, Shan; Xu, Qingfu; Zeng, Mingtao

    2013-01-01

    We have previously shown that an adenovirus vectored vaccine delivered intramuscularly or intranasally was effective in protection against botulism in a mouse model. The adenoviral vector encodes a human codon-optimized heavy chain C-fragment (HC50) of botulinum neurotoxin type C (BoNT/C). Here, we evaluate the same vaccine candidate as an oral vaccine against BoNT/C in a mouse model. To elicit protective immunity, the mice were orally vaccinated with a single dose of 1×104 to 1×107 plaque forming units (pfu) of the adenoviral vector. The immune sera, collected six weeks after oral vaccination with 2×107 pfu adenovirus, has shown an ability to neutralize the biological activity of BoNT/C in vitro. Additionally, animals receiving a single dose of 2×106 pfu adenovirus or greater were completely protected against challenge with 100×MLD50 of BoNT/C. The data demonstrated the feasibility to develop an adenovirus-based oral vaccine against botulism. PMID:23295065

  4. Avian influenza vaccines and vaccination in birds.

    PubMed

    Capua, Ilaria; Alexander, Dennis J

    2008-09-12

    Although the use of vaccines against avian influenza viruses in birds has been discouraged over the years, the unprecedented occurrence of outbreaks caused by avian influenza (AI) viruses in recent times has required review of this policy. A variety of products are now available on the market, ranging from inactivated conventional to live recombinant products. The general consensus on the use of vaccination is that if complying to GMP standards and properly administered, birds will be more resistant to field challenge and will exhibit reduced shedding levels in case of infection. However, viral circulation may still occur in a clinically healthy vaccinated population. This may result in an endemic situation and in the emergence of antigenic variants. In order to limit these risks, monitoring programmes enabling the detection of field exposure in vaccinated populations are recommended by international organisations and are essential to allow the continuation of international trade. Adequate management of a vaccination campaign, including monitoring, improved biosecurity and restriction is essential for the success of any control program for AI.

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

    PubMed

    Frey, Joachim

    2007-07-26

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

  6. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

    PubMed Central

    van der Sanden, Sabine M. G.; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C.; Brooks, Paula; O'Donnell, Jason; Jones, Les P.; Brown, Cedric; Tompkins, S. Mark; Karpilow, Jon; Tripp, Ralph A.

    2015-01-01

    ABSTRACT Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. IMPORTANCE Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines

  7. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game.

    PubMed

    van der Sanden, Sabine M G; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C; Brooks, Paula; O'Donnell, Jason; Jones, Les P; Brown, Cedric; Tompkins, S Mark; Oberste, M Steven; Karpilow, Jon; Tripp, Ralph A

    2016-02-15

    Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work

  8. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared...

  9. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared...

  10. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared...

  11. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared...

  12. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared...

  13. Development of a highly sensitive PCR/DNA chip method to detect mycoplasmas in a veterinary modified live vaccine.

    PubMed

    Mbelo, Sylvie; Gay, Virginie; Blanchard, Stephanie; Abachin, Eric; Falque, Stephanie; Lechenet, Jacques; Poulet, Hervé; de Saint-Vis, Blandine

    2018-05-09

    Mycoplasmas are potential contaminants that introduce undesirable changes in mammalian cell cultures. They frequently contaminate cell substrates and other starting materials used for manufacturing cell-derived biologics, such as vaccines and pharmaceutical products. Mycoplasma purity testing of live vaccines, active ingredients, raw material, and seed lots is required during vaccine production. Previously, testing using a time-consuming, costly 28-day culture assay, which lacks sensitivity for species that do not grow in culture, was required in the European Pharmacopoeia (Ph. Eur). But now nucleic acid amplification techniques (NATs) can be used. NATs provide rapid results and are sensitive. We evaluated the sensitivity and specificity of a commercially-available NAT to detect individual mycoplasma DNA in a veterinary modified live vaccine using five reference strains recommended by the Ph. Eur. Our results showed that this NAT-based method can be used to detect mycoplasma in spiked live vaccine, without interference from the vaccine components, with a limit of detection of 10 CFU/mL, as required by the Ph. Eur. Its specificity was demonstrated since no mycoplasmas were detected in non-spiked vaccine. This method is undergoing validation as a replacement for the conventional culture method in the production of veterinary live vaccines. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. What vaccine product attributes do immunization program stakeholders value? Results from interviews in six low- and middle-income countries.

    PubMed

    Kristensen, Debra D; Bartholomew, Kate; Villadiego, Shirley; Lorenson, Kristina

    2016-12-07

    This study attempts to capture the opinions of stakeholders working in immunization programs in low- and middle-income countries to understand how vaccine products could be improved to better meet their needs and to obtain feedback on specific vaccine product attributes including the number of doses per container and ease of preparing a dose for administration. We also reviewed how procurement decisions are made within immunization programs. Semi-structured interviews were undertaken with 158 immunization stakeholders in Brazil, China, India, Peru, the Philippines, and Tanzania. Interviewees included national decision-makers and advisors involved in vaccine-purchasing decisions (n=30), national Expanded Programme on Immunization managers (n=6), and health and logistics personnel at national, subnational, and health-facility levels (n=122). Immunization stakeholders at all levels of the supply chain valued vaccine product attributes that prevent heat damage, decrease vaccine wastage, and simplify delivery. Minimizing the time required to prepare a dose is especially valued by those closest to the work of actually administering vaccines. Respondents appreciated the benefits of lower-multidose presentations on reducing wastage but seemed to prefer single-dose vials even more. They also expressed concern about the need for training and the potential for confusion and vial contamination if opened vials of liquid preservative-free vaccines are not handled properly. Procurement decision-making processes varied widely between countries, though most relied heavily on international agencies and vaccine manufacturers for information. Copyright © 2016. Published by Elsevier Ltd.

  15. An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock

    PubMed Central

    Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G

    2008-01-01

    Background Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy. Methods As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures. Results The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B. Conclusion Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component. The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product. PMID:18768085

  16. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    PubMed

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

    2016-04-02

    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  17. Hepatitis A Vaccine

    MedlinePlus

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Why get vaccinated against hepatitis A?Hepatitis A is a serious liver disease. It is caused by the hepatitis A virus (HAV). HAV is spread from ...

  18. Designing vaccines based on biology of human dendritic cell subsets

    PubMed Central

    Palucka, Karolina; Banchereau, Jacques; Mellman, Ira

    2010-01-01

    The effective vaccines developed against a variety of infectious agents, including polio, measles and Hepatitis B, represent major achievements in medicine. These vaccines, usually composed of microbial antigens, are often associated with an adjuvant that activates dendritic cells (DCs). Many infectious diseases are still in need of an effective vaccine including HIV, malaria, hepatitis C and tuberculosis. In some cases, the induction of cellular rather than humoral responses may be more important as the goal is to control and eliminate the existing infection rather than to prevent it. Our increased understanding of the mechanisms of antigen presentation, particularly with the description of DC subsets with distinct functions, as well as their plasticity in responding to extrinsic signals, represent opportunities to develop novel vaccines. In addition, we foresee that this increased knowledge will permit us to design vaccines that will reprogram the immune system to intervene therapeutically in cancer, allergy and autoimmunity. PMID:21029958

  19. FDA Regulation of Follow-On Biologics

    DTIC Science & Technology

    2009-02-24

    opening a pathway for the approval of follow-on biologics. A biologic is a preparation, such as a drug or a vaccine , that is made from living...2006 Drug Trend Report, April 2006, p. 38. C Biologic vs. Follow-on Biologic A biologic is a preparation, such as a drug or a vaccine , that is...doc9496/s1695.pdf. 19 Thijs J. Giezen, Aukje K. Mantel-Teeuwisse, and Sabine M. J. M. Straus, et al., “Safety-related regulatory actions for biologicals

  20. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Human Vaccines & Immunotherapeutics: News

    PubMed Central

    Riedmann, Eva M

    2013-01-01

    Vaccinating boys against HPV to reduce cancer rates across the sexes New melanoma vaccine contains natural product from marine sponges Impact of Hib conjugate vaccines in developing countries Electronic Health Records to keep track of immunization status Pregnant women urged to get whooping cough vaccination New nano-coating developed to preserve vaccines Alternative approach to creating a universal flu vaccine New modular vaccine design: MAPS technology PMID:24051387

  2. DHB Task Force Review of DoD Biodefense Infrastructure and Biological Research Portfolio

    DTIC Science & Technology

    2009-04-29

    Center and Biological Defense and Research Directorate (BORD) biodefense research portfolio includes vaccines, molecular diagnostics , genomics, and...human monoclonal antibodies, and innate immune agonists); molecular diagnostics (including recombinant reagents, assay development, reagent production

  3. Near-Infrared Laser Adjuvant for Influenza Vaccine

    PubMed Central

    Kashiwagi, Satoshi; Yuan, Jianping; Forbes, Benjamin; Hibert, Mathew L.; Lee, Eugene L. Q.; Whicher, Laura; Goudie, Calum; Yang, Yuan; Chen, Tao; Edelblute, Beth; Collette, Brian; Edington, Laurel; Trussler, James; Nezivar, Jean; Leblanc, Pierre; Bronson, Roderick; Tsukada, Kosuke; Suematsu, Makoto; Dover, Jeffrey; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C.

    2013-01-01

    Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants. PMID:24349390

  4. 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

  5. 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

  6. 9 CFR 113.308 - Encephalomyelitis Vaccine, Venezuelan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Encephalomyelitis Vaccine, Venezuelan... REQUIREMENTS Live Virus Vaccines § 113.308 Encephalomyelitis Vaccine, Venezuelan. Encephalomyelitis Vaccine... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  7. 9 CFR 113.308 - Encephalomyelitis Vaccine, Venezuelan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Encephalomyelitis Vaccine, Venezuelan... REQUIREMENTS Live Virus Vaccines § 113.308 Encephalomyelitis Vaccine, Venezuelan. Encephalomyelitis Vaccine... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  8. 9 CFR 113.308 - Encephalomyelitis Vaccine, Venezuelan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Encephalomyelitis Vaccine, Venezuelan... REQUIREMENTS Live Virus Vaccines § 113.308 Encephalomyelitis Vaccine, Venezuelan. Encephalomyelitis Vaccine... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  9. 9 CFR 113.308 - Encephalomyelitis Vaccine, Venezuelan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Encephalomyelitis Vaccine, Venezuelan... REQUIREMENTS Live Virus Vaccines § 113.308 Encephalomyelitis Vaccine, Venezuelan. Encephalomyelitis Vaccine... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  10. 9 CFR 113.308 - Encephalomyelitis Vaccine, Venezuelan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Encephalomyelitis Vaccine, Venezuelan... REQUIREMENTS Live Virus Vaccines § 113.308 Encephalomyelitis Vaccine, Venezuelan. Encephalomyelitis Vaccine... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of...

  12. [Guidelines for vaccination of immunocompromised individuals].

    PubMed

    Wiedermann, Ursula; Sitte, Harald H; Burgmann, Heinz; Eser, Alexander; Falb, Petra; Holzmann, Heidemarie; Kitchen, Maria; Köller, Marcus; Kollaritsch, Herwig; Kundi, Michael; Lassmann, Hans; Mutz, Ingomar; Pickl, Winfried F; Riedl, Elisabeth; Sibilia, Maria; Thalhammer, Florian; Tucek, Barbara; Zenz, Werner; Zwiauer, Karl

    2016-08-01

    Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.

  13. [Paediatric Invasive Pneumococcal Disease Before Universal Vaccination: 1995 - 2015].

    PubMed

    Ferreira, Muriel; Oliveira, Henrique; Silva, Nuno Costa; Januário, Luís; Rodrigues, Fernanda

    2017-06-30

    Pneumococcal conjugate vaccine was introduced in the private market in Portugal in 2001, reaching over the years a moderately high coverage. In July 2015, it was included in the National Immunisation Program. The aim of this study was to characterize invasive pneumococcal disease in a pediatric hospital before universal use of the vaccine. Retrospective analysis of medical records of all children with Streptococcus pneumoniae identified by culture and/or molecular biology (available since 2008), in products obtained from sterile sites, from January 1995 to June 2015. We evaluated demographic, clinical and microbiological data. Serotype results are available since 2004. Over those 20 years, 112 invasive pneumococcal disease cases were identified, with a median age of 15 months (1 month - 15 years). The median number of cases /year was 4, the highest between 2001 - 2002 (8/year) and 2007 - 2012 (7 - 11/year). The identification occurred mostly in blood culture (72), cerebrospinal fluid (24), pleural fluid (11) an others (5). The most frequent diagnoses were pneumonia (38%), occult bacteraemia (34%) and meningitis (21%). Over the period under review, there was an increase of pneumonia and slight increase of OB, with meningitis cases remaining relatively unchanged. In the last two decades, there was no reduction in the number of cases of invasive pneumococcal disease. There was an increase in isolates from pneumonia and occult bacteraemia that might be due to the introduction of molecular biological methods for Streptococcus pneumoniae detection. Vaccine serotypes were predominant. This retrospective analysis before universal vaccination will contribute to evaluate the impact of vaccination in the Portuguese pediatric population.

  14. Private-sector vaccine purchase costs and insurer payments: a disincentive for using combination vaccines?

    PubMed

    Clark, Sarah J; Cowan, Anne E; Freed, Gary L

    2011-04-01

    Combination vaccines have been endorsed as a means to decrease the number of injections needed to complete the childhood immunization schedule, yet anecdotal reports suggest that private providers lose money on combination vaccines. The objective of this study was to determine whether practices purchasing combination vaccines had significantly different vaccine costs and reimbursement compared to practices that were not purchasing combination vaccines. Using cross-sectional purchase and insurer payment data collected from a targeted sample of private practices in five US states, we calculated the average total vaccine cost and reimbursement across the childhood immunization schedule. The average vaccine purchase cost across the childhood schedule was significantly higher for practices using a combined vaccine with diphtheria, tetanus, acellular pertussis vaccine, inactivated polio vaccine, and Hepatitis B vaccine (DTaP-IPV-HepB) than for practices using either separate vaccine products or a combined vaccine with Haemophilus influenzae, type b vaccine and Hepatitis B vaccine (Hib-HepB). The average insurer payment for vaccine administration across the childhood schedule was significantly lower for practices using DTaP-IPV-HepB combination vaccine than for practices using separate vaccine products. This study appears to validate anecdotal reports that vaccine purchase costs and insurer payment for combination vaccines can have a negative financial impact for practices that purchase childhood vaccines.

  15. Continuous cell lines from the Muscovy duck as potential replacement for primary cells in the production of avian vaccines.

    PubMed

    Jordan, Ingo; John, Katrin; Höwing, Kristin; Lohr, Verena; Penzes, Zoltán; Gubucz-Sombor, Erzsébet; Fu, Yan; Gao, Peng; Harder, Timm; Zádori, Zoltán; Sandig, Volker

    2016-01-01

    Veterinary vaccines contribute to food security, interrupt zoonotic transmissions, and help to maintain overall health in livestock. Although vaccines are usually cost-effective, their adoption depends on a multitude of factors. Because poultry vaccines are usually given to birds with a short life span, very low production cost per dose is one important challenge. Other hurdles are to ensure a consistent and reliable supply of very large number of doses, and to have flexible production processes to accommodate a range of different pathogens and dosage requirements. Most poultry vaccines are currently being produced on primary avian cells derived from chicken or waterfowl embryos. This production system is associated with high costs, logistic complexities, rigid intervals between harvest and production, and supply limitations. We investigated whether the continuous cell lines Cairina retina and CR.pIX may provide a substrate independent of primary cell cultures or embryonated eggs. Viruses examined for replication in these cell lines are strains associated with, or contained in vaccines against egg drop syndrome, Marek's disease, Newcastle disease, avian influenza, infectious bursal disease and Derzsy's disease. Each of the tested viruses required the development of unique conditions for replication that are described here and can be used to generate material for in vivo efficacy studies and to accelerate transfer of the processes to larger production volumes.

  16. 9 CFR 113.325 - Avian Encephalomyelitis Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Avian Encephalomyelitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.325 Avian Encephalomyelitis Vaccine. Avian Encephalomyelitis Vaccine... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  17. 9 CFR 113.310 - Bovine Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bovine Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.310 Bovine Rhinotracheitis Vaccine. Bovine Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  18. 9 CFR 113.310 - Bovine Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bovine Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.310 Bovine Rhinotracheitis Vaccine. Bovine Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  19. 9 CFR 113.315 - Feline Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feline Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.315 Feline Rhinotracheitis Vaccine. Feline Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  20. 9 CFR 113.325 - Avian Encephalomyelitis Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Avian Encephalomyelitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.325 Avian Encephalomyelitis Vaccine. Avian Encephalomyelitis Vaccine... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  1. 9 CFR 113.315 - Feline Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Feline Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.315 Feline Rhinotracheitis Vaccine. Feline Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  2. 9 CFR 113.315 - Feline Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Feline Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.315 Feline Rhinotracheitis Vaccine. Feline Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  3. 9 CFR 113.315 - Feline Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Feline Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.315 Feline Rhinotracheitis Vaccine. Feline Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  4. 9 CFR 113.325 - Avian Encephalomyelitis Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Avian Encephalomyelitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.325 Avian Encephalomyelitis Vaccine. Avian Encephalomyelitis Vaccine... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  5. 9 CFR 113.315 - Feline Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Feline Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.315 Feline Rhinotracheitis Vaccine. Feline Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  6. 9 CFR 113.325 - Avian Encephalomyelitis Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Avian Encephalomyelitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.325 Avian Encephalomyelitis Vaccine. Avian Encephalomyelitis Vaccine... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  7. 9 CFR 113.310 - Bovine Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bovine Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.310 Bovine Rhinotracheitis Vaccine. Bovine Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  8. 9 CFR 113.310 - Bovine Rhinotracheitis Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bovine Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.310 Bovine Rhinotracheitis Vaccine. Bovine Rhinotracheitis Vaccine shall... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  9. 9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bovine Virus Diarrhea Vaccine. 113.311... Virus Vaccines § 113.311 Bovine Virus Diarrhea Vaccine. Bovine Virus Diarrhea Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  10. 9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bovine Virus Diarrhea Vaccine. 113.311... Virus Vaccines § 113.311 Bovine Virus Diarrhea Vaccine. Bovine Virus Diarrhea Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  11. 9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bovine Virus Diarrhea Vaccine. 113.311... Virus Vaccines § 113.311 Bovine Virus Diarrhea Vaccine. Bovine Virus Diarrhea Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  12. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  13. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  14. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  15. 9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bovine Virus Diarrhea Vaccine. 113.311... Virus Vaccines § 113.311 Bovine Virus Diarrhea Vaccine. Bovine Virus Diarrhea Vaccine shall be prepared..., and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  16. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  17. Potential large scale production of meningococcal vaccines by stable overexpression of fHbp in the rice seeds.

    PubMed

    Ma, Jian; Wang, Yunpeng; Xu, Nuo; Jin, Libo; Liu, Jia; Xing, Shaochen; Li, Xiaokun

    2018-06-25

    Factor H binding protein (fHbp) is the most promising vaccine candidate against serogroup B of Neisseria meningitidis which is a major cause of morbidity and mortality in children. In order to facilitate large scale production of a commercial vaccine, we previously used transgenic Arabidopsis thaliana, but plant-derived fHbp is still far away from a commercial vaccine due to less biomass production. Herein, we presented an alternative route for the production of recombinant fHbp from the seeds of transgenic rice. The OsrfHbp gene encoding recombinant fHbp fused protein was introduced into the genome of rice via Agrobacterium-mediated transformation. The both stable integration and transcription of the foreign OsrfHbp were confirmed by Southern blotting and RT-PCR analysis respectively. Further, the expression of fHbp protein was measured by immunoblotting analysis and quantified by ELISA. The results indicated that fHbp was successfully expressed and the highest yield of fHbp was 0.52 ± 0.03% of TSP in the transgenic rice seeds. The purified fHbp protein showed good antigenicity and immunogenicity in the animal model. The results of this experiment offer a novel approach for large-scale production of plant-derived commercial vaccine fHbp. Copyright © 2018. Published by Elsevier Inc.

  18. Intrathecal antibody production in two cases of yellow fever vaccine associated neurotropic disease in Argentina.

    PubMed

    Pires-Marczeski, Fanny Clara; Martinez, Valeria Paula; Nemirovsky, Corina; Padula, Paula Julieta

    2011-12-01

    During the period 2007-2008 several epizootics of Yellow fever with dead of monkeys occurred in southeastern Brasil, Paraguay, and northeastern Argentina. In 2008 after a Yellow fever outbreak an exhaustive prevention campaign took place in Argentina using 17D live attenuated Yellow fever vaccine. This vaccine is considered one of the safest live virus vaccines, although serious adverse reactions may occur after vaccination, and vaccine-associated neurotropic disease are reported rarely. The aim of this study was to confirm two serious adverse events associated to Yellow fever vaccine in Argentina, and to describe the analysis performed to assess the origin of specific IgM against Yellow fever virus (YFV) in cerebrospinal fluid (CSF). Both cases coincided with the Yellow fever vaccine-associated neurotropic disease case definition, being clinical diagnosis longitudinal myelitis (case 1) and meningoencephalitis (case 2). Specific YFV antibodies were detected in CSF and serum samples in both cases by IgM antibody-capture ELISA. No other cause of neurological disease was identified. In order to obtain a conclusive diagnosis of central nervous system (CNS) infection the IgM antibody index (AI(IgM) ) was calculated. High AI(IgM) values were found in both cases indicating intrathecal production of antibodies and, therefore, CNS post-vaccinal YFV infection could be definitively associated to YFV vaccination. Copyright © 2011 Wiley Periodicals, Inc.

  19. Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process.

    PubMed

    George, Meena; Farooq, Masiha; Dang, Thi; Cortes, Bernadette; Liu, Jonathan; Maranga, Luis

    2010-08-15

    The majority of influenza vaccines are manufactured using embryonated hens' eggs. The potential occurrence of a pandemic outbreak of avian influenza might reduce or even eliminate the supply of eggs, leaving the human population at risk. Also, the egg-based production technology is intrinsically cumbersome and not easily scalable to provide a rapid worldwide supply of vaccine. In this communication, the production of a cell culture (Madin-Darby canine kidney (MDCK)) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process using a novel Single Use Bioreactor (SUB) is presented. The cell culture and virus infection was maintained in a disposable stirred tank reactor with PID control of pH, DO, agitation, and temperature, similar to traditional glass or stainless steel bioreactors. The application of this technology was tested using MDCK cells grown on microcarriers in proprietary serum free medium and infection with 2006/2007 seasonal LAIV strains at 25-30 L scale. The MDCK cell growth was optimal at the agitation rate of 100 rpm. Optimization of this parameter allowed the cells to grow at a rate similar to that achieved in the conventional 3 L glass stirred tank bioreactors. Influenza vaccine virus strains, A/New Caledonia/20/99 (H1N1 strain), A/Wisconsin/67/05 (H3N2 strain), and B/Malaysia/2506/04 (B strain) were all successfully produced in SUB with peak virus titers > or =8.6 log(10) FFU/mL. This result demonstrated that more than 1 million doses of vaccine can be produced through one single run of a small bioreactor at the scale of 30 L and thus provided an alternative to the current vaccine production platform with fast turn-around and low upfront facility investment, features that are particularly useful for emerging and developing countries and clinical trial material production.

  20. The global fight to develop antipoverty vaccines in the anti-vaccine era.

    PubMed

    Hotez, Peter J

    2018-02-02

    Antipoverty vaccines are the vaccines targeting a group of approximately 20 neglected tropical diseases (NTDs), as currently defined by the World Health Organization (WHO). The "antipoverty" moniker refers to the fact that NTDs trap populations in poverty due to their chronic and deleterious effects on child intellect and worker productivity. Therefore, NTD vaccines can be expected to promote both global health and economic advancement. Unfortunately, antipoverty vaccine development has lagged behind vaccines for major childhood infections and pandemic threats, despite evidence for their cost-effectiveness and cost-savings. Currently, the only licensed vaccines for NTDs include those for yellow fever, dengue, and rabies, although several other NTD vaccines for hookworm disease, schistosomiasis, leishmaniasis, and Zika and Ebola virus infections are in different stages of clinical development, while others are at the preclinical development stage. With the exception of the viral NTD vaccines there so far has been minimal industry interest in the antipoverty vaccines, leaving their development to a handful of non-profit product development partnerships. The major scientific and geopolitical hurdles to antipoverty vaccine development are discussed, including a rising antivaccine ("antivax") movement now entering highly populated low- and middle-income countries.

  1. 9 CFR 113.312 - Rabies Vaccine, Live Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  2. 9 CFR 113.312 - Rabies Vaccine, Live Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  3. 9 CFR 113.312 - Rabies Vaccine, Live Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  4. 9 CFR 113.312 - Rabies Vaccine, Live Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

  5. 9 CFR 113.328 - Fowl Laryngotracheitis Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Fowl Laryngotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.328 Fowl Laryngotracheitis Vaccine. Fowl Laryngotracheitis Vaccine shall... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  6. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of...

  7. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of...

  8. 9 CFR 113.328 - Fowl Laryngotracheitis Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Fowl Laryngotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.328 Fowl Laryngotracheitis Vaccine. Fowl Laryngotracheitis Vaccine shall... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  9. 9 CFR 113.328 - Fowl Laryngotracheitis Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Fowl Laryngotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.328 Fowl Laryngotracheitis Vaccine. Fowl Laryngotracheitis Vaccine shall... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  10. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of...

  11. 9 CFR 113.328 - Fowl Laryngotracheitis Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Fowl Laryngotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.328 Fowl Laryngotracheitis Vaccine. Fowl Laryngotracheitis Vaccine shall... vaccine production. All serials shall be prepared from the first through the fifth passage from the Master...

  12. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of...

  13. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of...

  14. 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

  15. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  16. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  17. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  18. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  19. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for vaccine...

  20. 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

  1. Mixed treatment comparison meta-analysis of porcine circovirus type 2 (PCV2) vaccines used in piglets.

    PubMed

    da Silva, N; Carriquiry, A; O'Neill, K; Opriessnig, T; O'Connor, A M

    2014-12-01

    Porcine circovirus type 2 (PCV2) vaccination is globally one of the most commonly used intervention strategies in growing pigs since several products became commercially available in 2006. While multiple trials have described the efficacy of individual PCV2 vaccines relative to non-vaccination, few studies provide product-to-product comparisons of efficacy. Given the well-documented efficacy of PCV2 vaccines, information about the comparative efficacy of available vaccines is more relevant to producers and veterinarians than comparison to non-vaccination. The objective of this study was to provide comparative estimates of changes in average daily gain effect associated with the use of the commercially available PCV2 vaccines. PubMed, CAB Abstracts, AGRICOLA, the USA Department of Agriculture Center for Veterinary Biologics database of licenses and provisions, and the proceedings of the Annual Meeting of the American Association of Swine Veterinarians, the Allen D. Leman Swine Conference, the Iowa State University Swine Disease Conference for Swine Practitioners, and the International Pig Veterinary Society Congress were used as the sources of information. Trials of licensed PCV2 vaccines administered according to manufacturers' specifications to intensively raised piglets with a known herd porcine reproductive and respiratory syndrome virus (PRRSV) status were considered relevant to the meta-analysis. Relevant studies had to report average daily gain (ADG) from weaning to finish and PCV2 infection had to be naturally occurring. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Vaccines in a hurry.

    PubMed

    Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben

    2009-05-26

    Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

  3. Biotechnology and genetic engineering in the new drug development. Part II. Monoclonal antibodies, modern vaccines and gene therapy.

    PubMed

    Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

    2013-01-01

    Monoclonal antibodies, modern vaccines and gene therapy have become a major field in modern biotechnology, especially in the area of human health and fascinating developments achieved in the past decades are impressive examples of an interdisciplinary interplay between medicine, biology and engineering. Among the classical products from cells one can find viral vaccines, monoclonal antibodies, and interferons, as well as recombinant therapeutic proteins. Gene therapy opens up challenging new areas. In this review, a definitions of these processes are given and fields of application and products, as well as the future prospects, are discussed.

  4. Developing vaccines for an aging population.

    PubMed

    Black, Steven; De Gregorio, Ennio; Rappuoli, Rino

    2015-04-01

    The demographics of the world's population are changing, with many adults now surviving into their 80s. With this change comes the need to protect the aging and other underserved populations not only against infectious diseases but also against cancer and other chronic conditions. New technologies derived from recent advances in the fields of immunology, structural biology, synthetic biology, and genomics have brought a revolution in the vaccine field. Among them, vaccine adjuvants have the potential to harness the immune system to provide protection against new types of diseases, improve protection in young children, and expand this protection to adults and the elderly. However, in order to do so we need also to overcome the nontechnical challenges that could limit the implementation of innovative vaccines, including controversies regarding the safety of adjuvants, increasing regulatory complexity, the inadequate methods used to assess the value of novel vaccines, and the resulting industry alienation from future investment. This Perspective summarizes the outcome of a recent multidisciplinary symposium entitled "Enhancing Vaccine Immunity and Value," held in Siena, Italy, in July 2014, that addressed two related questions: how to improve vaccine efficacy by using breakthrough technologies and how to capture the full potential of novel vaccines. Copyright © 2015, American Association for the Advancement of Science.

  5. Veterinary vaccine nanotechnology: pulmonary and nasal delivery in livestock animals.

    PubMed

    Calderon-Nieva, Daniella; Goonewardene, Kalhari Bandara; Gomis, Susantha; Foldvari, Marianna

    2017-08-01

    Veterinary vaccine development has several similarities with human vaccine development to improve the overall health and well-being of species. However, veterinary goals lean more toward feasible large-scale administration methods and low cost to high benefit immunization. Since the respiratory mucosa is easily accessible and most infectious agents begin their infection cycle at the mucosa, immunization through the respiratory route has been a highly attractive vaccine delivery strategy against infectious diseases. Additionally, vaccines administered via the respiratory mucosa could lower costs by removing the need of trained medical personnel, and lowering doses yet achieving similar or increased immune stimulation. The respiratory route often brings challenges in antigen delivery efficiency with enough potency to induce immunity. Nanoparticle (NP) technology has been shown to enhance immune activation by producing higher antibody titers and protection. Although specific mechanisms between NPs and biological membranes are still under investigation, physical parameters such as particle size and shape, as well as biological tissue distribution including mucociliary clearance influence the protection and delivery of antigens to the site of action and uptake by target cells. For respiratory delivery, various biomaterials such as mucoadhesive polymers, lipids, and polysaccharides have shown enhanced antibody production or protection in comparison to antigen alone. This review presents promising NPs administered via the nasal or pulmonary routes for veterinary applications specifically focusing on livestock animals including poultry.

  6. Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines).

    PubMed

    Doroshenko, Alexander; Halperin, Scott A

    2009-06-01

    Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.

  7. Preventable mix-ups of tuberculin and vaccines: reports to the US Vaccine and Drug Safety Reporting Systems.

    PubMed

    Chang, Soju; Pool, Vitali; O'Connell, Kathryn; Polder, Jacquelyn A; Iskander, John; Sweeney, Colleen; Ball, Robert; Braun, M Miles

    2008-01-01

    Errors involving the mix-up of tuberculin purified protein derivative (PPD) and vaccines leading to adverse reactions and unnecessary medical management have been reported previously. To determine the frequency of PPD-vaccine mix-ups reported to the US Vaccine Adverse Event Reporting System (VAERS) and the Adverse Event Reporting System (AERS), characterize adverse events and clusters involving mix-ups and describe reported contributory factors. We reviewed AERS reports from 1969 to 2005 and VAERS reports from 1990 to 2005. We defined a mix-up error event as an incident in which a single patient or a cluster of patients inadvertently received vaccine instead of a PPD product or received a PPD product instead of vaccine. We defined a cluster as inadvertent administration of PPD or vaccine products to more than one patient in the same facility within 1 month. Of 115 mix-up events identified, 101 involved inadvertent administration of vaccines instead of PPD. Product confusion involved PPD and multiple vaccines. The annual number of reported mix-ups increased from an average of one event per year in the early 1990s to an average of ten events per year in the early part of this decade. More than 240 adults and children were affected and the majority reported local injection site reactions. Four individuals were hospitalized (all recovered) after receiving the wrong products. Several patients were inappropriately started on tuberculosis prophylaxis as a result of a vaccine local reaction being interpreted as a positive tuberculin skin test. Reported potential contributory factors involved both system factors (e.g. similar packaging) and human errors (e.g. failure to read label before product administration). To prevent PPD-vaccine mix-ups, proper storage, handling and administration of vaccine and PPD products is necessary.

  8. Development of a candidate reference material for adventitious virus detection in vaccine and biologicals manufacturing by deep sequencing

    PubMed Central

    Mee, Edward T.; Preston, Mark D.; Minor, Philip D.; Schepelmann, Silke; Huang, Xuening; Nguyen, Jenny; Wall, David; Hargrove, Stacey; Fu, Thomas; Xu, George; Li, Li; Cote, Colette; Delwart, Eric; Li, Linlin; Hewlett, Indira; Simonyan, Vahan; Ragupathy, Viswanath; Alin, Voskanian-Kordi; Mermod, Nicolas; Hill, Christiane; Ottenwälder, Birgit; Richter, Daniel C.; Tehrani, Arman; Jacqueline, Weber-Lehmann; Cassart, Jean-Pol; Letellier, Carine; Vandeputte, Olivier; Ruelle, Jean-Louis; Deyati, Avisek; La Neve, Fabio; Modena, Chiara; Mee, Edward; Schepelmann, Silke; Preston, Mark; Minor, Philip; Eloit, Marc; Muth, Erika; Lamamy, Arnaud; Jagorel, Florence; Cheval, Justine; Anscombe, Catherine; Misra, Raju; Wooldridge, David; Gharbia, Saheer; Rose, Graham; Ng, Siemon H.S.; Charlebois, Robert L.; Gisonni-Lex, Lucy; Mallet, Laurent; Dorange, Fabien; Chiu, Charles; Naccache, Samia; Kellam, Paul; van der Hoek, Lia; Cotten, Matt; Mitchell, Christine; Baier, Brian S.; Sun, Wenping; Malicki, Heather D.

    2016-01-01

    Background Unbiased deep sequencing offers the potential for improved adventitious virus screening in vaccines and biotherapeutics. Successful implementation of such assays will require appropriate control materials to confirm assay performance and sensitivity. Methods A common reference material containing 25 target viruses was produced and 16 laboratories were invited to process it using their preferred adventitious virus detection assay. Results Fifteen laboratories returned results, obtained using a wide range of wet-lab and informatics methods. Six of 25 target viruses were detected by all laboratories, with the remaining viruses detected by 4–14 laboratories. Six non-target viruses were detected by three or more laboratories. Conclusion The study demonstrated that a wide range of methods are currently used for adventitious virus detection screening in biological products by deep sequencing and that they can yield significantly different results. This underscores the need for common reference materials to ensure satisfactory assay performance and enable comparisons between laboratories. PMID:26709640

  9. The double-edged sword: How evolution can make or break a live-attenuated virus vaccine

    PubMed Central

    Hanley, Kathryn A.

    2012-01-01

    Even students who reject evolution are often willing to consider cases in which evolutionary biology contributes to, or undermines, biomedical interventions. Moreover the intersection of evolutionary biology and biomedicine is fascinating in its own right. This review offers an overview of the ways in which evolution has impacted the design and deployment of live-attenuated virus vaccines, with subsections that may be useful as lecture material or as the basis for case studies in classes at a variety of levels. Live- attenuated virus vaccines have been modified in ways that restrain their replication in a host, so that infection (vaccination) produces immunity but not disease. Applied evolution, in the form of serial passage in novel host cells, is a “classical” method to generate live-attenuated viruses. However many live-attenuated vaccines exhibit reversion to virulence through back-mutation of attenuating mutations, compensatory mutations elsewhere in the genome, recombination or reassortment, or changes in quasispecies diversity. Additionally the combination of multiple live-attenuated strains may result in competition or facilitation between individual vaccine viruses, resulting in undesirable increases in virulence or decreases in immunogenicity. Genetic engineering informed by evolutionary thinking has led to a number of novel approaches to generate live-attenuated virus vaccines that contain substantial safeguards against reversion to virulence and that ameliorate interference among multiple vaccine strains. Finally, vaccines have the potential to shape the evolution of their wild type counterparts in counter-productive ways; at the extreme vaccine-driven eradication of a virus may create an empty niche that promotes the emergence of new viral pathogens. PMID:22468165

  10. Novel transgenic rice-based vaccines.

    PubMed

    Azegami, Tatsuhiko; Itoh, Hiroshi; Kiyono, Hiroshi; Yuki, Yoshikazu

    2015-04-01

    Oral vaccination can induce both systemic and mucosal antigen-specific immune responses. To control rampant mucosal infectious diseases, the development of new effective oral vaccines is needed. Plant-based vaccines are new candidates for oral vaccines, and have some advantages over the traditional vaccines in cost, safety, and scalability. Rice seeds are attractive for vaccine production because of their stability and resistance to digestion in the stomach. The efficacy of some rice-based vaccines for infectious, autoimmune, and other diseases has been already demonstrated in animal models. We reported the efficacy in mice, safety, and stability of a rice-based cholera toxin B subunit vaccine called MucoRice-CTB. To advance MucoRice-CTB for use in humans, we also examined its efficacy and safety in primates. The potential of transgenic rice production as a new mucosal vaccine delivery system is reviewed from the perspective of future development of effective oral vaccines.

  11. Vaccines against seasonal and pandemic influenza and the implications of changes in substrates for virus production.

    PubMed

    Minor, Philip D

    2010-02-15

    Influenza virus changes constantly, making vaccine production challenging. Changing the growth substrate from eggs to cell culture raises issues at all stages of the process, from surveillance to the assay of vaccines. The pandemic threat-first H5N1, then H1N1-encouraged a review of methods and brought issues into sharp relief.

  12. Vaccines in historic evolution and perspective: a narrative of vaccine discoveries.

    PubMed

    Hilleman, M R

    2000-01-01

    The sciences of vaccinology and immunology were created only two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th- and early 20th-century biomedical sciences. The period from 1930 to 1950 was a transitional era, with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines. Modern vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given at a Meeting of the Institute of Human Virology entitled A Symposium on HIV-AIDS and Cancer Biology, Baltimore, Maryland, on August 30, 1999 and recounts, by invitation, more than 55 years of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references 1 and 2. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.

  13. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

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

  14. Vaccines and Kawasaki disease.

    PubMed

    Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

    2016-01-01

    The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

  15. Anthrax Vaccine

    MedlinePlus

    ... products some military personnel, as determined by the Department of Defense These people should get five doses of vaccine ( ... cdc.gov/agent/anthrax/vaccination/. Contact the U.S Department of Defense (DoD): call 1-877-438-8222 or visit ...

  16. The March Toward Malaria Vaccines.

    PubMed

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-12-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  17. The March Toward Malaria Vaccines

    PubMed Central

    Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

    2016-01-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  18. The march toward malaria vaccines

    PubMed Central

    Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

    2016-01-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  19. The march toward malaria vaccines.

    PubMed

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-11-27

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  20. Dueling biological and social contagions

    PubMed Central

    Fu, Feng; Christakis, Nicholas A.; Fowler, James H.

    2017-01-01

    Numerous models explore how a wide variety of biological and social phenomena spread in social networks. However, these models implicitly assume that the spread of one phenomenon is not affected by the spread of another. Here, we develop a model of “dueling contagions”, with a particular illustration of a situation where one is biological (influenza) and the other is social (flu vaccination). We apply the model to unique time series data collected during the 2009 H1N1 epidemic that includes information about vaccination, flu, and face-to-face social networks. The results show that well-connected individuals are more likely to get vaccinated, as are people who are exposed to friends who get vaccinated or are exposed to friends who get the flu. Our dueling contagion model suggests that other epidemiological models may be dramatically underestimating the R0 of contagions. It also suggests that the rate of vaccination contagion may be even more important than the biological contagion in determining the course of the disease. These results suggest that real world and online platforms that make it easier to see when friends have been vaccinated (personalized vaccination campaigns) and when they get the flu (personalized flu warnings) could have a large impact on reducing the severity of epidemics. They also suggest possible benefits from understanding the coevolution of many kinds of dueling contagions. PMID:28252663

  1. Dueling biological and social contagions

    NASA Astrophysics Data System (ADS)

    Fu, Feng; Christakis, Nicholas A.; Fowler, James H.

    2017-03-01

    Numerous models explore how a wide variety of biological and social phenomena spread in social networks. However, these models implicitly assume that the spread of one phenomenon is not affected by the spread of another. Here, we develop a model of “dueling contagions”, with a particular illustration of a situation where one is biological (influenza) and the other is social (flu vaccination). We apply the model to unique time series data collected during the 2009 H1N1 epidemic that includes information about vaccination, flu, and face-to-face social networks. The results show that well-connected individuals are more likely to get vaccinated, as are people who are exposed to friends who get vaccinated or are exposed to friends who get the flu. Our dueling contagion model suggests that other epidemiological models may be dramatically underestimating the R0 of contagions. It also suggests that the rate of vaccination contagion may be even more important than the biological contagion in determining the course of the disease. These results suggest that real world and online platforms that make it easier to see when friends have been vaccinated (personalized vaccination campaigns) and when they get the flu (personalized flu warnings) could have a large impact on reducing the severity of epidemics. They also suggest possible benefits from understanding the coevolution of many kinds of dueling contagions.

  2. Translation of an experimental oral vaccine formulation into a commercial product.

    PubMed

    Carter, K C; Ferro, V A; Alexander, J; Mullen, A B

    2006-02-01

    An effective experimental vaccine may fail to become a therapeutic reality for a number of scientific, regulatory or commercial reasons. In this review, we share some of our personal experiences as University-based researchers and provide an account of some of the problems that we have encountered during preliminary scale-up and assessment of an oral influenza vaccine formulation. Many of the problems we have faced have been non-scientific and related to identifying project-funding sources, finding suitable contract manufacturing companies that are GMP compliant, and protecting intellectual property generated from the scientific studies. The review is intended as a practical guide that will allow other researchers to adopt effective strategies to permit the translation of an effective experimental formulation to a viable commercial product.

  3. HIV vaccines: new frontiers in vaccine development.

    PubMed

    Duerr, Ann; Wasserheit, Judith N; Corey, Lawrence

    2006-08-15

    A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.

  4. Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy.

    PubMed

    Lund, L; Henmar, H; Würtzen, P A; Lund, G; Hjortskov, N; Larsen, J N

    2007-04-01

    Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid

  5. Tracing and control of raw materials sourcing for vaccine manufacturers.

    PubMed

    Faretra Peysson, Laurence

    2010-05-01

    The control of the raw materials used to manufacture vaccines is mandatory; therefore, a very clear process must be in place to guarantee that raw materials are traced. Those who make products or supplies used in vaccine manufacture (suppliers of culture media, diagnostic tests, etc.) must apply quality systems proving that they adhere to certain standards. ISO certification, Good Manufacturing Practices for production sites and the registration of culture media with a 'Certificate of Suitability' from the European Directorate for the Quality of Medicines and Healthcare are reliable quality systems pertaining to vaccine production. Suppliers must assure that each lot of raw materials used in a product that will be used in vaccine manufacture adheres to the level of safety and traceability required. Incoming materials must be controlled in a single 'Enterprise Resource Planning' system which is used to document important information, such as the assignment of lot number, expiration date, etc. Ingredients for culture media in particular must conform to certain specifications. The specifications that need to be checked vary according to the ingredient, based on the level of risk. The way a raw material is produced is also important, and any aspect relative to cross-contamination, such as the sanitary measures used in producing and storing the raw material must be checked as well. In addition, suppliers can reduce the risk of viral contamination of raw materials by avoiding purchases in countries where a relevant outbreak is currently declared. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  6. The monitoring of antigen levels during inactivated poliovirus vaccine production: evaluation of filtration techniques.

    PubMed

    Moynihan, M; Petersen, I

    1981-01-01

    The use of ELISA to estimate poliovirus antigen concentration has permitted an evaluation of the methodology used in vaccine production and allowed exploration of less wasteful filtration-techniques. The replacement of Seitz-EKS-1B filtration with either Seitz-Supra-EKS or Pall-filtration in the preparation of the vaccine could make a large saving in the total antigen yield, but the results in the safety test excluded their possible use in our process as it stands at the moment.

  7. Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake.

    PubMed

    Malhi, Gurtej; Rumman, Amir; Thanabalan, Reka; Croitoru, Kenneth; Silverberg, Mark S; Hillary Steinhart, A; Nguyen, Geoffrey C

    2015-06-01

    Immunomodulators and biological agents, used to treat inflammatory bowel disease [IBD], are associated with an increased risk of infection, including vaccine-preventable infections. We assessed patient attitudes towards vaccination, knowledge of vaccine recommendations, and uptake of recommended vaccines. Patients attending IBD clinics completed a self-administered, structured, paper-based questionnaire. We collected demographic data, medical and immunisation history, self-reported patient uptake, knowledge, and perceptions of childhood and adult vaccinations. The prevalence of treatment with biologicals, steroids, thiopurines, and methotrexate among the 300 respondents were 37.3%, 16.0%, 16.0%, and 5.7%, respectively. Self-reported vaccine completion was reported by 45.3% of patients. Vaccination uptake rates were 61.3% for influenza, 10.3% for pneumococcus, 61.0% for hepatitis B, 52.0% for hepatitis A, 26.0% for varicella, 20.7% for meningococcus, 5.3% for herpes zoster, and 11.0% for herpes papilloma virus [females only]. Significant predictors of vaccine completion were annual vaccination review by family physician (odds ratio [OR] = 1.82) or gastroenterologist [OR = 1.72], current steroid use [OR = 1.28], and current or prior treatment with biologicals [OR = 1.42]. The majority of patients reported that the primary responsibility to ensure vaccine completion lies with the patient [41.7%] and the family physician [32.3%]. Uncertainty about indications, fears of side effects, and concerns regarding vaccine safety were the most commonly reported reasons for non-uptake [22.0%, 20.7%, and 5.3%, respectively]. Uptake of recommended vaccines among IBD patients is suboptimal. Annual vaccination reviews by both family physician and gastroenterologist may improve vaccine uptake. Interventions targeted at improving vaccination uptake in IBD patients are needed. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All

  8. 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

  9. Pricing of new vaccines.

    PubMed

    Lee, Bruce Y; McGlone, Sarah M

    2010-08-01

    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 ten 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.

  10. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Pseudorabies Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.213 Pseudorabies Vaccine, Killed Virus. Pseudorabies Vaccine, Killed... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  11. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Pseudorabies Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.213 Pseudorabies Vaccine, Killed Virus. Pseudorabies Vaccine, Killed... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  12. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Pseudorabies Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.213 Pseudorabies Vaccine, Killed Virus. Pseudorabies Vaccine, Killed... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  13. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Pseudorabies Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.213 Pseudorabies Vaccine, Killed Virus. Pseudorabies Vaccine, Killed... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  14. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Pseudorabies Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.213 Pseudorabies Vaccine, Killed Virus. Pseudorabies Vaccine, Killed... established as pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All...

  15. Developmental biology of the innate immune response: implications for neonatal and infant vaccine development.

    PubMed

    Philbin, Victoria Jane; Levy, Ofer

    2009-05-01

    Molecular characterization of mechanisms by which human pattern recognition receptors (PRRs) detect danger signals has greatly expanded our understanding of the innate immune system. PRRs include Toll-like receptors, nucleotide oligomerization domain-like receptors, retinoic acid inducible gene-like receptors, and C-type lectin receptors. Characterization of the developmental expression of these systems in the fetus, newborn, and infant is incomplete but has yielded important insights into neonatal susceptibility to infection. Activation of PRRs on antigen-presenting cells enhances costimulatory function, and thus PRR agonists are potential vaccine adjuvants, some of which are already in clinical use. Thus, study of PRRs has also revealed how previously mysterious immunomodulators are able to mediate their actions, including the vaccine adjuvant aluminum hydroxide that activates a cytosolic protein complex known as the Nacht domain leucine-rich repeat and pyrin domain-containing protein 3 inflammasome leading to interleukin-1beta production. Progress in characterizing PRRs is thus informing and expanding the design of improved adjuvants. This review summarizes recent developments in the field of innate immunity emphasizing developmental expression in the fetus, newborn, and infant and its implications for the design of more effective neonatal and infant vaccines.

  16. Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics.

    PubMed

    He, Yongqun

    2012-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning.

  17. Immunization against Genital Herpes with a Vaccine Virus That has Defects in Productive and Latent Infection

    NASA Astrophysics Data System (ADS)

    da Costa, Xavier J.; Jones, Cheryl A.; Knipe, David M.

    1999-06-01

    An effective vaccine for genital herpes has been difficult to achieve because of the limited efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative approach, mutant herpes simplex virus strains that are replication-defective can induce protective immunity. To increase the level of safety and to prove that replication was not needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing two deletion mutations, each of which eliminated viral replication. The double-mutant virus induces protective immunity that can reduce acute viral shedding and latent infection in a mouse genital model, but importantly, the double-mutant virus shows a phenotypic defect in latent infection. This herpes vaccine strain, which is immunogenic but has defects in both productive and latent infection, provides a paradigm for the design of vaccines and vaccine vectors for other sexually transmitted diseases, such as AIDS.

  18. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... bacterial vaccines; (iii) Two samples of Coccidiosis Vaccine; (iv) Eighteen samples of Rabies Vaccine...) Twenty-two single-dose or 14 multiple-dose samples of Rabies Vaccine, Killed Virus; (viii) Sixteen single...

  19. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... bacterial vaccines; (iii) Two samples of Coccidiosis Vaccine; (iv) Eighteen samples of Rabies Vaccine...) Twenty-two single-dose or 14 multiple-dose samples of Rabies Vaccine, Killed Virus; (viii) Sixteen single...

  20. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... bacterial vaccines; (iii) Two samples of Coccidiosis Vaccine; (iv) Eighteen samples of Rabies Vaccine...) Twenty-two single-dose or 14 multiple-dose samples of Rabies Vaccine, Killed Virus; (viii) Sixteen single...

  1. Information Curation among Vaccine Cautious Parents: Web 2.0, Pinterest Thinking, and Pediatric Vaccination Choice.

    PubMed

    Sobo, Elisa J; Huhn, Arianna; Sannwald, Autumn; Thurman, Lori

    2016-01-01

    To learn about pediatric vaccine decision-making, we surveyed and interviewed US parents with at least one child kindergarten age or younger (N = 53). Through an anthropologically informed content analysis, we found that fully vaccinating parents (n = 33) mostly saw vaccination as routine. In contrast, selective and nonvaccinating parents (n = 20) exhibited the type of self-informed engagement that the health care system recommends. Selective vaccinators also expressed multiple, sometimes contradictory positions on vaccination that were keyed to individual children's biologies, child size, environmental hazards, specific diseases, and discrete vaccines. Rather than logical progressions, viewpoints were presented as assembled collections, reflecting contemporary information filtering and curation practices and the prevalence of collectively experienced and constructed digital "hive" narratives. Findings confirm the need for a noncategorical approach to intervention that accommodates the fluid, polyvalent nature of vaccine reasoning and the curatorial view selectively vaccinating parents take toward information while honoring their efforts at engaged healthcare consumption.

  2. A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

    PubMed

    Kaslow, David C

    2004-10-01

    Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

  3. Academe and the Threat of Biological Terrorism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Atlas, Ronald M.; Weller, Richard E.

    1999-04-03

    A legally binding protocol to monitor compliance with Biological and Toxin Weapons Convention (BWC) could have a substantial impact on academia. This is because of the large number of academic sites, and the complexity of activities and business relationships found in academia. Several hundred academic institutions could be required to file declarations, depending upon the specific''triggers'' adopted by the Ad Hoc Group to the BWC. Activities at academic sites that might''trigger'' a requirement for declaration include: biological defense, working with listed agents or toxins, production capacity, biopesticide research, vaccine production, high (BL3) biological containment, and aerobiology. The management structure ofmore » academic institutions will make it difficult for them to scrupulously comply with declaration requirements. A major educational program will be required to ensure academic compliance with any mandatory measures adopted to strengthen the BWC.« less

  4. Disa vaccines for Bluetongue: A novel vaccine approach for insect-borne diseases

    USDA-ARS?s Scientific Manuscript database

    Bluetongue virus (BTV) lacking functional NS3/NS3a protein is named Disabled Infectious Single Animal (DISA) vaccine. The BT DISA vaccine platform is broadly applied by exchange of serotype specific proteins. BT DISA vaccines are produced in standard cell lines in established production facilities, ...

  5. Ten years of PCV2 vaccines and vaccination: Is eradication a possibility?

    PubMed

    Afghah, Zahra; Webb, Brett; Meng, Xiang-Jin; Ramamoorthy, Sheela

    2017-07-01

    More than two decades after its emergence, porcine circovirus type 2 (PCV2) remains an economically important swine pathogen. Commercial vaccines which were first introduced to the U.S in 2006, have been highly effective in reducing clinical signs and improving production. Recent studies have indicated a declining level of PCV2 prevalence and viremia in the field. However, reports on the emergence of new viral variants have also continued to increase. This article reviews topics of current interest in the field of PCV2 vaccines; including the comparative efficacy of the available commercial products, efficacy of current vaccines against new and emerging strains, findings on the differences between immunity in natural infection versus vaccination, limitations of current experimental models for PCV2 vaccine studies, and new developments in novel experimental vaccines. The discussion is framed in the context of attempts for the possible eradication of PCV2 in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Recombinant Alpha, Beta, and Epsilon Toxins of Clostridium perfringens: Production Strategies and Applications as Veterinary Vaccines

    PubMed Central

    Ferreira, Marcos Roberto A.; Moreira, Gustavo Marçal S. G.; da Cunha, Carlos Eduardo P.; Mendonça, Marcelo; Salvarani, Felipe M.; Moreira, Ângela N.; Conceição, Fabricio R.

    2016-01-01

    Clostridium perfringens is a spore-forming, commensal, ubiquitous bacterium that is present in the gastrointestinal tract of healthy humans and animals. This bacterium produces up to 18 toxins. The species is classified into five toxinotypes (A–E) according to the toxins that the bacterium produces: alpha, beta, epsilon, or iota. Each of these toxinotypes is associated with myriad different, frequently fatal, illnesses that affect a range of farm animals and humans. Alpha, beta, and epsilon toxins are the main causes of disease. Vaccinations that generate neutralizing antibodies are the most common prophylactic measures that are currently in use. These vaccines consist of toxoids that are obtained from C. perfringens cultures. Recombinant vaccines offer several advantages over conventional toxoids, especially in terms of the production process. As such, they are steadily gaining ground as a promising vaccination solution. This review discusses the main strategies that are currently used to produce recombinant vaccines containing alpha, beta, and epsilon toxins of C. perfringens, as well as the potential application of these molecules as vaccines for mammalian livestock animals. PMID:27879630

  7. Optimization and scale-up of cell culture and purification processes for production of an adenovirus-vectored tuberculosis vaccine candidate.

    PubMed

    Shen, Chun Fang; Jacob, Danielle; Zhu, Tao; Bernier, Alice; Shao, Zhongqi; Yu, Xuefeng; Patel, Mehul; Lanthier, Stephane; Kamen, Amine

    2016-06-17

    Tuberculosis (TB) is the second leading cause of death by infectious disease worldwide. The only available TB vaccine is the Bacille Calmette-Guerin (BCG). However, parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. AdAg85A, an adenoviral vector expressing the mycobacterial protein Ag85A, is a new tuberculosis vaccine candidate, and has shown promising results in pre-clinical studies and phase I trial. This adenovirus vectored vaccine is produced using HEK 293 cell culture. Here we report on the optimization of cell culture conditions, scale-up of production and purification of the AdAg85A at different scales. Four commercial serum-free media were evaluated under various conditions for supporting the growth of HEK293 cell and production of AdAg85A. A culturing strategy was employed to take advantages of two culture media with respective strengths in supporting the cell growth and virus production, which enabled to maintain virus productivity at higher cell densities and resulted in more than two folds of increases in culture titer. The production of AdAg85A was successfully scaled up and validated at 60L bioreactor under the optimal conditions. The AdAg85A generated from the 3L and 60L bioreactor runs was purified through several purification steps. More than 98% of total cellular proteins was removed, over 60% of viral particles was recovered after the purification process, and purity of AdAg85A was similar to that of the ATCC VR-1516 Ad5 standard. Vaccination of mice with the purified AdAg85A demonstrated a very good level of Ag85A-specific antibody responses. The optimized production and purification conditions were transferred to a GMP facility for manufacturing of AdAg85A for generation of clinical grade material to support clinical trials. Crown Copyright © 2016. Published by Elsevier Ltd. All rights

  8. Synthetic biology advances for pharmaceutical production

    PubMed Central

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

  9. Smallpox vaccines: targets of protective immunity.

    PubMed

    Moss, Bernard

    2011-01-01

    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. Published 2010. This article is a US Government work and is in the public domain in the USA.

  10. Plant-derived vaccines: an approach for affordable vaccines against cervical cancer.

    PubMed

    Waheed, Mohammad Tahir; Gottschamel, Johanna; Hassan, Syed Waqas; Lössl, Andreas Günter

    2012-03-01

    Several types of human papillomavirus (HPV) are causatively associated with cervical cancer, which is the second most common cancer in women worldwide. HPV-16 and 18 are among the high risk types and responsible for HPV infection in more than 70% of the cases. The majority of cervical cancer cases occur in developing countries. Currently available HPV vaccines are expensive and probably unaffordable for most women in low and middle income countries. Therefore, there is a need to develop cost-effective vaccines for these countries. Due to many advantages, plants offer an attractive platform for the development of affordable vaccines. These include low cost of production, scalability, low health risks and the potential ability to be used as unprocessed or partially processed material. Among several techniques, chloroplast transformation is of eminent interest for the production of vaccines because of high yield of foreign protein and lack of transgene transmission through pollen. In this commentary, we focus on the most relevant aspects of plant-derived vaccines that are decisive for the future development of cost-effective HPV vaccines.

  11. A simple method for measuring porcine circovirus 2 whole virion particles and standardizing vaccine formulation.

    PubMed

    Zanotti, Cinzia; Amadori, Massimo

    2015-03-01

    Porcine Circovirus 2 (PCV2) is involved in porcine circovirus-associated disease, that causes great economic losses to the livestock industry worldwide. Vaccination against PCV2 proved to be very effective in reducing disease occurrence and it is currently performed on a large scale. Starting from a previous model concerning Foot-and Mouth Disease Virus antigens, we developed a rapid and simple method to quantify PCV2 whole virion particles in inactivated vaccines. This procedure, based on sucrose gradient analysis and fluorometric evaluation of viral genomic content, allows for a better standardization of the antigen payload in vaccine batches. It also provides a valid indication of virion integrity. Most important, such a method can be applied to whole virion vaccines regardless of the production procedures, thus enabling meaningful comparisons on a common basis. In a future batch consistency approach to PCV2 vaccine manufacture, our procedure represents a valuable tool to improve in-process controls and to guarantee conformity of the final product with passmarks for approval. This might have important repercussions in terms of reduced usage of animals for vaccine batch release, in the framework of the current 3Rs policy. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  12. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological...

  13. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological...

  14. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological...

  15. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological...

  16. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological...

  17. Chemistry, manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers.

    PubMed

    Wahid, Rahnuma; Holt, Renee; Hjorth, Richard; Berlanda Scorza, Francesco

    2016-10-26

    With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  19. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  20. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  1. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  2. 9 CFR 113.302 - Distemper Vaccine-Mink.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Distemper Vaccine-Mink. 113.302... Virus Vaccines § 113.302 Distemper Vaccine—Mink. Distemper Vaccine—Mink shall be prepared from virus... immunogenic shall be used for preparing the production seed virus for vaccine production. All serials of...

  3. 9 CFR 309.11 - Vaccine livestock.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Vaccine livestock. 309.11 Section 309.11 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION ANTE-MORTEM INSPECTION § 309.11 Vaccine livestock. Vaccine livestock with unhealed lesions of...

  4. 9 CFR 309.11 - Vaccine livestock.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Vaccine livestock. 309.11 Section 309.11 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION ANTE-MORTEM INSPECTION § 309.11 Vaccine livestock. Vaccine livestock with unhealed lesions of...

  5. 9 CFR 309.11 - Vaccine livestock.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Vaccine livestock. 309.11 Section 309.11 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION ANTE-MORTEM INSPECTION § 309.11 Vaccine livestock. Vaccine livestock with unhealed lesions of...

  6. 9 CFR 309.11 - Vaccine livestock.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Vaccine livestock. 309.11 Section 309.11 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION ANTE-MORTEM INSPECTION § 309.11 Vaccine livestock. Vaccine livestock with unhealed lesions of...

  7. 9 CFR 309.11 - Vaccine livestock.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Vaccine livestock. 309.11 Section 309.11 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... CERTIFICATION ANTE-MORTEM INSPECTION § 309.11 Vaccine livestock. Vaccine livestock with unhealed lesions of...

  8. Two Case Studies in the Scientific Method: Antisense Experiments and HIV Vaccination Studies.

    ERIC Educational Resources Information Center

    Guilfoile, Patrick

    1999-01-01

    Presents two recent cases that can be used in the classroom to illustrate the application of scientific methods in biological research: (1) the use of a complementary RNA or DNA molecule to block the production or translation of an mRNA molecule; and (2) the development of HIV trial vaccines. Contains 20 references. (WRM)

  9. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Packaging biological products. 112.6 Section 112.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... if seal is broken.” (d) Diluent for the following products need not be packaged with the final...

  10. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Packaging biological products. 112.6 Section 112.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... if seal is broken.” (d) Diluent for the following products need not be packaged with the final...

  11. Immunologic considerations for generating memory CD8 T cells through vaccination.

    PubMed

    Butler, Noah S; Nolz, Jeffrey C; Harty, John T

    2011-07-01

    Following infection or vaccination, naïve CD8 T cells that receive the appropriate integration of antigenic, co-stimulatory and inflammatory signals undergo a programmed series of biological changes that ultimately results in the generation of memory cells. Memory CD8 T cells, in contrast to naïve cells, more effectively limit or prevent pathogen re-infection because of both qualitative and quantitative changes that occur following their induction. Unlike vaccination strategies aimed at generating antibody production, the ability to generate protective memory CD8 T cells has proven more complicated and problematic. However, recent experimental results have revealed important principles regarding the molecular and genetic basis for memory CD8 T cell formation, as well as identified ways to manipulate their development through vaccination, resulting in potential new avenues to enhance protective immunity. © 2011 Blackwell Publishing Ltd.

  12. Ensuring the optimal safety of licensed vaccines: a perspective of the vaccine research, development, and manufacturing companies.

    PubMed

    Kanesa-thasan, Niranjan; Shaw, Alan; Stoddard, Jeffrey J; Vernon, Thomas M

    2011-05-01

    Vaccine safety is increasingly a focus for the general public, health care providers, and vaccine manufacturers, because the efficacy of licensed vaccines is accepted as a given. Commitment to ensuring safety of all vaccines, including childhood vaccines, is addressed by the federal government, academia, and industry. Safety activities conducted by the vaccine research, development, and manufacturing companies occur at all stages of product development, from selection and formulation of candidate vaccines through postlicensure studies and surveillance of adverse-event reports. The contributions of multiple interacting functional groups are required to execute these tasks through the life cycle of a product. We describe here the safeguards used by vaccine manufacturers, including specific examples drawn from recent experience, and highlight some of the current challenges. Vaccine-risk communication becomes a critical area for partnership of vaccine companies with government, professional associations, and nonprofit advocacy groups to provide information on both benefits and risks of vaccines. The crucial role of the vaccine companies in ensuring the optimal vaccine-safety profile, often overlooked, will continue to grow with this dynamic arena.

  13. Safe use of vaccines and vaccine compliance with food safety requirements.

    PubMed

    Grein, K; Papadopoulos, O; Tollis, M

    2007-08-01

    Advanced technologies and regulatory regimes have contributed to the availability of veterinary vaccines that have high quality and favourable safety profiles in terms of potential risks posed to the target animals, the persons who come into contact with the vaccine, the consumers of food derived from vaccinated animals and the environment. The authorisation process requires that a range of safety studies are provided to evaluate the products. The design and production of vaccines, and their safe use, are primarily assessed by using data gathered from extensive pre-marketing studies performed on target animals and specific quality tests. The current post-marketing safeguards include good manufacturing practices, batch safety testing, inspections and pharmacovigilance. In addition to hazard identification, a full benefit/risk evaluation needs to be undertaken. The outcome of that evaluation will determine options for risk management and affect regulatory decisions on the safety of the vaccine; options might, for example, include special warnings on package inserts and labels.

  14. 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

    2014-10-07

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Traditional and New Influenza Vaccines

    PubMed Central

    Wong, Sook-San

    2013-01-01

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

  16. Schistosomiasis vaccine development: approaches and prospects.

    PubMed

    Bergquist, N R

    1995-01-01

    Mounting evidence for acquired immunity to schistosomiasis in humans supports the case for immunological intervention. On the other hand, rapid reinfection poses a threat to younger age groups due to the slow maturation of natural resistance. However, rational approaches, based on advances in immunology and molecular biology, have substantially increased the odds of producing an effective vaccine. Since the parasite cannot replicate in the human host and serious morbidity generally occurs only after a relatively long period of heavy worm burden, complete protection against infection is not essential. The chances of success would increase if more than one of the various host/parasite interphases were targeted, for example reducing morbidity through decreased worm loads as well as through suppression of egg production. Several promising schistosome antigens have now reached an advanced phase of development and are currently undergoing independent confirmatory testing according to a standardized protocol. A few molecules are being contemplated for scaled-up production but, so far, only one has reached the stage of industrial manufacture and safety testing. Since schistosomiasis cannot realistically be controlled by a single approach, vaccination is envisaged to be implemented in conjunction with other means of control, notably chemotherapy.

  17. Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production.

    PubMed

    Tapia, Felipe; Vázquez-Ramírez, Daniel; Genzel, Yvonne; Reichl, Udo

    2016-03-01

    With an increasing demand for efficacious, safe, and affordable vaccines for human and animal use, process intensification in cell culture-based viral vaccine production demands advanced process strategies to overcome the limitations of conventional batch cultivations. However, the use of fed-batch, perfusion, or continuous modes to drive processes at high cell density (HCD) and overextended operating times has so far been little explored in large-scale viral vaccine manufacturing. Also, possible reductions in cell-specific virus yields for HCD cultivations have been reported frequently. Taking into account that vaccine production is one of the most heavily regulated industries in the pharmaceutical sector with tough margins to meet, it is understandable that process intensification is being considered by both academia and industry as a next step toward more efficient viral vaccine production processes only recently. Compared to conventional batch processes, fed-batch and perfusion strategies could result in ten to a hundred times higher product yields. Both cultivation strategies can be implemented to achieve cell concentrations exceeding 10(7) cells/mL or even 10(8) cells/mL, while keeping low levels of metabolites that potentially inhibit cell growth and virus replication. The trend towards HCD processes is supported by development of GMP-compliant cultivation platforms, i.e., acoustic settlers, hollow fiber bioreactors, and hollow fiber-based perfusion systems including tangential flow filtration (TFF) or alternating tangential flow (ATF) technologies. In this review, these process modes are discussed in detail and compared with conventional batch processes based on productivity indicators such as space-time yield, cell concentration, and product titers. In addition, options for the production of viral vaccines in continuous multi-stage bioreactors such as two- and three-stage systems are addressed. While such systems have shown similar virus titers compared to

  18. Lessons learned: role of influenza vaccine production, distribution, supply, and demand--what it means for the provider.

    PubMed

    Orenstein, Walter A; Schaffner, William

    2008-07-01

    The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) has been increasing the size of the population for whom influenza vaccine is recommended to reduce the substantial and persistent annual health burden of influenza. Realization of current and future public health influenza immunization goals requires assuring vaccine supply will be adequate to meet demand. This has posed distinct challenges for the many stakeholders in the influenza vaccine program--government agencies, federal, state, and local policymakers, vaccine manufacturers and distributors, and the medical community--each of whom must make critical decisions in a constantly shifting environment. Factors such as the yearly changes in influenza virus strains, the complicated vaccine production and distribution process, revisions in vaccination recommendations, and changing demographics can all affect the delicate balance between supply and demand. While vaccine shortages and delays have been well-publicized concerns in the recent past, there has been a marked increase in supply in the past several years, with substantial growth in supply expected in the future. The primary issue today is to strengthen the demand for the influenza vaccine, which would in turn help ensure the continued availability of the vaccine to reduce disease burden. A number of strategies are discussed, including increased efforts to publicize and fully implement current CDC recommendations and to offer influenza vaccine beyond the typical vaccination season of October and November, because in the great majority of years, vaccination into January and beyond will still provide health benefits.

  19. Role of vaccination in economic growth.

    PubMed

    Quilici, Sibilia; Smith, Richard; Signorelli, Carlo

    2015-01-01

    The health of a population is important from a public health and economic perspective as healthy individuals contribute to economic growth. Vaccination has the potential to contribute substantially to improving population health and thereby economic growth. Childhood vaccination programmes in Europe can offer protection against 15 important infectious diseases, thus preventing child fatalities and any serious temporary and permanent sequelae that can occur. Healthy children are more able to participate in education, thus preparing them to become healthy and productive adults. Vaccination programmes can also prevent infectious diseases in adolescents, thus allowing them to continue their development towards a healthy adulthood. Protecting adults against infectious diseases ensures that they can fully contribute to productivity and economic development by avoiding sick leave and lower productivity. Vaccination in older adults will contribute to the promotion of healthy ageing, enabling them to assist their familiy with, for instance, childcare, and also help them avoid functional decline and the related impacts on health and welfare expenditure. Effective vaccination programmes for all ages in Europe will thus contribute to the European Union's 2020 health and economic strategies. Indeed, beyond their impact on healthcare resources and productivity, reductions in mortality and morbidity also contribute to increased consumption and gross domestic product. Therefore, assessment of the value of vaccines and vaccination needs to consider not just the direct impact on health and healthcare but also the wider impact on economic growth, which requires a macroeconomic analysis of vaccination programmes.

  20. Role of vaccination in economic growth

    PubMed Central

    Quilici, Sibilia; Smith, Richard; Signorelli, Carlo

    2015-01-01

    The health of a population is important from a public health and economic perspective as healthy individuals contribute to economic growth. Vaccination has the potential to contribute substantially to improving population health and thereby economic growth. Childhood vaccination programmes in Europe can offer protection against 15 important infectious diseases, thus preventing child fatalities and any serious temporary and permanent sequelae that can occur. Healthy children are more able to participate in education, thus preparing them to become healthy and productive adults. Vaccination programmes can also prevent infectious diseases in adolescents, thus allowing them to continue their development towards a healthy adulthood. Protecting adults against infectious diseases ensures that they can fully contribute to productivity and economic development by avoiding sick leave and lower productivity. Vaccination in older adults will contribute to the promotion of healthy ageing, enabling them to assist their familiy with, for instance, childcare, and also help them avoid functional decline and the related impacts on health and welfare expenditure. Effective vaccination programmes for all ages in Europe will thus contribute to the European Union's 2020 health and economic strategies. Indeed, beyond their impact on healthcare resources and productivity, reductions in mortality and morbidity also contribute to increased consumption and gross domestic product. Therefore, assessment of the value of vaccines and vaccination needs to consider not just the direct impact on health and healthcare but also the wider impact on economic growth, which requires a macroeconomic analysis of vaccination programmes. PMID:27123174

  1. Liposomal adjuvants for human vaccines.

    PubMed

    Alving, Carl R; Beck, Zoltan; Matyas, Gary R; Rao, Mangala

    2016-06-01

    Liposomes are well-known as drug carriers, and are now critical components of two of six types of adjuvants present in licensed vaccines. The liposomal vaccine adjuvant field has long been dynamic and innovative, and research in this area is further examined as new commercial products appear in parallel with new vaccines. In an arena where successful products exist the potential for new types of vaccines with liposomal adjuvants, and alternative liposomal adjuvants that could emerge for new types of vaccines, are discussed. Major areas include: virosomes, constructed from phospholipids and proteins from influenza virus particles; liposomes containing natural and synthetic neutral or anionic phospholipids, cholesterol, natural or synthetic monophosphoryl lipid A, and QS21 saponin; non-phospholipid cationic liposomes; and combinations and mixtures of liposomes and immunostimulating ingredients as adjuvants for experimental vaccines. Liposomes containing monophosphoryl lipid A and QS21 have considerable momentum that will result soon in emergence of prophylactic vaccines to malaria and shingles, and possible novel cancer vaccines. The licensed virosome vaccines to influenza and hepatitis A will be replaced with virosome vaccines to other infectious diseases. Alternative liposomal formulations are likely to emerge for difficult diseases such as tuberculosis or HIV-1 infection.

  2. Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

    PubMed Central

    He, Yongqun

    2011-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning. PMID:22919594

  3. Bovine adenovirus-3 as a vaccine delivery vehicle.

    PubMed

    Ayalew, Lisanework E; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K

    2015-01-15

    The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Epidemiological determinants of successful vaccine development.

    PubMed

    Nishiura, Hiroshi; Mizumoto, Kenji

    2013-01-01

    Epidemiological determinants of successful vaccine development were explored using measurable biological variables including antigenic stability and requirement of T-cell immunity. Employing a logistic regression model, we demonstrate that a high affinity with blood and immune cells and pathogen interactions (e.g. interference) would be the risk factors of failure for vaccine development.

  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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.

    PubMed

    Germain, Ronald N

    2017-10-16

    A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system ( omics ), (2) statistical analysis of large data sets ( bioinformatics ), and (3) the capacity of quantitative computational methods to translate these individual components and connections into models of emergent behavior ( systems biology ), we will be able to better understand how the overall immune system functions and to determine with greater precision how to manipulate it to produce desired protective responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  7. Biologic Activity of Autologous, Granulocyte-Macrophage Colony Stimulating Factor Secreting Alveolar Soft Parts Sarcoma and Clear Cell Sarcoma Vaccines

    PubMed Central

    Goldberg, John; Fisher, David E.; Demetri, George D.; Neuberg, Donna; Allsop, Stephen A.; Fonseca, Catia; Nakazaki, Yukoh; Nemer, David; Raut, Chandrajit P.; George, Suzanne; Morgan, Jeffrey A.; Wagner, Andrew J.; Freeman, Gordon J.; Ritz, Jerome; Lezcano, Cecilia; Mihm, Martin; Canning, Christine; Hodi, F. Stephen; Dranoff, Glenn

    2015-01-01

    Purpose Alveolar soft parts sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). Experimental Design Metastatic tumors from ASPS and CCS patients were resected, processed to single cell suspensions, transduced with a replication defective adenoviral vector encoding GM-CSF, and irradiated. Immunizations were administered subcutaneously and intradermally weekly times three and then every other week. Results Vaccines were successfully manufactured for 11 of the 12 enrolled patients. Eleven subjects received from 3 to 13 immunizations. Toxicities were restricted to grade 1–2 skin reactions at inoculation sites. Vaccination elicited local dendritic cell infiltrates and stimulated T cell mediated delayed type-hypersensitivity reactions to irradiated, autologous tumor cells. Antibody responses to tissue-type plasminogen activator (tTPA) and angiopoietins-1/2 were detected. Tumor biopsies showed programmed death-1 (PD-1) positive CD8+ T cells in association with PD ligand-1 (PD-L1) expressing sarcoma cells. No tumor regressions were observed. Conclusions Vaccination with irradiated, GM-CSF secreting autologous sarcoma cell vaccines is feasible, safe, and biologically active. Concurrent targeting of angiogenic cytokines and antagonism of the PD-1 negative regulatory pathway might intensify immune-mediated tumor destruction. PMID:25805798

  8. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials of...

  9. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials of...

  10. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... for vaccine production. All serials shall be prepared from the first through the fifth passage from...

  11. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... for vaccine production. All serials shall be prepared from the first through the fifth passage from...

  12. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials of...

  13. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... for vaccine production. All serials shall be prepared from the first through the fifth passage from...

  14. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials of...

  15. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... for vaccine production. All serials shall be prepared from the first through the fifth passage from...

  16. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... for vaccine production. All serials shall be prepared from the first through the fifth passage from...

  17. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... this section? (1) You, the manufacturer who holds the biological product license and who had control... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Reporting of biological product deviations by... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Establishment Standards...

  18. Now That You Want to Take Your HIV/AIDS Vaccine/Biological Product Research Concept into the Clinic: What are “cGMP”?

    PubMed Central

    Sheets, Rebecca L.; Rangavajhula, Vijaya; Pullen, Jeffrey K.; Butler, Chris; Mehra, Vijay; Shapiro, Stuart

    2015-01-01

    The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of “cGMP” and know that they are supposed to make a “GMP product” to take into the clinic, but often they are not very familiar with what “cGMP” means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked “can’t we use the material we made in the lab in the clinic?” or “aren’t Phase 1 studies exempt from cGMP?” Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. PMID:25698494

  19. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial.

    PubMed

    Howard, Leigh M; Hoek, Kristen L; Goll, Johannes B; Samir, Parimal; Galassie, Allison; Allos, Tara M; Niu, Xinnan; Gordy, Laura E; Creech, C Buddy; Prasad, Nripesh; Jensen, Travis L; Hill, Heather; Levy, Shawn E; Joyce, Sebastian; Link, Andrew J; Edwards, Kathryn M

    2017-01-01

    Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. ClinicalTrials.gov NCT01573312.

  20. Suitability of differently formulated dry powder Newcastle disease vaccines for mass vaccination of poultry.

    PubMed

    Huyge, Katrien; Van Reeth, Kristien; De Beer, Thomas; Landman, Wil J M; van Eck, Jo H H; Remon, Jean Paul; Vervaet, Chris

    2012-04-01

    Dry powders containing a live-attenuated Newcastle disease vaccine (LZ58 strain) and intended for mass vaccination of poultry were prepared by spray drying using mannitol in combination with trehalose or inositol, polyvinylpyrrolidone (PVP) and/or bovine serum albumin (BSA) as stabilizers. These powders were evaluated for vaccine stabilizing capacity during production and storage (at 6 °C and 25 °C), moisture content, hygroscopicity and dry powder dispersibility. A mixture design, varying the ratio of mannitol, inositol and BSA, was used to select the stabilizer combination which resulted in the desired powder properties (i.e. good vaccine stability during production and storage, low moisture content and hygroscopicity and good dry dispersibility). Inositol-containing powders had the same vaccine stabilizing capacity as trehalose powders, but were less hygroscopic. Incorporation of BSA enhanced the vaccine stability in the powders compared to PVP-containing formulations. However, increasing the BSA concentration increased the hygroscopicity and reduced the dry dispersibility of the powder. No valid mathematical model could be calculated for vaccine stability during production or storage, but the individual experiments indicated that a formulation combining mannitol, inositol and BSA in a ratio of 73.3:13.3:13.3 (wt/wt) resulted in the lowest vaccine titre loss during production (1.6-2.0 log(10) 50% egg infectious dose (EID(50)) and storage at 6 °C (max. 0.8 log(10) EID(50) after 6 months) in combination with a low moisture content (1.1-1.4%), low hygroscopicity (1.9-2.1% water uptake at 60% relative humidity) and good dry dispersibility properties. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Mechanistic insights into influenza vaccine-associated narcolepsy.

    PubMed

    Ahmed, S Sohail; Steinman, Lawrence

    2016-12-01

    We previously reported an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera obtained from narcoleptic patients who received the European AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross-reacted with a particular fragment of influenza nucleoprotein (NP) - one of the proteins naturally contained in the virus used to make seasonal influenza vaccine and pandemic influenza vaccines. The purpose of this commentary is to provide additional insights and interpretations of the findings and share additional data not presented in the original paper to help the reader appreciate the key messages of that publication. First, a brief background to narcolepsy and vaccine-induced narcolepsy will be provided. Then, additional insights and clarification will be provided on the following topics: 1) the critical difference identified in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for the discordant association of narcolepsy between the AS03-adjuvanted pandemic vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish control subjects, 4) the approach used for the detection of HCRTr2 antibodies in vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism involving HCRTr2 modulation in vaccine-associated narcolepsy.

  2. Recent advances towards tuberculosis control: vaccines and biomarkers

    PubMed Central

    Weiner, J; Kaufmann, S H E

    2014-01-01

    Weiner 3rd J, Kaufmann SHE (Max Planck Institute for Infection Biology, Berlin, Germany). Recent advances towards tuberculosis control: vaccines and biomarkers. (Review). J Intern Med 2014; 275: 467–480. Of all infectious diseases, tuberculosis (TB) remains one of the most important causes of morbidity and mortality. Recent advances in understanding the biology of Mycobacterium tuberculosis (Mtb) infection and the immune response of the infected host have led to the development of several new vaccines, a number of which are already undergoing clinical trials. These include pre-exposure prime vaccines, which could replace bacille Calmette–Guérin (BCG), and pre-exposure booster vaccines given in addition to BCG. Infants are the target population of these two types of vaccines. In addition, several postexposure vaccines given during adolescence or adult life, in addition to BCG as a priming vaccine during infancy, are undergoing clinical testing. Therapeutic vaccines are currently being assessed for their potential to cure active TB as an adjunct to chemotherapy. BCG replacement vaccines are viable recombinant BCG or double-deletion mutants of Mtb. All booster vaccines are composed of one or several antigens, either expressed by viral vectors or formulated with adjuvants. Therapeutic vaccines are killed mycobacterial preparations. Finally, multivariate biomarkers and biosignatures are being generated from high-throughput data with the aim of providing better diagnostic tools to specifically determine TB progression. Here, we provide a technical overview of these recent developments as well of the relevant computational approaches and highlight the obstacles that still need to be overcome. PMID:24635488

  3. Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges

    PubMed Central

    Nan, Yuchen; Wu, Chunyan; Zhao, Qin; Sun, Yani; Zhang, Yan-Jin; Zhou, En-Min

    2018-01-01

    Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection. PMID:29520257

  4. Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges.

    PubMed

    Nan, Yuchen; Wu, Chunyan; Zhao, Qin; Sun, Yani; Zhang, Yan-Jin; Zhou, En-Min

    2018-01-01

    Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection.

  5. Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller.

    PubMed

    Soons, Zita I T A; van den IJssel, Jan; van der Pol, Leo A; van Straten, Gerrit; van Boxtel, Anton J B

    2009-04-01

    This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer. These gas phase dynamics are modelled using knowledge of the system in order to reconstruct oxygen consumption. The second aspect is to evaluate performance of the monitoring and control system with the required modifications of the oxygen consumption calculation on pilot-scale. In pilot-scale fed-batch cultivation good monitoring and control performance is obtained enabling a doubled concentration of bulk vaccine compared to standard batch production.

  6. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reporting of biological product deviations by... § 600.14 Reporting of biological product deviations by licensed manufacturers. (a) Who must report under...) For biological products regulated by the Center for Biologics Evaluation and Research (CBER), send the...

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

    PubMed

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

    2015-02-01

    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. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  8. Valuing vaccination.

    PubMed

    Bärnighausen, Till; Bloom, David E; Cafiero-Fonseca, Elizabeth T; O'Brien, Jennifer Carroll

    2014-08-26

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.

  9. High stability of yellow fever 17D-204 vaccine: a 12-year restrospective analysis of large-scale production.

    PubMed

    Barban, V; Girerd, Y; Aguirre, M; Gulia, S; Pétiard, F; Riou, P; Barrere, B; Lang, J

    2007-04-12

    We have retrospectively analyzed 12 bulk lots of yellow fever vaccine Stamaril, produced between 1990 and 2002 and prepared from the same seed lot that has been in continuous use since 1990. All vaccine batches displayed identical genome sequence. Only four nucleotide substitutions were observed, compared to previously published sequence, with no incidence at amino-acid level. Fine analysis of viral plaque size distribution was used as an additional marker for genetic stability and demonstrated a remarkable homogeneity of the viral population. The total virus load, measured by qRT-PCR, was also homogeneous pointing out reproducibility of the vaccine production process. Mice inoculated intracerebrally with the different bulks exhibited a similar average survival time, and ratio between in vitro potency and mouse LD(50) titers remained constant from batch-to-batch. Taken together, these data demonstrate the genetic stability of the strain at mass production level over a period of 12 years and reinforce the generally admitted idea of the safety of YF17D-based vaccines.

  10. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine.

    PubMed

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-04-01

    Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.

  11. Vaccines Against Malaria

    PubMed Central

    Ouattara, Amed; Laurens, Matthew B.

    2015-01-01

    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

  12. 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

  13. Cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human chagas disease.

    PubMed

    Seid, Christopher A; Jones, Kathryn M; Pollet, Jeroen; Keegan, Brian; Hudspeth, Elissa; Hammond, Molly; Wei, Junfei; McAtee, C Patrick; Versteeg, Leroy; Gutierrez, Amanda; Liu, Zhuyun; Zhan, Bin; Respress, Jonathan L; Strych, Ulrich; Bottazzi, Maria Elena; Hotez, Peter J

    2017-03-04

    A therapeutic vaccine for human Chagas disease is under development by the Sabin Vaccine Institute Product Development Partnership. The aim of the vaccine is to significantly reduce the parasite burden of Trypanosoma cruzi in humans, either as a standalone product or in combination with conventional chemotherapy. Vaccination of mice with Tc24 formulated with monophosphoryl-lipid A (MPLA) adjuvant results in a Th1 skewed immune response with elevated IgG2a and IFNγ levels and a statistically significant decrease in parasitemia following T. cruzi challenge. Tc24 was therefore selected for scale-up and further evaluation. During scale up and downstream process development, significant protein aggregation was observed due to intermolecular disulfide bond formation. To prevent protein aggregation, cysteine codons were replaced with serine codons which resulted in the production of a non-aggregated and soluble recombinant protein, Tc24-C4. No changes to the secondary structure of the modified molecule were detected by circular dichroism. Immunization of mice with wild-type Tc24 or Tc24-C4, formulated with E6020 (TLR4 agonist analog to MPLA) emulsified in a squalene-oil-in-water emulsion, resulted in IgG2a and antigen specific IFNγ production levels from splenocytes that were not significantly different, indicating that eliminating putative intermolecular disulfide bonds had no significant impact on the immunogenicity of the molecule. In addition, vaccination with either formulated wild type Tc24 or Tc24-C4 antigen also significantly increased survival and reduced cardiac parasite burden in mice. Investigations are now underway to examine the efficacy of Tc24-C4 formulated with other adjuvants to reduce parasite burden and increase survival in pre-clinical studies.

  14. Cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human chagas disease

    PubMed Central

    Jones, Kathryn M.; Keegan, Brian; Hudspeth, Elissa; Hammond, Molly; Wei, Junfei; McAtee, C. Patrick; Versteeg, Leroy; Gutierrez, Amanda; Liu, Zhuyun; Zhan, Bin; Respress, Jonathan L.; Strych, Ulrich; Bottazzi, Maria Elena; Hotez, Peter J.

    2017-01-01

    ABSTRACT A therapeutic vaccine for human Chagas disease is under development by the Sabin Vaccine Institute Product Development Partnership. The aim of the vaccine is to significantly reduce the parasite burden of Trypanosoma cruzi in humans, either as a standalone product or in combination with conventional chemotherapy. Vaccination of mice with Tc24 formulated with monophosphoryl-lipid A (MPLA) adjuvant results in a Th1 skewed immune response with elevated IgG2a and IFNγ levels and a statistically significant decrease in parasitemia following T. cruzi challenge. Tc24 was therefore selected for scale-up and further evaluation. During scale up and downstream process development, significant protein aggregation was observed due to intermolecular disulfide bond formation. To prevent protein aggregation, cysteine codons were replaced with serine codons which resulted in the production of a non-aggregated and soluble recombinant protein, Tc24-C4. No changes to the secondary structure of the modified molecule were detected by circular dichroism. Immunization of mice with wild-type Tc24 or Tc24-C4, formulated with E6020 (TLR4 agonist analog to MPLA) emulsified in a squalene-oil-in-water emulsion, resulted in IgG2a and antigen specific IFNγ production levels from splenocytes that were not significantly different, indicating that eliminating putative intermolecular disulfide bonds had no significant impact on the immunogenicity of the molecule. In addition, vaccination with either formulated wild type Tc24 or Tc24-C4 antigen also significantly increased survival and reduced cardiac parasite burden in mice. Investigations are now underway to examine the efficacy of Tc24-C4 formulated with other adjuvants to reduce parasite burden and increase survival in pre-clinical studies. PMID:27737611

  15. 77 FR 22282 - Draft Guidelines on Biologics Quality Monitoring: Testing for the Detection of Mycoplasma...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ...] Draft Guidelines on Biologics Quality Monitoring: Testing for the Detection of Mycoplasma Contamination... Detection of Mycoplasma Contamination.'' This draft guideline identifies stages of manufacture where... contamination. Because the guidelines apply to final product and master seed/cell testing in veterinary vaccines...

  16. Louis Pasteur, from crystals of life to vaccination.

    PubMed

    Berche, P

    2012-10-01

    Louis Pasteur (1822-1895) is an exceptional scientist who opened a new era in medicine and biology. Starting from studies on crystals of by-products of wine fermentation, he first defined a distinct chemistry between dead and living matters. He then showed the role of living microbes in the fermentation and putrefaction processes. This brought him to challenge the two-millennium-old theory of spontaneous generation, using remarkably well-designed experiments. His observations on epidemics in silkworms allowed him to demonstrate the role of specific germs in infectious diseases. His discovery of the vaccine against fowl cholera can be considered as the birth of immunology. Finally, he became universally recognized through his famous vaccinations against anthrax and rabies. © 2012 The Author. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  17. Vaccines against malaria-still a long way to go.

    PubMed

    Matuschewski, Kai

    2017-08-01

    Several species of Plasmodium cause a broad spectrum of human disease that range from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure. In malaria-endemic countries, continuous exposure to Plasmodium sporozoite inoculations and subsequent blood infections elicit only partial and short-lived immunity, which gradually develops over many years of parasite exposure and multiple clinical episodes. The ambitious goal of malaria vaccinology over the past 70 years has been to develop an immunization strategy that mounts protection superior to naturally acquired immunity. Herein, three principal concepts in evidence-based malaria vaccine development are compared. Feasible leads are typically stand-alone subunit vaccine approaches that block Plasmodium parasite life cycle progression or parasite/host interactions, and they constitute the majority of candidates in preclinical research and early clinical testing. Integrated approaches incorporate malaria antigen(s) into licensed or emerging pediatric vaccine formulations. This strategy can complement the malaria control portfolio even if the antimalarial component is only partially effective and has led to the development of the only candidate vaccine to date, namely RTS,S-AS01. Experimental whole parasite vaccine approaches have been repeatedly shown to elicit sterile and lasting protection against identical parasite strains, but mass production, proof of broad protection against different parasite strains, and routes of vaccine delivery remain significant translational road blocks. Global access to an effective and affordable malaria vaccine will critically depend on innovative translational research that builds on a better molecular understanding of Plasmodium biology and host immunity. © 2017 Federation of European Biochemical Societies.

  18. Yellow fever vector live-virus vaccines: West Nile virus vaccine development.

    PubMed

    Arroyo, J; Miller, C A; Catalan, J; Monath, T P

    2001-08-01

    By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA virus vaccine, has been manipulated to induce a protective immune response against viruses of the same family (e.g. Japanese encephalitis and dengue viruses). Triggered by the emergence of West Nile virus infections in the New World afflicting humans, horses and birds, the success of this recombinant technology has prompted the rapid development of a live-virus attenuated candidate vaccine against West Nile virus.

  19. Emerging Vaccine Therapy Approaches for Prostate Cancer

    PubMed Central

    Sonpavde, Guru; Slawin, Kevin M; Spencer, David M; Levitt, Jonathan M

    2010-01-01

    Prostate cancer vaccines attempt to induce clinically relevant, cancer-specific systemic immune responses in patients with prostate cancer and represent a new class of targeted, nontoxic therapies. With a growing array of vaccine technologies in preclinical or clinical development, autologous antigen-presenting cell vaccines loaded with the antigen, prostate acid phosphatase, and poxvirus vaccines targeting prostate-specific antigen have recently demonstrated a significant survival benefit in randomized trials of patients with metastatic castration-resistant prostate cancer, whereas others have failed to demonstrate any benefit. The combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue to build on these early successes. PMID:20428291

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

    PubMed

    Ortiz de Lejarazu, Raúl; Tamames, Sonia

    2015-01-01

    Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  1. Robustness testing in pharmaceutical freeze-drying: inter-relation of process conditions and product quality attributes studied for a vaccine formulation.

    PubMed

    Schneid, Stefan C; Stärtzel, Peter M; Lettner, Patrick; Gieseler, Henning

    2011-01-01

    The recent US Food and Drug Administration (FDA) legislation has introduced the evaluation of the Design Space of critical process parameters in manufacturing processes. In freeze-drying, a "formulation" is expected to be robust when minor deviations of the product temperature do not negatively affect the final product quality attributes. To evaluate "formulation" robustness by investigating the effect of elevated product temperature on product quality using a bacterial vaccine solution. The vaccine solution was characterized by freeze-dry microscopy to determine the critical formulation temperature. A conservative cycle was developed using the SMART™ mode of a Lyostar II freeze dryer. Product temperature was elevated to imitate intermediate and aggressive cycle conditions. The final product was analyzed using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), Karl Fischer, and modulated differential scanning calorimetry (MDSC), and the life cell count (LCC) during accelerated stability testing. The cakes processed at intermediate and aggressive conditions displayed larger pores with microcollapse of walls and stronger loss in LCC than the conservatively processed product, especially during stability testing. For all process conditions, a loss of the majority of cells was observed during storage. For freeze-drying of life bacterial vaccine solutions, the product temperature profile during primary drying appeared to be inter-related to product quality attributes.

  2. New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication

    PubMed Central

    Knowlson, Sarah; Burlison, John; Giles, Elaine; Fox, Helen; Macadam, Andrew J.; Minor, Philip D.

    2015-01-01

    Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization’s Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5’ non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so. PMID:26720150

  3. New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication.

    PubMed

    Knowlson, Sarah; Burlison, John; Giles, Elaine; Fox, Helen; Macadam, Andrew J; Minor, Philip D

    2015-12-01

    Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.

  4. [From new vaccine to new target: revisiting influenza vaccination].

    PubMed

    Gérard, M

    2011-09-01

    Annual vaccination is since many years the corner stone of Influenza control strategy. Because conventional vaccine are needle-based, are less immunogenic in old people and induce only systemic IgG production, intranasal and intradermal vaccines that are recently or will be soon available in Belgium will offer distinct advantages. Intradermal vaccination is on the Belgian market since 2010. A stronger immune response that allows an antigen sparing strategy is elicited because antigens are delivered near the dermal dendritic cells. Local side effects are more pronounced than after intramuscular injection. The needle-free intranasal vaccine that has been approved for use in people less than 18 years old by the EMEA in October 2010 induces also a mucosal IgA response. Improved clinical results than with intramuscular vaccine has been documented in several studies in children. Several conditions are contraindication to nasal vaccination because of patterns of side effects and because the vaccine is an live-attenuated vaccine. Pregnant women has become a top priority for Influenza vaccination in the recommendations of the High Council of Health in Belgium since the 2009 H1N1 pandemic. Several studies has since then documented the increased risk for Influenza-related morbidity in pregnant women especially during the third trimester and independently of the presence of other comorbidities. Reduced incidence of documented Influenza and of Influenza-related hospitalizations are observed in the new born of vaccinated women until 6 months of age. Availability of new vaccines for Influenza and better knowledge of the benefit of vaccination in target populations are important tools to optimize vaccine coverage of the population.

  5. Effect of Vaccine Administration Modality on Immunogenicity and Efficacy

    PubMed Central

    Zhang, Lu; Wang, Wei; Wang, Shixia

    2016-01-01

    Summary The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: (1) features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant, and dosing; (2) individual variations among vaccine recipients; and (3) vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route, and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines. PMID:26313239

  6. New challenges in assuring vaccine quality.

    PubMed Central

    Dellepiane, N.; Griffiths, E.; Milstien, J. B.

    2000-01-01

    In the past, quality control of vaccines depended on use of a variety of testing methods to ensure that the products were safe and potent. These methods were developed for vaccines whose safety and efficacy were based on several years worth of data. However, as vaccine production technologies have developed, so have the testing technologies. Tests are now able to detect potential hazards with a sensitivity not possible a few years ago, and an increasing array of physicochemical methods allows a much better characterization of the product. In addition to sophisticated tests, vaccine regulation entails a number of other procedures to ensure safety. These include characterization of starting materials by supplier audits, cell banking, seed lot systems, compliance with the principles of good manufacturing practices, independent release of vaccines on a lot-by-lot basis by national regulatory authorities, and enhanced pre- and post-marketing surveillance for possible adverse events following immunization. These procedures help assure vaccine efficacy and safety, and some examples are given in this article. However, some contaminants of vaccines that can be detected by newer assays raise theoretical safety concerns but their presence may be less hazardous than not giving the vaccines. Thus risk-benefit decisions must be well informed and based on scientific evidence. PMID:10743279

  7. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

    MedlinePlus

    Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  8. Gulf war syndrome: could it be triggered by biological warfare-vaccines using pertussis as an adjuvant?

    PubMed

    Tournier, J-N; Jouan, A; Mathieu, J; Drouet, E

    2002-04-01

    Several recent epidemiological studies have shown that vaccinations against biological warfare using pertussis as an adjuvant were associated with the Gulf war syndrome. If such epidemiological findings are confirmed, we propose that the use of pertussis as an adjuvant could trigger neurodegeneration through induction of interleukin-1beta secretion in the brain. In turn, neuronal lesions may be sustained by stress or neurotoxic chemical combinations. Particular susceptibility for IL-1beta secretion and potential distant neuronal damage could provide an explanation for the diversity of the symptoms observed on veterans. Copyright 2002 Elsevier Science Ltd. All rights reserved.

  9. 21 CFR 510.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Biologics; products subject to license control... Biologics; products subject to license control. An animal drug produced and distributed in full conformance..., Drug, and Cosmetic Act. ...

  10. 21 CFR 510.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Biologics; products subject to license control... Biologics; products subject to license control. An animal drug produced and distributed in full conformance..., Drug, and Cosmetic Act. ...

  11. 21 CFR 510.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Biologics; products subject to license control... Biologics; products subject to license control. An animal drug produced and distributed in full conformance..., Drug, and Cosmetic Act. ...

  12. Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate.

    PubMed

    Parzych, Elizabeth M; Miura, Kazutoyo; Ramanathan, Aarti; Long, Carole A; Burns, James M

    2018-01-01

    Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multiantigen vaccine. Attempting to resolve these issues, we focused on the use of highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that a genetic fusion of the C-terminal 19-kDa fragment of merozoite surface protein 1 (MSP1 19 ) to P. falciparum MSP8 ( Pf MSP8) facilitated antigen production and folding and the induction of neutralizing antibodies to conformational B cell epitopes of MSP1 19 Here, using the Pf MSP1/8 construct, we further optimized the recombinant Pf MSP8 (r Pf MSP8) carrier by the introduction of two cysteine-to-serine substitutions (CΔS) to improve the yield of the monomeric product. We then sought to test the broad applicability of this approach using the transmission-blocking vaccine candidate Pf s25. The production of r Pf s25-based vaccines has presented challenges. Antibodies directed against the four highly constrained epidermal growth factor (EGF)-like domains of Pf s25 block sexual-stage development in mosquitoes. The sequence encoding mature Pf s25 was codon harmonized for expression in Escherichia coli We produced a r Pf s25- Pf MSP8 fusion protein [r Pf s25/8(CΔS)] as well as unfused, mature r Pf s25. r Pf s25 was purified with a modest yield but required the incorporation of refolding protocols to obtain a proper conformation. In comparison, chimeric r Pf s25/8(CΔS) was expressed and easily purified, with the Pf s25 domain bearing the proper conformation without renaturation. Both antigens were immunogenic in rabbits, inducing IgG that bound native Pf s25 and exhibited potent transmission-reducing activity. These data further demonstrate the utility of Pf MSP8 as a parasite-specific carrier protein to enhance the production of complex malaria vaccine targets. Copyright © 2017 American Society for Microbiology.

  13. 76 FR 32364 - Collaboration in Regulatory Science and Capacity To Advance Global Access to Safe Vaccines and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-06

    ...] Collaboration in Regulatory Science and Capacity To Advance Global Access to Safe Vaccines and Biologicals... and other biologicals that meet international standards. The goal of FDA's Center for Biologics... oversight of influenza and other vaccines and biologicals by supporting analysis, synthesis, and application...

  14. The establishment of surrogates and correlates of protection: Useful tools for the licensure of effective influenza vaccines?

    PubMed Central

    Ward, Brian J.; Pillet, Stephane; Charland, Nathalie; Trepanier, Sonia; Couillard, Julie; Landry, Nathalie

    2018-01-01

    ABSTRACT The search for a test that can predict vaccine efficacy is an important part of any vaccine development program. Although regulators hesitate to acknowledge any test as a true ‘correlate of protection’, there are many precedents for defining ‘surrogate’ assays. Surrogates can be powerful tools for vaccine optimization, licensure, comparisons between products and development of improved products. When such tests achieve ‘reference’ status however, they can inadvertently become barriers to new technologies that do not work the same way as existing vaccines. This is particularly true when these tests are based upon circularly-defined ‘reference’ or, even worse, proprietary reagents. The situation with inactivated influenza vaccines is a good example of this phenomenon. The most frequently used tests to define vaccine-induced immunity are all serologic assays: hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization (MN). The first two, and particularly the HI assay, have achieved reference status and criteria have been established in many jurisdictions for their use in licensing new vaccines and to compare the performance of different vaccines. However, all of these assays are based on biological reagents that are notoriously difficult to standardize and can vary substantially by geography, by chance (i.e. developing reagents in eggs that may not antigenitically match wild-type viruses) and by intention (ie: choosing reagents that yield the most favorable results). This review describes attempts to standardize these assays to improve their performance as surrogates, the dangers of over-reliance on ‘reference’ serologic assays, the ways that manufacturers can exploit the existing regulatory framework to make their products ‘look good’ and the implications of this long-established system for the introduction of novel influenza vaccines. PMID:29252098

  15. Algae-based oral recombinant vaccines

    PubMed Central

    Specht, Elizabeth A.; Mayfield, Stephen P.

    2014-01-01

    Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for “molecular pharming” in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae could be poised to become the next candidate in recombinant subunit vaccine production, as they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and systemic immune reactivity. PMID:24596570

  16. Molecular biology of Group A Streptococcus and its implications in vaccine strategies.

    PubMed

    Brahmadathan, N K

    2017-01-01

    Infections due to Streptococcus pyogenes and their complications are a problem of major concern in many countries, including India. Primary prophylaxis with benzathine penicillin is the key to control and prevent sequelae such as acute rheumatic fever and rheumatic heart disease (RF/RHD) or post-streptococcal glomerulonephritis (PSGN). Non-compliance to prophylaxis due to fear of injection and anaphylaxis is major issues in RF/RHD control in India and leads to continued high prevalence of infection and post-streptococcal sequelae. Differing reports on the efficacy of two weekly, three weekly or monthly injections raise questions on the actual dosages to be administered. Availability of more effective antibiotics with better dosages has replaced the use of penicillin; hence, companies are reluctant to manufacture penicillin preparations in India. It is in this context that a concept of a Group A streptococci vaccine is looked at and whether or not a globally designed vaccine will be useful in the Indian context. Modern molecular techniques and genomic analysis of S. pyogenes have identified many molecules as vaccine candidates among which the M-protein has attracted the most attention. High diversity of M (emm) types in endemic regions raises questions about the efficacy of such a vaccine. A recent 30-valent M-protein-based vaccine that elicits antibodies to homologous as well as non-vaccine M types looks promising. This review will discuss the genomics of S. pyogenes, the various candidate vaccine molecules and highlight their efficacy in the Indian context where control of post-streptococcal sequelae remains a challenge.

  17. Malaria vaccines and human immune responses.

    PubMed

    Long, Carole A; Zavala, Fidel

    2016-08-01

    Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. Published by Elsevier Ltd.

  18. Outer membrane vesicles as platform vaccine technology

    PubMed Central

    Stork, Michiel; van der Ley, Peter

    2015-01-01

    Abstract Outer membrane vesicles (OMVs) are released spontaneously during growth by many Gram‐negative bacteria. They present a range of surface antigens in a native conformation and have natural properties like immunogenicity, self‐adjuvation and uptake by immune cells which make them attractive for application as vaccines against pathogenic bacteria. In particular with Neisseria meningitidis, they have been investigated extensively and an OMV‐containing meningococcal vaccine has recently been approved by regulatory agencies. Genetic engineering of the OMV‐producing bacteria can be used to improve and expand their usefulness as vaccines. Recent work on meningitis B vaccines shows that OMVs can be modified, such as for lipopolysaccharide reactogenicity, to yield an OMV product that is safe and effective. The overexpression of crucial antigens or simultaneous expression of multiple antigenic variants as well as the expression of heterologous antigens enable expansion of their range of applications. In addition, modifications may increase the yield of OMV production and can be combined with specific production processes to obtain high amounts of well‐defined, stable and uniform OMV particle vaccine products. Further improvement can facilitate the development of OMVs as platform vaccine product for multiple applications. PMID:26912077

  19. 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.

  20. Economics of animal vaccination.

    PubMed

    McLeod, A; Rushton, J

    2007-08-01

    This paper describes the steps that might be used in assessing the economic justification for using vaccination to control animal disease, and the way that vaccination is financed and administered. It describes decisions that have been taken with respect to preserving international trade, and issues related to protection of livelihoods. Regardless of the motivation for vaccination, its costs can usually be shared between the public and private sectors. Cost-effective vaccination requires methods of delivery to be adapted to livestock production systems. The paper concludes by suggesting questions around the use of vaccination that would merit further economic analysis.