Science.gov

Sample records for vaccines biological products

  1. 77 FR 42319 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-18

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... lines derived from human tumors for vaccine manufacture. FDA intends to make background...

  2. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... selection of strains to be included in the influenza virus vaccine for the 2011-2012 influenza season....

  3. 75 FR 17929 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... circovirus type 1 (PCV 1) in Rotarix, a U.S. licensed vaccine manufactured by GlaxoSmithKline and...

  4. 75 FR 2876 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... selection of strains to be included in the influenza virus vaccine for the 2010 - 2011 influenza season....

  5. 75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... for protective antigen-based anthrax vaccines for a post-exposure prophylaxis indication using...

  6. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ... Person: Donald W. Jehn or Denise Royster, Center for Biologics Evaluation and Research (HFM-71), Food and... morning of April 6, 2011, the committee will meet in open session to hear updates of the research programs... Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. In...

  7. 77 FR 3780 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... Research (HFM-71), Food and Drug Administration, 1401 Rockville Pike Rockville, MD 20852, (301) 827- 0314... research program in the Laboratory of Mycobacterial Diseases and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics...

  8. 78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public...

  9. 77 FR 63839 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public...

  10. 76 FR 44016 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ... Biologics Evaluation and Research (HFM-71), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD... hear an overview of the research program in the Laboratory of Enteric and Sexually Transmitted Diseases, Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review,...

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public...

  12. 76 FR 55397 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public...

  13. 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

  14. Systems biology in vaccine design

    PubMed Central

    Six, Adrien; Bellier, Bertrand; Thomas‐Vaslin, Véronique; Klatzmann, David

    2012-01-01

    Summary Vaccines are the most effective tools to prevent infectious diseases and to minimize their impact on humans or animals. Despite the successful development of vaccines that are able to elicit potent and protective immune responses, the majority of vaccines have been so far developed empirically and mechanistic events leading to protective immune responses are often poorly understood. This hampers the development of new prophylactic as well as therapeutic vaccines for infectious diseases and cancer. Biological correlates of immune‐mediated protection are currently based on standard readout such as antibody titres and ELISPOT assays. The development of successful vaccines for difficult settings, such as infectious agents leading to chronic infection (HIV, HCV. . .) or cancer, calls for novel ‘readout systems’ or ‘correlates’ of immune‐mediated protection that would reliably predict immune responses to novel vaccines in vivo. Systems biology offers a new approach to vaccine design that is based upon understanding the molecular network mobilized by vaccination. Systems vaccinology approaches investigate more global correlates of successful vaccination, beyond the specific immune response to the antigens administered, providing new methods for measuring early vaccine efficacy and ultimately generating hypotheses for understanding the mechanisms that underlie successful immunogenicity. Using functional genomics, specific molecular signatures of individual vaccine can be identified and used as predictors of vaccination efficiency. The immune response to vaccination involves the coordinated induction of master transcription factors that leads to the development of a broad, polyfunctional and persistent immune response integrating all effector cells of the immune systems. PMID:22189033

  15. 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. PMID:18678191

  16. 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

    ...; and USSN 12/838,292, filed Jul 16, 2010; entitled ``Influenza DNA Vaccination and Methods of Use... animals increase the risk of reassortment and adaption to humans. This technology describes DNA...

  17. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  18. 78 FR 60884 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ..., the committee will meet in open session to hear an overview of the research programs in the Laboratory... Research and Review, Center for Biologics Evaluation and Review, FDA. FDA intends to make background.... 552b(c)(6)). The committee will discuss the report of the intramural research programs and...

  19. 76 FR 52668 - Vaccines and Related Biological Products Advisory Committee; Amendment of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... Laboratory of Enteric and Sexually Transmitted Diseases, Division of Bacterial, Parasitic, and Allergenic... Products Advisory Committee. This meeting was announced in the Federal Register of July 22, 2011 (76...

  20. Assessment of the impact of manufacturing changes on the physicochemical properties and biological activity of Her1-ECD vaccine during product development.

    PubMed

    Garcia Duardo, Katia; Prieto Curbelo, Yadira; Raymond Pous, Judith; Rabasa Legón, Estela Yamilet; Ramírez, Belinda Sánchez; Hernández, Kathya Rashida de la Luz; Castillo Vitoch, Adolfo

    2015-08-20

    Vaccine preparations based on the extracellular domain of Her1 (Her1-ECD) have demonstrated, in vitro and in vivo, a potent antimetastatic effect on EGFR(+) Lewis lung carcinoma model, while associated side effects were absent. The Her1-ECD is a glycoprotein with a molecular weight of 105 kDa and has 11 potential sites for N-glycosylation. Currently Her1-ECD based vaccine has been evaluated in patients with hormone refractory prostate cancer. Her1-ECD molecule used for in clinical trials was obtained from culture supernatant of HEK 293 transfectomes used the protein free culture media and is purified by immunoaffinity chromatography. In order to increase the cell growth and productivity, new defined culture media have been developed (alternative culture media) in Her1-ECD vaccine production process. In this work, a comparability study was performed to evaluate the impact of process changes in the characteristics physic-chemical and biologicals of the Her1-ECD protein and the degree of similitude between both variants. Techniques such as: SDS-PAGE, SEC-HPLC, isoelectric point, peptide mapping, mass spectrometric, SCX-HPLC, oligosaccharide map, ELISA and flow cytometric were used with this aim. Results indicated that this process change decreases the degree of sialylation of the protein but does not affect its biological activity (measured as titers of Abs and recognition for A431 cell line). PMID:26003492

  1. 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.

  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. Biological challenges to effective vaccines in the developing world.

    PubMed

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

    2015-06-19

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

  4. 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

    2015-04-01

    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

  5. Vaccines Directed Against Microorganisms or Their Products Present During Biofilm Lifestyle: Can We Make a Translation as a Broad Biological Model to Tuberculosis?

    PubMed Central

    Flores-Valdez, Mario A.

    2016-01-01

    Tuberculosis (TB) remains as a global public health problem. In recent years, experimental evidence suggesting the relevance of in vitro pellicle (a type of biofilm formed at the air-liquid interface) production as a phenotype mimicking aspects found by Mycobacterium tuberculosis-complex bacteria during in vivo infection has started to accumulate. There are still opportunities for better diagnostic tools, therapeutic molecules as well as new vaccine candidates to assist in TB control programs worldwide and particularly in less developed nations. Regarding vaccines, despite the availability of a live, attenuated strain (Mycobacterium bovis BCG) since almost a century ago, its variable efficacy and lack of protection against pulmonary and latent disease has prompted basic and applied research leading to preclinical and clinical evaluation of up to 15 new candidates. In this work, I present examples of vaccines based on whole cells grown as biofilms, or specific proteins expressed under such condition, and the effect they have shown in relevant animal models or directly in the natural host. I also discuss why it might be worthwhile to explore these approaches, for constructing and developing new vaccine candidates for testing their efficacy against TB. PMID:26834732

  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. PMID:21664680

  7. Development of pandemic influenza vaccine production capacity in Viet Nam.

    PubMed

    Hoa, L K; Hiep, L V; Be, L V

    2011-07-01

    The Institute of Vaccines and Medical Biologicals (IVAC), a state-owned vaccine manufacturer, initiated research into avian influenza vaccines in the early 1990 s in response to the threat of a highly pathogenic avian influenza pandemic. Successful results from laboratory studies on A(H5N1) influenza virus attracted seed funds and led to participation in the WHO technology transfer project to enhance influenza vaccine production in developing countries. IVAC's goal is to produce 500,000 doses of inactivated monovalent whole-virion influenza vaccine per year by 2012, and progressively increase capacity to more than 1 million doses to protect essential populations in Viet Nam in the event of an influenza pandemic. The WHO seed grants, supplemented by other international partner support, enabled IVAC to build in a very short time an influenza vaccine manufacturing plant under Good Manufacturing Practice and relevant biosafety standards, a waste treatment system and a dedicated chicken farm for high-quality eggs. Much of the equipment and instrumentation required for vaccine production has been installed and tested for functional operation. Staff have been trained on site and at specialized courses which provided comprehensive manuals on egg-based manufacturing processes and biosafety. Following process validation, clinical trials will start in 2011 and the first domestic influenza vaccine doses are expected in 2012. PMID:21684426

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2014-01-01

    A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene ‘signatures’ that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4—an orchestrator of the integrated stress response—that correlated with and predicted YF-17D CD8+ T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy. PMID:19029902

  10. Pulsed ultrasound for enhancing vaccine production.

    PubMed

    Xing, Jida; Hu, Chenxia; Ma, Allan; George, Rajan; Xing, James Z; Chen, Jie

    2015-08-01

    Hepatitis B is an infectious liver disease and vaccination is an effective way to protect individuals. We have applied mechanical wave stimulation to increase protein production. To validate our design, we used Sf9 insect cells to increase antigen fragment fusion protein expression for hepatitis B virus (HBV S1/S2). We discovered that stimulation at a frequency of 1.5 MHz, intensity of 60 mW/cm(2), for a duration of 10 minutes per day increased HBV S1/S2 production by 15%. This finding is very significant for shortening vaccine production time or increasing the yield of proteins for use as vaccines. PMID:26736715

  11. Biological and clinical developments in melanoma vaccines.

    PubMed

    Marchand, M; Brichard, V; van Baren, N; Coulie, P G

    2001-05-01

    The identification of antigens recognised on human tumours by autologous T-lymphocytes has opened the way for vaccination strategies involving defined tumour antigens. These vaccinations are therapeutic, i.e. they involve patients with detectable disease. Tumour regressions have been observed in a minority of melanoma patients in Phase I/II trials. Some of these regressions have been complete and long lasting. Improving the efficacy of therapeutic vaccines will critically depend on their capacity to trigger a robust immune response, on the development of appropriate methods to monitor these antitumour immune responses to vaccination and on a better understanding of the mechanisms used by tumours to escape immune attack. Finally, the initiation of large randomised Phase III trials will determine the impact of these vaccines on melanoma treatment. PMID:11727521

  12. Plastids: The Green Frontiers for Vaccine Production

    PubMed Central

    Waheed, Mohammad T.; Ismail, Hammad; Gottschamel, Johanna; Mirza, Bushra; Lössl, Andreas G.

    2015-01-01

    Infectious diseases pose an increasing risk to health, especially in developing countries. Vaccines are available to either cure or prevent many of these diseases. However, there are certain limitations related to these vaccines, mainly the costs, which make these vaccines mostly unaffordable for people in resource poor countries. These costs are mainly related to production and purification of the products manufactured from fermenter-based systems. Plastid biotechnology has become an attractive platform to produce biopharmaceuticals in large amounts and cost-effectively. This is mainly due to high copy number of plastids DNA in mature chloroplasts, a characteristic particularly important for vaccine production in large amounts. An additional advantage lies in the maternal inheritance of plastids in most plant species, which addresses the regulatory concerns related to transgenic plants. These and many other aspects of plastids will be discussed in the present review, especially those that particularly make these green biofactories an attractive platform for vaccine production. A summary of recent vaccine antigens against different human diseases expressed in plastids will also be presented. PMID:26635832

  13. Systems vaccinology: Enabling rational vaccine design with systems biological approaches.

    PubMed

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

    2015-09-29

    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

  14. Biological hydrogen production

    SciTech Connect

    Benemann, J.R.

    1995-11-01

    Biological hydrogen production can be accomplished by either thermochemical (gasification) conversion of woody biomass and agricultural residues or by microbiological processes that yield hydrogen gas from organic wastes or water. Biomass gasification is a well established technology; however, the synthesis gas produced, a mixture of CO and H{sub 2}, requires a shift reaction to convert the CO to H{sub 2}. Microbiological processes can carry out this reaction more efficiently than conventional catalysts, and may be more appropriate for the relatively small-scale of biomass gasification processes. Development of a microbial shift reaction may be a near-term practical application of microbial hydrogen production.

  15. Novel molecular biology approaches to acellular vaccines.

    PubMed

    Rappuoli, R; Pizza, M

    1996-01-01

    Bacterial toxins are commonly detoxified by chemical treatment in order to use them in human vaccines. We have used site-directed mutagenesis of toxin genes to obtain bacteria that produce naturally nontoxic mutants of bacterial toxins, such as pertussis toxin (PT), cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT). Genetically detoxified PT showed a superior safety and immunogenicity in animal models, phase I and phase II clinical trials, and a superior protective efficacy in the early and late stage of a phase III efficacy trial, proving in a definitive and extensive way that genetic detoxification of bacterial toxins can, and should, replace chemical treatment. The results obtained with genetically inactivated LT and CT indicate that genetic detoxification of bacterial toxins can be used not only to produce vaccines for systemic immunization that are superior to the ones produced by conventional technologies, but suggest that these type of molecules may be the prototype molecules for the design and construction of innovative vaccines with a totally new design, such as mucosally delivered preventive and therapeutic vaccines. PMID:9704103

  16. 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

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

    PubMed

    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

  18. [Production of rabies vaccine in animal diploid cells].

    PubMed

    Lucas, G; Reculard, P; Adamowicz, P; Vacher, B; Prunet, P

    1982-01-01

    Modalities for production of inactivated rabies vaccine derived from diploid hamster cell cultures are reported. The inactivated concentrated virus, purified by zonal centrifugation, is utilised for the preparation of vaccines destinated to carnivores, either in the form of monovalent vaccine or associated with distemper and canine contagious hepatitis vaccines. The inactivated concentrated virus is utilised for the preparation of bovine vaccine. The procedure is compatible with industrial production. The results concerning safety and potency tests of the experimental lots are presented. PMID:7128072

  19. 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

  20. FDA 101: Regulating Biological Products

    MedlinePlus

    ... animal, and microorganism—and may be produced by biotechnology methods. Gene-based and cellular biologics, at the ... other categories of biological products mostly produced by biotechnology methods, including: monoclonal antibodies designed as targeted therapies ...

  1. 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. PMID:26509554

  2. Workshop report: Schistosomiasis vaccine clinical development and product characteristics.

    PubMed

    Mo, Annie X; Colley, Daniel G

    2016-02-17

    A schistosomiasis vaccine meeting was organized to evaluate the utility of a vaccine in public health programs, to discuss clinical development paths, and to define basic product characteristics for desirable vaccines to be used in the context of schistosomiasis control and elimination programs. It was concluded that clinical evaluation of a schistosomiasis vaccine is feasible with appropriate trial design and tools. Some basic Preferred Product Characteristics (PPC) for a human schistosomiasis vaccine and for a veterinary vaccine for bovine use were also proposed. PMID:26721329

  3. Tetravalent DNA vaccine product as a vaccine candidate against dengue.

    PubMed

    Porter, Kevin R; Teneza-Mora, Nimfa; Raviprakash, Kanakatte

    2014-01-01

    Dengue is the most important arbovirus worldwide and is the virus that causes dengue fever and the more severe dengue hemorrhagic fever. There are four serotypes of dengue with each possessing the ability to cause disease. Developing a preventive vaccine is the most efficient and effective way to prevent these diseases, and because immunity to one serotype does not protect against the other serotypes, a vaccine must provide tetravalent protection. We used DNA immunization as a platform to develop a tetravalent vaccine. In this chapter, we describe the laboratory, regulatory, and clinical methodology for evaluating a candidate tetravalent vaccine in a Phase 1 clinical trial. PMID:24715294

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed

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

    1995-01-01

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

  7. Biological Effects of Listeriolysin O: Implications for Vaccination

    PubMed Central

    Hernández-Flores, K. G.; Vivanco-Cid, H.

    2015-01-01

    Listeriolysin O (LLO) is a thiol-activated cholesterol-dependent pore-forming toxin and the major virulence factor of Listeria monocytogenes (LM). Extensive research in recent years has revealed that LLO exerts a wide array of biological activities, during the infection by LM or by itself as recombinant antigen. The spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression, intracellular calcium oscillations, and proinflammatory activity. In addition, LLO is a highly immunogenic toxin and the major target for innate and adaptive immune responses in different animal models and humans. Recently, the crystal structure of LLO has been published in detail. Here, we review the structure-function relationship for this fascinating microbial molecule, highlighting the potential uses of LLO in the fields of biomedicine and biotechnology, particularly in vaccination. PMID:25874208

  8. Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

    PubMed Central

    Singh, Sarman; Singh, Pragati

    2015-01-01

    BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine. PMID:25694828

  9. 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. PMID:23015521

  10. Regulatory expectations during product development for tumour vaccines.

    PubMed

    Kawakami, K; Puri, R K

    2004-01-01

    Among various approaches for the treatment of cancer, tumour vaccines stimulate the host immune response against cancer and produce local inflammation that may result in the regression of existing tumour in the body. Therapeutic tumour vaccines may generally be grouped into cellular vaccines, synthetic peptides, purified or recombinant proteins, and multi-antigen preparations including shed, or secreted antigens or cell lysates. While no tumour vaccines have been licensed by the U.S. Food and Drug Administration (FDA), a large number of products and approaches are being developed and numerous clinical trials are currently ongoing. In this article, we summarize regulatory issues associated with different types of tumour vaccines. The step-wise approach to regulatory requirements including current good manufacturing practices (cGMPs) and characterization of these vaccines at various stages of product development is discussed. PMID:15603183

  11. Vector Design for Improved DNA Vaccine Efficacy, Safety and Production

    PubMed Central

    Williams, James A.

    2013-01-01

    DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery. This review summarizes complementary vector design innovations that, when combined with leading delivery platforms, further enhance DNA vaccine performance. These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes. Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy. PMID:26344110

  12. 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. PMID:19717312

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

    PubMed Central

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

    2014-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  15. DNA Virus Vectors for Vaccine Production in Plants: Spotlight on Geminiviruses

    PubMed Central

    Hefferon, Kathleen L.

    2014-01-01

    Plants represent a safe, efficacious and inexpensive production platform by which to provide vaccines and other therapeutic proteins to the world’s poor. Plant virus expression vector technology has rapidly become one of the most popular methods to express pharmaceutical proteins in plants. This review discusses several of the state-of-the-art plant expression systems based upon geminiviruses that have been engineered for vaccine production. An overview of the advantages of these small, single-stranded DNA viruses is provided and comparisons are made with other virus expression systems. Advances in the design of several different geminivirus vectors are presented in this review, and examples of vaccines and other biologics generated from each are described. PMID:26344750

  16. IRRIGATION FOR VACCINE PRODUCTION IN PHARMACEUTICAL TOBACCO

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  17. Monoclonal Antibodies to Shigella Lipopolysaccharide Are Useful for Vaccine Production.

    PubMed

    Lin, Jisheng; Smith, Mark A; Benjamin, William H; Kaminski, Robert W; Wenzel, Heather; Nahm, Moon H

    2016-08-01

    There is a significant need for an effective multivalent Shigella vaccine that targets the most prevalent serotypes. Most Shigella vaccines under development utilize serotype-specific lipopolysaccharides (LPSs) as a major component based on protection and epidemiological data. As vaccine formulations advance from monovalent to multivalent, assays and reagents need to be developed to accurately and reproducibly quantitate the amount of LPSs from multiple serotypes in the final product. To facilitate this effort, we produced 36 hybridomas that secrete monoclonal antibodies (MAbs) against the O antigen on the LPS from Shigella flexneri 2a, Shigella flexneri 3a, and Shigella sonnei We used six of these monoclonal antibodies for an inhibition enzyme-linked immunosorbent assay (iELISA), measuring LPSs with high sensitivity and specificity. It was also demonstrated that the Shigella serotype-specific MAbs were useful for bacterial surface staining detected by flow cytometry. These MAbs are also useful for standardizing the serum bactericidal assay (SBA) for Shigella Functional assays, such as the in vitro bactericidal assay, are necessary for vaccine evaluation and may serve as immunological correlates of immunity. An S. flexneri 2a-specific monoclonal antibody killed S. flexneri 2b isolates, suggesting that S. flexneri 2a LPS may induce cross-protection against S. flexneri 2b. Overall, the Shigella LPS-specific MAbs described have potential utility to the vaccine development community for assessing multivalent vaccine composition and as a reliable control for multiple immunoassays used to assess vaccine potency. PMID:27280622

  18. 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

  19. 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

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

    SciTech Connect

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

    2011-09-22

    The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures

  1. Comparative biological activities of acellular pertussis vaccines produced by Kitasato.

    PubMed

    Watanabe, M; Izumiya, K; Sato, T; Yoshino, K; Nakagawa, N; Ohoishi, M; Hoshino, M

    1991-04-01

    The quality of 14 lots of acellular pertussis-diphtheria-tetanus (AC-PDT) vaccines manufactured by the Kitasato Institute during the period 1987-1990 were investigated. The geometric means of HSU, LPU, and BWDU were 0.078, 0.257, and 7.33 per ml respectively. The potency was higher than 14 IU per ml. These results indicated the consistency of the Kitasato AC-PDT vaccines. The antibody response to the AC-PDT vaccines was measured in primary and secondary vaccinated mice by ELISA. IgG antibody response to FHA and PT was obtained in all immunized mice (P less than 0.001) after the primary injection. In contrast, IgG antibody response to fimbriae 2 showed a significant titer rise (P less than 0.001) after the booster injection. The results indicated that the Kitasato AC-P vaccines consisted of protein, PT and FHA as the major antigens, and a little agglutinogen as the minor antigen. PMID:1798236

  2. Antigenicity of Streptococcus agalactiae extracellular products and vaccine efficacy.

    PubMed

    Pasnik, D J; Evans, J J; Panangala, V S; Klesius, P H; Shelby, R A; Shoemaker, C A

    2005-04-01

    Streptococcus agalactiae is a major bacterial pathogen that is the cause of serious economic losses in many species of freshwater, marine and estuarine fish worldwide. A highly efficacious S. agalactiae vaccine was developed using extracellular products (ECP) and formalin-killed whole cells of S. agalactiae. The vaccine efficacy following storage of S. agalactiae ECP and formalin-killed S. agalactiae cells at 4 degrees C for 1 year was determined. The stored ECP containing S. agalactiae formalin-killed cells failed to prevent morbidity and mortality among the vaccinated fish, and the relative percentage survival was 29. Serum antibody responses of the stored ECP and freshly prepared ECP against soluble whole cell extract of S. agalactiae indicated that significantly less antibody was produced in fish immunized with stored ECP and S. agalactiae cells than in those fish immunized with freshly prepared ECP and S. agalactiae cells at day 31 post-vaccination. Silver staining of sodium dodecyl sulphate-polyacrylamide gels and immunostaining of Western blots with tilapia antiserum to S. agalactiae revealed that predominant 54 and 55 kDa bands were present in the freshly prepared ECP fraction. The 55 kDa band was absent from the stored ECP and new bands below 54 kDa appeared on the Western blot. The results of this study on S. agalactiae ECP provide evidence for a correlation between protection and antibody production to ECP and for the importance of the 55 kDa ECP antigen for vaccine efficacy. PMID:15813862

  3. Vaccinations

    MedlinePlus

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

  4. Vaccine production: upstream processing with adherent or suspension cell lines.

    PubMed

    Genzel, Yvonne; Rödig, Jana; Rapp, Erdmann; Reichl, Udo

    2014-01-01

    The production of viral vaccines in cell culture can be accomplished with primary, diploid, or continuous (transformed) cell lines. Each cell line, each virus type, and each vaccine preparation require the specific design of upstream and downstream processing. Media have to be selected as well as production vessels, cultivation conditions, and modes of operation. Many viruses only replicate to high titers in adherently growing cells, but similar to processes established for recombinant protein production, an increasing number of suspension cell lines is being evaluated for future use. Here, we describe key issues to be considered for the establishment of large-scale virus production in bioreactors. As an example upstream processing of cell culture-derived influenza virus production is described in more detail for adherently growing and for suspension cells. In particular, use of serum-containing, serum-free, and chemically defined media as well as choice of cultivation vessel are considered. PMID:24297427

  5. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 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...

  6. 9 CFR 114.4 - Identification 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 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...

  7. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 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...

  8. 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...

  9. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 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...

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

    PubMed Central

    Cuccui, Jon; Wren, Brendan

    2016-01-01

    Objectives 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. Key findings 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

  11. [Viral safety of biological medicinal products].

    PubMed

    Stühler, A; Blümel, J

    2014-10-01

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

  12. 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

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

    PubMed

    Lee, Bruce Y; Burke, Donald S

    2010-04-01

    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

  14. Biological production of products from waste gases

    DOEpatents

    Gaddy, James L.

    2002-01-22

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

  15. 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

  16. Patent landscape for biological hydrogen production.

    PubMed

    Levin, David B; Lubieniechi, Simona

    2013-12-01

    Research and development of biological hydrogen production have expanded significantly in the past decade. Production of renewable hydrogen from agricultural, forestry, or other organic waste streams offers the possibility to contribute to hydrogen production capacity with no net, or at least with lower, greenhouse gas emissions. Significant improvements in the volumetric or molar yields of hydrogen production have been accomplished through genetic engineering of hydrogen synthesizing microorganisms. Although no commercial scale renewable biohydrogen production facilities are currently in operation, a few pilot scale systems have been demonstrated successfully, and while industrial scale production of biohydrogen still faces a number of technical and economic barriers, understanding the patent landscape is an important step in developing a viable commercialization strategy. In this paper, we review patents filed on biological hydrogen production. Patents on biohydrogen production from both the Canadian and American Patents databases were classified into three main groups: (1) patents for biological hydrogen by direct photolysis; (2) patents for biological hydrogen by dark fermentation; and (3) patents for process engineering for biological hydrogen production. PMID:23521705

  17. 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. PMID:27523619

  18. Vaccines

    MedlinePlus Videos and Cool Tools

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

  19. Models of risk assessments for biologicals or related products in the European Union.

    PubMed

    Moos, M

    1995-12-01

    In the context of veterinary biologicals, environmental risk assessment means the evaluation of the risk to human health and the environment (which includes plants and animals) connected with the release of such products. The following categories or types of veterinary biologicals can be distinguished: non-genetically modified organisms (non-GMOs) (inactivated/live) GMOs (inactivated/live) carrier products related products (e.g. non-specific "inducers'). Suitable models used in risk assessment for these products should aim to identify all possible adverse effects. A good working model should lead, at least, to a qualitative judgement on the environmental risk of the biological product (e.g. negligible, low, medium, severe, unacceptable). Quantifiable outcomes are rare; therefore, the producer of a biological product and the European control authorities should accept only models which are based on testable points and which are relevant to the type of product and its instructions for use. In view of animal welfare aspects, models working without animals should be preferred. In recent years, some of these methods have been integrated into safety tests described in European Union Directives and in monographs of the European Pharmacopoeia. By reviewing vaccine/registration problems (e.g. Aujeszky's disease live vaccine for pigs, and vaccinia-vectored rabies vaccine), several models used in risk assessment are demonstrated and discussed. PMID:8639943

  20. 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. PMID:24798081

  1. Human adenovirus-vectored foot-and-mouth disease vaccines: establishment of a vaccine product profile through in vitro testing.

    PubMed

    Brake, D A; McIlhaney, M; Miller, T; Christianson, K; Keene, A; Lohnas, G; Purcell, C; Neilan, J; Schutta, C; Barrera, J; Burrage, T; Brough, D E; Butman, B T

    2012-01-01

    Next generation, foot-and-mouth disease (FMD) molecular vaccines based on replication deficient human adenovirus serotype 5 viral vectored delivery of FMD capsid genes (AdFMD) are being developed by the United States Dept. of Homeland Security and industry partners. The strategic goal of this program is to develop AdFMD licensed vaccines for the USA National Veterinary Stockpile for use, if needed, as emergency response tools during an FMD outbreak. This vaccine platform provides a unique opportunity to develop a set of in vitro analytical parameters to generate an AdFMD vaccine product profile to replace the current lot release test for traditional, inactivated FMD vaccines that requires FMDV challenge in livestock. The possibility of an indirect FMD vaccine potency test based on a serological alternative was initially investigated for a lead vaccine candidate, Adt.A24. Results show that serum virus neutralization (SVN) based serology testing for Adt.A24 vaccine lot release is not feasible, at least not in the context of vaccine potency assessment at one week post-vaccination. Thus, an in vitro infectious titer assay (tissue culture infectious dose 50, TCID50) which measures FMD infectious (protein expression) titer was established. Pre-validation results show acceptable assay variability and linearity and these data support further studies to validate the TCID50 assay as a potential potency release test. In addition, a quantitative physiochemical assay (HPLC) and three immunochemical assays (Fluorescent Focus-Forming Unit (FFU); tissue culture expression dose 50 (TCED50); Western blot) were developed for potential use as in vitro assays to monitor AdFMD vaccine lot-to-lot consistency and other potential applications. These results demonstrate the feasibility of using a traditional modified-live vaccine virus infectivity assay in combination with a set of physiochemical and immunochemical tests to build a vaccine product profile that will ensure the each Ad

  2. Biological production of organic compounds

    DOEpatents

    Yu, Jianping; Paddock, Troy; Carrieri, Damian; Maness, Pin-Ching; Seibert, Michael

    2016-04-12

    Strains of cyanobacteria that produce high levels of alpha ketoglutarate (AKG) and pyruvate are disclosed herein. Methods of culturing these cyanobacteria to produce AKG or pyruvate and recover AKG or pyruvate from the culture are also described herein. Nucleic acid sequences encoding polypeptides that function as ethylene-forming enzymes and their use in the production of ethylene are further disclosed herein. These nucleic acids may be expressed in hosts such as cyanobacteria, which in turn may be cultured to produce ethylene.

  3. Use of viral vectors for vaccine production in plants.

    PubMed

    Cañizares, M Carmen; Nicholson, Liz; Lomonossoff, George P

    2005-06-01

    The small size of plant viral genomes, the ease with which they can be manipulated, and the simplicity of the infection process is making the viral vectors an attractive alternative to the transgenic systems for the expression of foreign proteins in plants. One use of these virus expression systems is for vaccine production. There are two basic types of viral system that have been developed for the production of immunogenic peptides and proteins in plants: epitope presentation and polypeptide expression systems. In this review, we discuss advances made in this field. PMID:15877604

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

    PubMed Central

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

    2015-01-01

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

  5. Biological challenges and technological opportunities for respiratory syncytial virus vaccine development.

    PubMed

    Graham, Barney S

    2011-01-01

    Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV-induced adaptive immunity to prevent reinfection, history of RSV vaccine-enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to protect infants from severe RSV disease. Therefore, the immunological goals for vaccine development are to induce effective neutralizing antibody to prevent infection and to avoid inducing T-cell response patterns associated with enhanced disease. Live-attenuated RSV and replication-competent chimeric viruses are in advanced clinical trials. Gene-based strategies, which can control the specificity and phenotypic properties of RSV-specific T-cell responses utilizing replication-defective vectors and which may improve on immunity from natural infection, are progressing through preclinical testing. Atomic level structural information on RSV envelope glycoproteins in complex with neutralizing antibodies is guiding design of new vaccine antigens that may be able to elicit RSV-specific antibody responses without induction of RSV-specific T-cell responses. These new technologies may allow development of vaccines that can protect against RSV-mediated disease in infants and establish a new immunological paradigm in the host to achieve more durable protection against reinfection. PMID:21198670

  6. 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 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form,...

  7. 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 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form,...

  8. 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 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form,...

  9. 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 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form,...

  10. 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 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form,...

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

    USGS Publications Warehouse

    Anderson, D.P.

    1981-01-01

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

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

    PubMed

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-01

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process. PMID:26430814

  13. Synthetic biology of fungal natural products

    PubMed Central

    Mattern, Derek J.; Valiante, Vito; Unkles, Shiela E.; Brakhage, Axel A.

    2015-01-01

    Synthetic biology is an ever-expanding field in science, also encompassing the research area of fungal natural product (NP) discovery and production. Until now, different aspects of synthetic biology have been covered in fungal NP studies from the manipulation of different regulatory elements and heterologous expression of biosynthetic pathways to the engineering of different multidomain biosynthetic enzymes such as polyketide synthases or non-ribosomal peptide synthetases. The following review will cover some of the exemplary studies of synthetic biology in filamentous fungi showing the capacity of these eukaryotes to be used as model organisms in the field. From the vast array of different NPs produced to the ease for genetic manipulation, filamentous fungi have proven to be an invaluable source for the further development of synthetic biology tools. PMID:26284053

  14. Standardization for natural product synthetic biology.

    PubMed

    Zhao, Huimin; Medema, Marnix H

    2016-08-27

    Standardization is one of the foundational features of modern-day engineering, and the use of standardized parts and processes is a key element that distinguishes bona fide synthetic biology from traditional genetic engineering. Here, we discuss the role of standardization in natural product synthetic biology, focusing on standardization of data on biosynthetic pathways and gene clusters, as well as the role of standardization in the process of biosynthetic gene cluster engineering. PMID:27313083

  15. 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

  16. 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

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

    PubMed

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

    2015-01-01

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

  18. 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... § 112.6 Packaging biological products. (a) Each multiple-dose final container of a biological product... equipment. (e) Final containers of biological product prepared at a licensed establishment, or imported,...

  19. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Packaging biological products. 112.6... § 112.6 Packaging biological products. (a) Each multiple-dose final container of a biological product... equipment. (e) Final containers of biological product prepared at a licensed establishment, or imported,...

  20. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Packaging biological products. 112.6... § 112.6 Packaging biological products. (a) Each multiple-dose final container of a biological product... equipment. (e) Final containers of biological product prepared at a licensed establishment, or imported,...

  1. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Packaging biological products. 112.6... § 112.6 Packaging biological products. (a) Each multiple-dose final container of a biological product... equipment. (e) Final containers of biological product prepared at a licensed establishment, or imported,...

  2. Do biological medicinal products pose a risk to the environment?: a current view on ecopharmacovigilance.

    PubMed

    Kühler, Thomas C; Andersson, Mikael; Carlin, Gunnar; Johnsson, Ann; Akerblom, Lennart

    2009-01-01

    The occurrence of active pharmaceutical substances in the environment is of growing concern. The vast majority of the compounds in question are of low molecular weight, intended for oral use and designed to tolerate, for example, the digestive enzymes in the upper alimentary tract, the harsh milieus found in the acidic stomach, or the microbe rich intestine. Accordingly, these xenobiotic compounds may, due to their inherent biological activity, constitute a risk to the environment. Biological medicinal products, for example recombinant human insulin or monoclonal antibodies, however, are different. They are primarily made up of oligomers or polymers of amino acids, sugars or nucleotides and are thus readily metabolized. They are therefore generally not considered to pose any risk to the environment. Certain classes of biological medicinal products, however, are associated with specific safety issues. Genetically modified organisms as vectors in vaccines or in gene therapy products have attracted much attention in this regard. Issues include the degree of attenuation of the live recombinant vaccine, replication restrictions of the vaccine vector, alteration of the host and tissue tropism of the vector, the possibility of reversion to virulence, and risk to the ecosystem. In this review we discuss the fate and the potential environmental impact of biological medicinal products following clinical use from an ecopharmacovigilance point of view, and review relevant policy documents and regulatory statements. PMID:19810773

  3. [Public laboratories for vaccine production: a new paradigm].

    PubMed

    Homma, A; di Fabio, J L; de Quadros, C

    1998-10-01

    In Latin America and the Caribbean, public laboratories that produce vaccines have contributed in varying degrees to the control and eradication of vaccine-preventable diseases, and several of them are manufacturing vaccines that are routinely applied in national immunization programs, such as the vaccine against tuberculosis (made with the bacillus of Calmette-Guérin, BCG), the triple vaccine against diphtheriatetanus-pertussis (DTP), tetanus toxoid (TT), the vaccine against measles and the oral vaccine against polio. Thanks to recent scientific strides, one can foresee an important increase in the number of safe and effective vaccines that will be available in the near future for use in routine vaccination programs. However, there are high costs involved in developing such vaccines and in protecting the intellectual property rights involved, and few laboratories in Latin America have the technical capacity to research and develop these vaccines. Such factors will affect the speed with which they are assimilated into vaccination programs in countries of the Region. Currently, public laboratories that manufacture vaccines in the Region are not equipped to compete in this new scenario and run the risk of being completely outmarketed. Thus, they must radically change their style of management and their scientific and technical capabilities, backed by a commitment from governments to improve and strengthen those political and financial aspects that can assure that national laboratories participate in the sustainable supply of vaccines to immunization programs, as well as in researching, developing, and producing new vaccines. PMID:9924504

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  5. Beware When Buying "All Natural" Erectile Dysfunction Products

    MedlinePlus Videos and Cool Tools

    ... search Popular Content Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics ... Area Product Areas back Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics ...

  6. [VACCINES].

    PubMed

    Bellver Capella, Vincente

    2015-10-01

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

  7. Vaccines

    MedlinePlus Videos and Cool Tools

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

  8. 9 CFR 114.18 - Reprocessing of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator...

  9. 9 CFR 114.17 - Rebottling of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator...

  10. 9 CFR 114.18 - Reprocessing 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 Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator...

  11. 9 CFR 114.17 - Rebottling of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator...

  12. 9 CFR 114.18 - Reprocessing 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 Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator...

  13. 9 CFR 114.18 - Reprocessing of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator...

  14. 9 CFR 114.17 - Rebottling 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 Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator...

  15. 9 CFR 114.17 - Rebottling of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator...

  16. 9 CFR 114.18 - Reprocessing of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator...

  17. 9 CFR 114.17 - Rebottling 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 Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator...

  18. Assessment of tuberculosis infection during treatment with biologic agents in a BCG-vaccinated pediatric population.

    PubMed

    Atikan, Basak Yildiz; Cavusoglu, Cengiz; Dortkardesler, Merve; Sozeri, Betul

    2016-02-01

    Biologic therapies, such as tumor necrosis factor-alpha (TNF-α) blockers, are commonly used to treat rheumatological diseases in childhood. Screening patients for tuberculosis (TB) is highly recommended before starting therapy with TNF-α blockers. Despite appropriate screening, TB still remains a problem in patients receiving anti-TNF therapy in countries where TB is not endemic. TB in anti-TNF-treated patients is often diagnosed late due to altered presentation, and this delay results in high morbidity and mortality with a high proportion of extrapulmonary and disseminated disease. The aim of this study is to show the course of TB disease in children who are on biologic therapy, in an era where many of the children are BCG-vaccinated and TB is intermediately endemic. We recruited 71 patients with several types of inflammatory diseases. Six of them had a positive test result during TB screening and began taking isoniazid (INH) prophylactically. During the 3 years of follow-up, none of these patients developed TB disease. Biologic agents can be safely used in a BCG-vaccinated pediatric population, as long as patients are closely monitored to ensure that any cases of TB will be detected early. PMID:25515621

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

    PubMed

    Monahan, T R

    2001-12-15

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

  20. 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

  1. 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... Applicability § 113.3 Sampling of biological products. Each licensee and permittee shall furnish representative samples of each serial or subserial of a biological product manufactured in the United States or...

  2. 9 CFR 103.3 - Shipment 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 Shipment of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.3 Shipment of experimental biological products. Except as provided in this section, no person shall ship or deliver...

  3. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Sampling of biological products. 113.3... Applicability § 113.3 Sampling of biological products. Each licensee and permittee shall furnish representative samples of each serial or subserial of a biological product manufactured in the United States or...

  4. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  5. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 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...

  6. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  7. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  8. 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...

  9. 9 CFR 103.3 - Shipment 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 Shipment of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.3 Shipment of experimental biological products. Except as provided in this section, no person shall ship or deliver...

  10. 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... Applicability § 113.3 Sampling of biological products. Each licensee and permittee shall furnish representative samples of each serial or subserial of a biological product manufactured in the United States or...

  11. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 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...

  12. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Shipment of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.3 Shipment of experimental biological products. Except as provided in this section, no person shall ship or deliver...

  13. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Sampling of biological products. 113.3... Applicability § 113.3 Sampling of biological products. Each licensee and permittee shall furnish representative samples of each serial or subserial of a biological product manufactured in the United States or...

  14. 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...

  15. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  16. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 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...

  17. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  18. 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...

  19. 9 CFR 113.50 - Ingredients 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 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...

  20. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Sampling of biological products. 113.3... Applicability § 113.3 Sampling of biological products. Each licensee and permittee shall furnish representative samples of each serial or subserial of a biological product manufactured in the United States or...

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

    PubMed

    2015-06-12

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

  2. Synthetic Biological Approaches to Natural Product Biosynthesis

    PubMed Central

    Winter, Jaclyn M; Tang, Yi

    2012-01-01

    Small molecules produced in Nature continue to be an inspiration for the development of new therapeutic agents. These natural products possess exquisite chemical diversity, which gives rise to their wide range of biological activities. In their host organism, natural products are assembled and modified by dedicated biosynthetic pathways that Nature has meticulously developed. Often times, the complex structures or chemical modifications instated by these pathways are difficult to replicate using traditional synthetic methods. An alternative approach for creating or enhancing the structural variation of natural products is through combinatorial biosynthesis. By rationally reprogramming and manipulating the biosynthetic machinery responsible for their production, unnatural metabolites that were otherwise inaccessible can be obtained. Additionally, new chemical structures can be synthesized or derivatized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed unnatural metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds. PMID:22221832

  3. [Vaccination perspectives].

    PubMed

    Saliou, P; Plotkin, S

    1994-01-01

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

  4. Production of Chikungunya Virus-Like Particles and Subunit Vaccines in Insect Cells.

    PubMed

    Metz, Stefan W; Pijlman, Gorben P

    2016-01-01

    Chikungunya virus is a reemerging human pathogen that causes debilitating arthritic disease in humans. Like dengue and Zika virus, CHIKV is transmitted by Aedes mosquitoes in an epidemic urban cycle, and is now rapidly spreading through the Americas since its introduction in the Caribbean in late 2013. There are no licensed vaccines or antiviral drugs available, and only a few vaccine candidates have passed Phase I human clinical trials. Using recombinant baculovirus expression technology, we have generated CHIKV glycoprotein subunit and virus-like particle (VLP) vaccines that are amenable to large scale production in insect cells. These vaccines, in particular the VLPs, have shown high immunogenicity and protection against CHIKV infection in different animal models of CHIKV-induced disease. Here, we describe the production, purification, and characterization of these potent CHIKV vaccine candidates. PMID:27233282

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

    PubMed Central

    Philbin, Victoria Jane; Levy, Ofer

    2009-01-01

    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 (TLRs), nucleotide oligomerization domain-like receptors (NLRs), retinoic acid inducible gene-like receptors (RLRs) and C-type lectin receptors (CLRs). 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 co-stimulatory function, and thus PRRs 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 (Alum) whose adjuvant activity depends on its ability to activate a cytosolic protein complex known as the Nacht Domain Leucine-Rich Repeat and PYD-Containing Protein 3 (NALP3) inflammasome leading to IL-1ß 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 with special emphasis on developmental expression in the fetus, newborn and infant and its implications for the design of more effective neonatal and infant vaccines. PMID:19918215

  6. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Biological products and related terms. 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS § 101.3 Biological products and related...

  7. 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...

  8. 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 AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.6 Packaging biological products....

  9. Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and plain 2009–10 seasonal influenza vaccines in rheumatoid arthritis patients on biologicals

    PubMed Central

    Milanetti, F; Germano, V; Nisini, R; Donatelli, I; Di Martino, A; Facchini, M; Ferlito, C; Cappella, A; Crialesi, D; Caporuscio, S; Biselli, R; Rossi, F; Salemi, S; D'Amelio, R

    2014-01-01

    Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009–10 influenza season, the safety and immunogenicity of co-administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti-tumour necrosis factor (TNF)-α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1-A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)-γ-, TNF-α- or interleukin (IL)-17A-secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine-producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals. PMID:24666311

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

    PubMed Central

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

    2015-01-01

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

  11. Cattle tick vaccines: many candidate antigens, but will a commercially viable product emerge?

    PubMed

    Guerrero, Felix D; Miller, Robert J; Pérez de León, Adalberto A

    2012-05-01

    The cattle tick, Rhipicephalus microplus, is arguably the world's most economically important external parasite of cattle. Sustainable cattle tick control strategies are required to maximise the productivity of cattle in both large production operations and small family farms. Commercially available synthetic acaricides are commonly used in control and eradication programs, but indiscriminate practices in their application have resulted in the rapid evolution of resistance among populations in tropical and subtropical regions where the invasive R. microplus thrives. The need for novel technologies that could be used alone or in combination with commercially available synthetic acaricides is driving a resurgence of cattle tick vaccine discovery research efforts by various groups globally. The aim is to deliver a next-generation vaccine that has an improved efficacy profile over the existing Bm86-based cattle tick vaccine product. We present a short review of these projects and offer our opinion on what constitutes a good target antigen and vaccine, and what might influence the market success of candidate vaccines. The previous experience with Bm86-based vaccines offers perspective on marketing and producer acceptance aspects that a next-generation cattle tick vaccine product must meet for successful commercialisation. PMID:22549026

  12. Soybean Seeds: A Practical Host for the Production of Functional Subunit Vaccines

    PubMed Central

    Hudson, Laura C.; Bost, Kenneth L.; Piller, Kenneth J.

    2014-01-01

    Soybean seeds possess several inherent qualities that make them an ideal host for the production of biopharmaceuticals when compared with other plant-based and non-plant-based recombinant expression systems (e.g., low cost of production, high protein to biomass ratio, long-term stability of seed proteins under ambient conditions, etc.). To demonstrate the practicality and feasibility of this platform for the production of subunit vaccines, we chose to express and characterize a nontoxic form of S. aureus enterotoxin B (mSEB) as a model vaccine candidate. We show that soy-mSEB was produced at a high vaccine to biomass ratio and represented ~76 theoretical doses of human vaccine per single soybean seed. We localized the model vaccine candidate both intracellularly and extracellularly and found no difference in mSEB protein stability or accumulation relative to subcellular environment. We also show that the model vaccine was biochemically and immunologically similar to native and recombinant forms of the protein produced in a bacterial expression system. Immunization of mice with seed extracts containing mSEB mounted a significant immune response within 14 days of the first injection. Taken together, our results highlight the practicality of soybean seeds as a potential platform for the production of functional subunit vaccines. PMID:24822195

  13. Soybean seeds: a practical host for the production of functional subunit vaccines.

    PubMed

    Hudson, Laura C; Garg, Renu; Bost, Kenneth L; Piller, Kenneth J

    2014-01-01

    Soybean seeds possess several inherent qualities that make them an ideal host for the production of biopharmaceuticals when compared with other plant-based and non-plant-based recombinant expression systems (e.g., low cost of production, high protein to biomass ratio, long-term stability of seed proteins under ambient conditions, etc.). To demonstrate the practicality and feasibility of this platform for the production of subunit vaccines, we chose to express and characterize a nontoxic form of S. aureus enterotoxin B (mSEB) as a model vaccine candidate. We show that soy-mSEB was produced at a high vaccine to biomass ratio and represented ~76 theoretical doses of human vaccine per single soybean seed. We localized the model vaccine candidate both intracellularly and extracellularly and found no difference in mSEB protein stability or accumulation relative to subcellular environment. We also show that the model vaccine was biochemically and immunologically similar to native and recombinant forms of the protein produced in a bacterial expression system. Immunization of mice with seed extracts containing mSEB mounted a significant immune response within 14 days of the first injection. Taken together, our results highlight the practicality of soybean seeds as a potential platform for the production of functional subunit vaccines. PMID:24822195

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

    PubMed

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

    2011-07-01

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

  15. 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

  16. Plasmid DNA Vaccine vector design: impact on efficacy, safety and upstream production

    PubMed Central

    Williams, James A; Carnes, Aaron E; Hodgson, Clague P

    2009-01-01

    Critical molecular and cellular biological factors impacting design of licensable DNA vaccine vectors that combine high yield and integrity during bacterial production with increased expression in mammalian cells are reviewed. Food and Drug Administration (FDA), World Health Organization (WHO) and European Medical Agencies (EMEA) regulatory guidance’s are discussed, as they relate to vector design and plasmid fermentation. While all new vectors will require extensive preclinical testing to validate safety and performance prior to clinical use, regulatory testing burden for follow-on products can be reduced by combining carefully designed synthetic genes with existing validated vector backbones. A flowchart for creation of new synthetic genes, combining rationale design with bioinformatics, is presented. The biology of plasmid replication is reviewed, and process engineering strategies that reduce metabolic burden discussed. Utilizing recently developed low metabolic burden seed stock and fermentation strategies, optimized vectors can now be manufactured in high yields exceeding 2 g/L, with specific plasmid yields of 5% total dry cell weight. PMID:19233255

  17. 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)

  18. Systems Biology of Microbial Exopolysaccharides Production

    PubMed Central

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran. PMID:26734603

  19. Systems Biology of Microbial Exopolysaccharides Production.

    PubMed

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran. PMID:26734603

  20. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-12-01

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

  1. Chemical and biological production of cyclotides

    PubMed Central

    Li, Yilong; Bi, Tao; Camarero, Julio A.

    2016-01-01

    Cyclotides are fascinating naturally occurring micro-proteins (≈30 residues long) present in several plant families, and display various biological properties such as protease inhibitory, anti-microbial, insecticidal, cytotoxic, anti-HIV and hormone-like activities. Cyclotides share a unique head-to-tail circular knotted topology of three disulfide bridges, with one disulfide penetrating through a macrocycle formed by the two other disulfides and interconnecting peptide backbones, forming what is called a cystine knot topology. This cyclic cystine knot (CCK) framework gives the cyclotides exceptional rigidity, resistance to thermal and chemical denaturation, and enzymatic stability against degradation. Interestingly, cyclotides have been shown to be orally bioavailable, and other cyclotides have been shown to cross the cell membranes. Moreover, recent reports have also shown that engineered cyclotides can be efficiently used to target extracellular and intracellular protein-protein interactions, therefore making cyclotides ideal tools for drug development to selectively target protein-protein interactions. In this work we will review all the available methods for production of these interesting proteins using chemical or biological methods. PMID:27064329

  2. IRRIGATION TO MAXIMIZE VACCINE ANTIGEN PRODUCTION IN PHARMACEUTICAL TOBACCO

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Production of Rice Seed-Based Allergy Vaccines.

    PubMed

    Takagi, Hidenori; Takaiwa, Fumio

    2016-01-01

    Recombinant hypoallergenic derivative is the next generation of tolerogen replacing the natural allergen extract to increase safety and efficacy. Japanese cedar pollinosis is the predominant seasonal allergy disease in Japan. A rice seed-based oral vaccine containing the recombinant hypoallergens derived from these allergens was developed. Efficacy of this rice-based allergy vaccine was evaluated by oral administration in animal models. PMID:27076162

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

    PubMed Central

    2014-01-01

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

  5. 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.

  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. 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

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

    PubMed

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

    2011-07-01

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

  9. 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

  10. Prokaryotic Production of Virus-Like Particle Vaccine of Betanodavirus.

    PubMed

    Xie, Junfeng; Huang, Runqing; Lai, Yuxiong

    2016-01-01

    Betanodaviruses are the causative agents of viral nervous necrosis (VNN), a serious disease of cultured marine fish worldwide. To control this disease, vaccines of subunit capsid proteins (recombinant proteins or peptides), inactivated viruses, and virus-like particles (VLPs) were developed. VLP, which is highly similar to the wild-type virus in virion structure and contains no viral genome, was proved as one of the good and safe vaccines that can activate humoral immune response in the long term and induce cellular and innate immunities in the early stage post-immunization. The VLP vaccines can be expressed in vitro either by Baculovirus-based or yeast-based eukaryotic system or by bacterial expression system. In this chapter, the prokaryotic expression and the subsequent purification of VLP of betanodavirus orange-spotted grouper nervous necrosis virus (OGNNV) are presented. PMID:27076301

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

    PubMed

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

    1997-03-01

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

  12. Recent advances in biological production of 3-hydroxypropionic acid.

    PubMed

    Kumar, Vinod; Ashok, Somasundar; Park, Sunghoon

    2013-11-01

    3-Hydroxypropionic acid (3-HP) is a valuable platform chemical that can be produced biologically from glucose or glycerol. This review article provides an overview and the current status of microbial 3-HP production. The constraints of microbial 3-HP production and possible solutions are also described. Finally, future prospects of biological 3-HP production are discussed. PMID:23473969

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

    PubMed Central

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

    2013-01-01

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

  14. Biological treatment of shrimp production wastewater.

    PubMed

    Boopathy, Raj

    2009-07-01

    Over the last few decades, there has been an increase in consumer demand for shrimp, which has resulted in its worldwide aquaculture production. In the United States, the stringent enforcement of environmental regulations encourages shrimp farmers to develop new technologies, such as recirculating raceway systems. This is a zero-water exchange system capable of producing high-density shrimp yields. The system also produces wastewater characterized by high levels of ammonia, nitrate, nitrite, and organic carbon, which make waste management costs prohibitive. Shrimp farmers have a great need for a waste management method that is effective and economical. One such method is the sequencing batch reactor (SBR). A SBR is a variation of the activated sludge biological treatment process. This process uses multiple steps in the same reactor to take the place of multiple reactors in a conventional treatment system. The SBR accomplishes equalization, aeration, and clarification in a timed sequence in a single reactor system. This is achieved through reactor operation in sequences, which includes fill, react, settle, decant, and idle. A laboratory scale SBR was successfully operated using shrimp aquaculture wastewater. The wastewater contained high concentrations of carbon and nitrogen. By operating the reactors sequentially, namely, aerobic and anoxic modes, nitrification and denitrification were achieved as well as removal of carbon. Ammonia in the waste was nitrified within 4 days. The denitrification of nitrate was achieved by the anoxic process, and 100% removal of nitrate was observed within 15 days of reactor operation. PMID:19396482

  15. Two initial vaccinations with the Bm86-based Gavacplus vaccine against Rhipicephalus (Boophilus) microplus induce similar reproductive suppression to three initial vaccinations under production conditions

    PubMed Central

    2010-01-01

    Background The cattle tick, Rhipicephalus (Boophilus) microplus, affects livestock production in many regions of the world. Up to now, the widespread use of chemical acaricides has led to the selection of acaricide-resistant ticks and to environmental contamination. Gavacplus is a subunit vaccine based on the recombinant Bm86 tick antigen expressed in yeast, capable to control infestations of R. microplus under controlled and production conditions. The vaccine constitutes the core element of broad control programs against this ectoparasite, in which acquired immunity in cattle to Bm86 is combined with a rational use of acaricides. At present, the conventional vaccine scheme consists of three doses that should be administered at weeks 0, 4 and 7, followed by a booster every six months. Results In this study we assayed a reduction in the number of the initial doses of Gavacplus, evaluated the time course and the level of bovine anti-Bm86 antibodies elicited, and analyzed the vaccine effect on ticks engorging on immunized cattle under production conditions. Following three different immunization schemes, the bovines developed a strong and specific immune response characterized by elevated anti-Bm86 IgG titers. A reduction in the weight of engorging female ticks, in the weight of the eggs laid and also in R. microplus viable eggs percentage was obtained by using only two doses of Gavacplus administered at weeks 0 and 4, followed by a booster six months later. This reduction did not differ from the results obtained on ticks engorging on cattle immunized at weeks 0, 4 and 7. It was also demonstrated that anti-Bm86 antibody titers over 1:640, measured in bovines immunized at weeks 0 and 4, were sufficient to affect weight and reproductive potential of female ticks as compared with ticks engorging on unvaccinated animals. In addition, no statistically significant differences were detected in the average weight of eggs laid by ticks engorged on immunized cattle that showed

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

    PubMed

    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

  17. 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

  18. Biological and phylogenetic characterization of a genotype VII Newcastle disease virus from Venezuela: efficacy of field vaccination.

    PubMed

    Perozo, Francisco; Marcano, Rosmar; Afonso, Claudio L

    2012-04-01

    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

  19. 77 FR 28883 - Cooperative Agreement To Support Innovation in Vaccine Clinical Trial Design and Collaboration in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ..., regulatory control, and surveillance of vaccines and biological medicinal products are major challenges for... and unmet need exists. Diseases such as malaria, tuberculosis, and human immunodeficiency virus...

  20. Experimental production of clinical-grade dendritic cell vaccine for acute myeloid leukemia.

    PubMed

    Tan, Yuen-Fen; Sim, Geok-Choo; Habsah, Aziz; Leong, Chooi-Fun; Cheong, Soon-Keng

    2008-12-01

    Dendritic cells (DC) are professional antigen presenting cells of the immune system. Through the use of DC vaccines (DC after exposure to tumour antigens), cryopreserved in single-use aliquots, an attractive and novel immunotherapeutic strategy is available as an option for treatment. In this paper we describe an in vitro attempt to scale-up production of clinical-grade DC vaccines from leukemic cells. Blast cells of two relapsed AML patients were harvested for DC generation in serum-free culture medium containing clinical-grade cytokines GM-CSF, IL-4 and TNF-alpha. Cells from patient 1 were cultured in a bag and those from patient 2 were cultured in a flask. The numbers of seeding cells were 2.24 x 10(8) and 0.8 x 10(8), respectively. DC yields were 10 x 10(6) and 29.8 x 10(6) cells, giving a conversion rate of 4.7% and 37%, respectively. These DC vaccines were then cryopreserved in approximately one million cells per vial with 20% fresh frozen group AB plasma and 10% DMSO. At 12 months and 21 months post cryopreservation, these DC vaccines were thawed, and their sterility, viability, phenotype and functionality were studied. DC vaccines remained sterile up to 21 months of storage. Viability of the cryopreserved DC in the culture bag and flask was found to be 50% and 70% at 12 months post cryopreservation respectively; and 48% and 67% at 21 months post cryopreservation respectively. These DC vaccines exhibited mature DC surface phenotypic markers of CD83, CD86 and HLA-DR, and negative for haemopoietic markers. Mixed lymphocyte reaction (MLR) study showed functional DC vaccines. These experiments demonstrated that it is possible to produce clinical-grade DC vaccines in vitro from blast cells of leukemic patients, which could be cryopreserved up to 21 months for use if repeated vaccinations are required in the course of therapy. PMID:19291915

  1. Estimated economic benefits during the 'decade of vaccines' include treatment savings, gains in labor productivity.

    PubMed

    Stack, Meghan L; Ozawa, Sachiko; Bishai, David M; Mirelman, Andrew; Tam, Yvonne; Niessen, Louis; Walker, Damian G; Levine, Orin S

    2011-06-01

    In 2010 the Bill & Melinda Gates Foundation announced a $10 billion commitment over the next ten years to increase access to childhood vaccines in the world's poorest countries. The effort was labeled the "Decade of Vaccines." This study estimates both the short- and long-term economic benefits from the introduction and increased use of six vaccines in seventy-two of the world's poorest countries from 2011 to 2020. Increased rates of vaccination against pneumococcal and Haemophilus influenzae type b pneumonia and meningitis, rotavirus, pertussis, measles, and malaria over the next ten years would save 6.4 million lives and avert 426 million cases of illness, $6.2 billion in treatment costs, and $145 billion in productivity losses. Monetary estimates based on this type of analysis can be used to determine the return on investment in immunization from both the international community and local governments, and they should be considered in policy making. PMID:21653952

  2. A Plant-Based Transient Expression System for the Rapid Production of Malaria Vaccine Candidates.

    PubMed

    Boes, Alexander; Reimann, Andreas; Twyman, Richard M; Fischer, Rainer; Schillberg, Stefan; Spiegel, Holger

    2016-01-01

    There are currently no vaccines that provide sterile immunity against malaria. Various proteins from different stages of the Plasmodium falciparum life cycle have been evaluated as vaccine candidates, but none of them have fulfilled expectations. Therefore, combinations of key antigens from different stages of the parasites life cycle may be essential for the development of efficacious malaria vaccines. Following the identification of promising antigens using bioinformatics, proteomics, and/or immunological approaches, it is necessary to express, purify, and characterize these proteins and explore the potential of fusion constructs combining different antigens or antigen domains before committing to expensive and time-consuming clinical development. Here, using malaria vaccine candidates as an example, we describe how Agrobacterium tumefaciens-based transient expression in plants can be combined with a modular and flexible cloning strategy as a robust and versatile tool for the rapid production of candidate antigens during research and development. PMID:27076325

  3. 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. PMID:27389971

  4. No adverse effects of simultaneous vaccination with the immunocontraceptive GonaCon and a commercial rabies vaccine on rabies virus neutralizing antibody production in dogs.

    PubMed

    Bender, Scott C; Bergman, David L; Wenning, Krista M; Miller, Lowell A; Slate, Dennis; Jackson, Felix R; Rupprecht, Charles E

    2009-11-27

    Parenteral vaccination campaigns are integral to the elimination of canine rabies. To maximize herd immunity in dogs, immunocontraception provided at the time of rabies vaccination should reduce fecundity and dog abundance. GonaCon has been used successfully as an immunocontraceptive in a variety of mammals, and by inference, the dog would be an ideal candidate for testing. As an initial step in evaluating a combination-vaccination program, we assessed the effects of GonaCon on rabies virus neutralizing antibody production in dogs after administration of a veterinary rabies vaccine. Eighteen feral/free ranging dogs were included in this initial study: six were given GonaCon only, six were given rabies vaccination only, and six received GonaCon and rabies vaccination. Antibody levels were evaluated over 82 days. The use of the immunocontraceptive GonaCon did not affect the ability of dogs to seroconvert in response to the rabies vaccine. Thus, GonaCon provides a potential immunocontraceptive for use in combination with rabies vaccine to increase herd immunity and address dog population over abundance to better manage rabies. PMID:19925955

  5. 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. PMID:27039212

  6. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  7. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Biological products and related terms. 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... shall be considered a serial of the multiple fraction product. (i) Subserial. Each of two or...

  8. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products and related terms. 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... shall be considered a serial of the multiple fraction product. (i) Subserial. Each of two or...

  9. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... products. 103.3 Section 103.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.3 Shipment of... Animal and Plant Health Inspection Service. (f) Data acceptable to the Administrator demonstrating...

  10. Vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antigens that are processed by antigen-processing cells via the exogenous pathway elicit antibodies. Thus, extracellular bacteria (live or killed), inactivated viral particles, portions (subunits) of virus, and products are processed by the exogenous pathway. Epitopes are presented to the immune sys...

  11. Development of Mycoplasma hyopneumoniae Recombinant Vaccines.

    PubMed

    Marchioro, Silvana Beutinger; Simionatto, Simone; Dellagostin, Odir

    2016-01-01

    Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), a disease that affects swine production worldwide. Vaccination is the most cost-effective strategy for the control and prevention of the disease. Research using genome-based approach has the potential to elucidate the biology and pathogenesis of M. hyopneumoniae and contribute to the development of more effective vaccines. Here, we describe the protocol for developing M. hyopneumoniae recombinant vaccines using reverse vaccinology approaches. PMID:27076288

  12. 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. PMID:24235227

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

    PubMed Central

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

    2013-01-01

    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. PMID:26344340

  14. 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

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

    PubMed

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

    2014-10-21

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  17. Cholesterol oxidation products and their biological importance.

    PubMed

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr; Rog, Tomasz; Vattulainen, Ilpo

    2016-09-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have a substantial effect on membrane properties. In this spirit, this review describes the biological importance and the roles of oxysterols in the human body. We focus primarily on the effect of oxysterols on lipid membranes, but we also consider other issues such as enzymatic and nonenzymatic synthesis processes of oxysterols as well as pathological conditions induced by oxysterols. PMID:26956952

  18. A plant‐based system for rapid production of influenza vaccine antigens

    PubMed Central

    Shoji, Yoko; Farrance, Christine E.; Bautista, James; Bi, Hong; Musiychuk, Konstantin; Horsey, April; Park, HeeWoo; Jaje, Jennifer; Green, Brian J.; Shamloul, Moneim; Sharma, Satish; Chichester, Jessica A.; Mett, Vadim; Yusibov, Vidadi

    2011-01-01

    Please cite this paper as: Shoji et al. (2011) A plant‐based system for rapid production of influenza vaccine antigens. Influenza and Other Respiratory Viruses 6(3), 204–210. Background  Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is to manufacture and administer pandemic vaccines in sufficient quantities and to do so in a timely manner without impacting the regular seasonal influenza vaccine capacity. Current, egg‐based, influenza vaccine production is well established and provides an effective product, but has limited capacity and speed. Objectives  To satisfy the additional global demand for emerging influenza vaccines, high‐performance cost‐effective technologies need to be developed. Plants have a potential as an economic and efficient large‐scale production platform for vaccine antigens. Methods  In this study, a plant virus‐based transient expression system was used to produce hemagglutinin (HA) proteins from the three vaccine strains used during the 2008–2009 influenza season, A/Brisbane/59/07 (H1N1), A/Brisbane/10/07 (H3N2), and B/Florida/4/06, as well as from the recently emerged novel H1N1 influenza A virus, A/California/04/09. Results  The recombinant plant‐based HA proteins were engineered and produced in Nicotiana benthamiana plants within 2 months of obtaining the genetic sequences specific to each virus strain. These antigens expressed at the rate of 400–1300 mg/kg of fresh leaf tissue, with >70% solubility. Immunization of mice with these HA antigens induced serum anti‐HA IgG and hemagglutination inhibition antibody responses at the levels considered protective against these virus infections. Conclusions  These results demonstrate the feasibility of our transient plant

  19. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 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...

  20. 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...

  1. 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...

  2. Keynote symposium - avian influenza: Vectors, vaccines, public health, and product marketability introduction and welcome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper is the introduction to the Keynote Symposium titled “Avian Influenza: Vectors, Vaccines, Public Health, and Product Marketability” that the author organized for the Poultry Science Association (PSA) on July 20, 2008. The purpose of the symposium was to provide the members and guests of PS...

  3. [Development of new vaccines].

    PubMed

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

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

  4. Study designs for the nonclinical safety testing of new vaccine products.

    PubMed

    Forster, Roy

    2012-07-01

    During the development of a new vaccine, the purpose of nonclinical studies is to provide safety information to support the clinical development and licensure of the product. In this article the study designs currently accepted for the nonclinical safety testing of new vaccines are described for single dose, local tolerance, repeat dose toxicity and safety pharmacology studies; these studies together form the basis of a typical nonclinical safety evaluation dossier. The detailed design of the preclinical package must take account of the intended clinical use, patient population, route of administration, formulation, dose level and immunisation schedule. The test item that is used for these studies must be adequately representative of the intended clinical formulation. The animal model used for these studies must be selected on criteria of relevance. Single dose toxicity studies provide information on acute actions or the potential effect of accidental overdose, but this information is often available from the repeat dose toxicity study, obviating the need for the acute study. Local tolerance studies provide information on tissue reactions at the site of administration. Evaluation of the findings must distinguish between normal tissue responses to injected material and findings indicative of undesirable pathological changes. The repeated dose toxicity studies are the principal studies that support the safety profile of the vaccines. The design of these studies must take full account of the features of the vaccine in the choice of treatment regime, dose levels, pharmacodynamic monitoring and timing of investigations and sacrifice. Safety pharmacology studies are performed to evaluate the potential for undesirable secondary pharmacological actions of vaccines if there is data to suggest that such studies are needed; this evaluation is made on a case by case basis. In the absence of specific guidance the design of studies for therapeutic vaccines follows the same

  5. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

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

  6. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

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

  7. Biological Activity of Recently Discovered Halogenated Marine Natural Products

    PubMed Central

    Gribble, Gordon W.

    2015-01-01

    This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included. PMID:26133553

  8. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1991-01-01

    Previously studies have shown the importance of both medium composition and concentration and medium pH on ethanol production of Clostridium ljungdahlii in fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas. Four additional batch experiments involving medium composition and concentration were carried out in modified basal medium without yeast extract at pH 4.0. These experiments indicate that basal medium with only small amounts of B-vitamins can yield significant cell growth while yielding ethanol as the major product. Product ratios as high as 11.0 g ethanol per g acetate were obtained with half strength B-vitamins. Further experiments indicates that Ca-pantothenate may be necessary for the growth of C. ljungdahlii and that growth and ethanol production can occur simultaneously.

  9. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-01-01

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

  10. Biological production of ethanol fom coal

    SciTech Connect

    Not Available

    1992-05-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  13. Systems biological approaches to measure and understand vaccine immunity in humans

    PubMed Central

    Li, Shuzhao; Nakaya, Helder I; Kazmin, Dmitri A; Oh, Jason; Pulendran, Bali

    2013-01-01

    Recent studies have demonstrated the utility of using systems approaches to identify molecular signatures that can be used to predict vaccine immunity in humans. Such approaches are now being used extensively in vaccinology, and are beginning to yield novel insights about the molecular networks driving vaccine immunity. In this review, we present a broad review of the methodologies involved in these studies, and discuss the promise and challenges involved in this emerging field of “systems vaccinology.” PMID:23796714

  14. 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

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

    PubMed Central

    2012-01-01

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

  16. The potential of plants as a system for the development and production of human biologics

    PubMed Central

    Chen, Qiang; Davis, Keith R.

    2016-01-01

    The growing promise of plant-made biologics is highlighted by the success story of ZMapp™ as a potentially life-saving drug during the Ebola outbreak of 2014-2016. Current plant expression platforms offer features beyond the traditional advantages of low cost, high scalability, increased safety, and eukaryotic protein modification. Novel transient expression vectors have been developed that allow the production of vaccines and therapeutics at unprecedented speed to control potential pandemics or bioterrorism attacks. Plant-host engineering provides a method for producing proteins with unique and uniform mammalian post-translational modifications, providing opportunities to develop biologics with increased efficacy relative to their mammalian cell-produced counterparts. Recent demonstrations that plant-made proteins can function as biocontrol agents of foodborne pathogens further exemplify the potential utility of plant-based protein production. However, resolving the technical and regulatory challenges of commercial-scale production, garnering acceptance from large pharmaceutical companies, and obtaining U.S. Food and Drug Administration approval for several major classes of biologics are essential steps to fulfilling the untapped potential of this technology. PMID:27274814

  17. The potential of plants as a system for the development and production of human biologics.

    PubMed

    Chen, Qiang; Davis, Keith R

    2016-01-01

    The growing promise of plant-made biologics is highlighted by the success story of ZMapp™ as a potentially life-saving drug during the Ebola outbreak of 2014-2016. Current plant expression platforms offer features beyond the traditional advantages of low cost, high scalability, increased safety, and eukaryotic protein modification. Novel transient expression vectors have been developed that allow the production of vaccines and therapeutics at unprecedented speed to control potential pandemics or bioterrorism attacks. Plant-host engineering provides a method for producing proteins with unique and uniform mammalian post-translational modifications, providing opportunities to develop biologics with increased efficacy relative to their mammalian cell-produced counterparts. Recent demonstrations that plant-made proteins can function as biocontrol agents of foodborne pathogens further exemplify the potential utility of plant-based protein production. However, resolving the technical and regulatory challenges of commercial-scale production, garnering acceptance from large pharmaceutical companies, and obtaining U.S. Food and Drug Administration approval for several major classes of biologics are essential steps to fulfilling the untapped potential of this technology. PMID:27274814

  18. Biological production of liquid fuels from biomass

    SciTech Connect

    1982-01-01

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

  19. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-05-01

    Research is continuing in attempting to increase both the ethanol concentration and product ratio (acetate to ethanol) from the C. ljungdahlii fermentation. Both batch and continuous reactors are being used for this purpose. The purpose of this report is four-fold. First, the data presented in PETC Report No. 2-4-91 (June--September, 1991) are analyzed and interpreted using normalized specific growth and production rates. This technique eliminates experimental variation due to differences in inoculum history. Secondly, the effects of the sulfur gases H{sub 2}S and COS on the performance of C. ljungdahlii are presented and discussed. Although these are preliminary results, they illustrate the tolerance of the bacterium to low levels of sulfur gases. Thirdly, the results of continuous stirred tank reactor studies are presented, where cell and product concentrations are shown as a function of agitation rate and gas flow rate. Finally, additional data are presented showing the performance of C. ljungdahlii in a CSTR with cell recycle.

  20. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1991-01-01

    Research is continuing in attempting to increase both the ethanol concentration and product ratio from the C. ljungdahlii fermentation. Both batch and continuous reactors are being used for this purpose. The purpose of this report is four-fold. First, the data presented in PETC Report No. 2-4-91 (June--September 1991) are analyzed and interpreted using normalized specific growth and production rates. This technique eliminates experimental variation due to the differences in inoculum history. Secondly, the effects of the sulfur gases H{sub 2}S and COS on the performance of C. ljungdahlii are presented and discussed. Although these are preliminary results, they illustrate the tolerance of the bacterium to low levels of sulfur gases. Thirdly, the results of continuous stirred tank reactor studies are presented, where cell and product concentrations are shown as a function of agitation rate and gas flow rate. Finally, additional data are presented showing the performance of C. ljungdahlii in a CSTR with cell recycle.

  1. Neurotrophic Natural Products: Chemistry and Biology

    PubMed Central

    Xu, Jing; Lacoske, Michelle H.

    2014-01-01

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

  2. 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. PMID:15491873

  3. Changing climate increases biological productivity in the Arctic

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2011-11-01

    Climate change is leading to increased biological productivity in the coastal Arctic. As ice melts and recedes far from land, winds interact with open waters to increase the upwelling of nutrient-rich deep water and stimulate biological productivity. Tremblay et al. quantified these changes using remote sensing and in situ observations in the coastal Beaufort Sea. They found that ice ablation and the combination of increased upwelling and greater light penetration into the water column during fall 2007 and summer 2008 increased the production of ice algae, phytoplankton, and zooplankton by 2-6 times. (Geophysical Research Letters, doi:10.1029/2011GL048825, 2011)

  4. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... for production of biologics. 113.51 Section 113.51 Animals and Animal Products ANIMAL AND PLANT HEALTH... production of biologics. Primary cells used to prepare biological products shall be derived from normal... of Production, each batch of primary cells used to prepare a biological product shall be tested...

  5. History of vaccination

    PubMed Central

    Plotkin, Stanley

    2014-01-01

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

  6. Antiradiation UV Vaccine: UV Radiation, Biological effects, lesions and medical management - immune-therapy and immune-protection.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    rabbits, 11-12 months old, live weight 3.5-3.7 (n=11), Balb mice, 2-3 months old, live weight 20-22 g (n=33), Wistar rats, 3-4 months old, live weight 180-220 g(n=33). The studies were approved by the Animal Care and Use Committee for ethical animal research equivalent, at each institution. Seven rabbits, ten mice, eleven Wistar rats were vaccinated with a UV antiradiation vaccine. A second group of animals was used as biological control which received vaccine but no UV Radiation and a third group of animals was used as control without any interventions. Before and after UV Radiation, Vaccination with the UV antiradiation vaccine were provided 17 days prior to UV exposure. The animals were irradiated by a DRT-1 UV generator lamp. The dose of irradiation for laboratory, experimental animals was 10-12 * Standard Erythema Dose (SED) at L=283,7 Laboratory animals were placed in to the box with ventilation. Results: Ultraviolet irradiation of the skin was performed with high doses and causes an inflammation or erythema in all experimental animals. However the grade of skin damage and inflammation was significantly different between animals protected by vaccination and non-protected, non-vaccinated animals. Animals UV-irradiated, but who did not receive the antiradiation vaccine suffered from extensive UV skin burns of second or third degree (grade 2-3). However, animals protected with the UV antiradiation vaccine demonstrated much mild forms of skin cellular injury - mainly erythema, first degree skin burns and a few small patches with second degree skin burns (grade 1-2). Discussion: The severity of skin damage depended on area of exposed skin, time and dose of UV irradiation. Skin injury could be divided into 4 major grades: 1. Faint erythema with dry desquamation. 2. Moderate to severe erythema. 3. Severe erythema with blistering, moist desquamation. 4. Toxic epidermal necrolysis. Mild doses of UV radiation and ionizing radiation can induce cell death by apoptosis and

  7. Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies

    PubMed Central

    Sasaki, Sanae; Sullivan, Meghan; Narvaez, Carlos F.; Holmes, Tyson H.; Furman, David; Zheng, Nai-Ying; Nishtala, Madhuri; Wrammert, Jens; Smith, Kenneth; James, Judith A.; Dekker, Cornelia L.; Davis, Mark M.; Wilson, Patrick C.; Greenberg, Harry B.; He, Xiao-Song

    2011-01-01

    During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies. PMID:21785218

  8. Production of a Shigella sonnei Vaccine Based on Generalized Modules for Membrane Antigens (GMMA), 1790GAHB

    PubMed Central

    Gerke, Christiane; Colucci, Anna Maria; Giannelli, Carlo; Sanzone, Silvia; Vitali, Claudia Giorgina; Sollai, Luigi; Rossi, Omar; Martin, Laura B.; Auerbach, Jochen; Di Cioccio, Vito; Saul, Allan

    2015-01-01

    Recently, we developed a high yield production process for outer membrane particles from genetically modified bacteria, called Generalized Modules of Membrane Antigens (GMMA), and the corresponding simple two step filtration purification, enabling economic manufacture of these particles for use as vaccines. Using a Shigella sonnei strain that was genetically modified to produce penta-acylated lipopolysaccharide (LPS) with reduced endotoxicity and to maintain the virulence plasmid encoding for the immunodominant O antigen component of the LPS, scale up of the process to GMP pilot scale was straightforward and gave high yields of GMMA with required purity and consistent results. GMMA were formulated with Alhydrogel and were highly immunogenic in mice and rabbits. In mice, a single immunization containing 29 ng protein and 1.75 ng of O antigen elicited substantial anti-LPS antibody levels. As GMMA contain LPS and lipoproteins, assessing potential reactogenicity was a key aspect of vaccine development. In an in vitro monocyte activation test, GMMA from the production strain showed a 600-fold lower stimulatory activity than GMMA with unmodified LPS. Two in vivo tests confirmed the low potential for reactogenicity. We established a modified rabbit pyrogenicity test based on the European Pharmacopoeia pyrogens method but using intramuscular administration of the full human dose (100 μg of protein). The vaccine elicited an average temperature rise of 0.5°C within four hours after administration, which was considered acceptable and showed that the test is able to detect a pyrogenic response. Furthermore, a repeat dose toxicology study in rabbits using intramuscular (100 μg/dose), intranasal (80 μg/dose), and intradermal (10 μg/dose) administration routes showed good tolerability of the vaccine by all routes and supported its suitability for use in humans. The S. sonnei GMMA vaccine is now in Phase 1 dose-escalation clinical trials. PMID:26248044

  9. The Interstellar Production of Biologically Important Organics

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  10. Optimizing selection of large animals for antibody production by screening immune response to standard vaccines.

    PubMed

    Thompson, Mary K; Fridy, Peter C; Keegan, Sarah; Chait, Brian T; Fenyö, David; Rout, Michael P

    2016-03-01

    Antibodies made in large animals are integral to many biomedical research endeavors. Domesticated herd animals like goats, sheep, donkeys, horses and camelids all offer distinct advantages in antibody production. However, their cost of use is often prohibitive, especially where poor antigen response is commonplace; choosing a non-responsive animal can set a research program back or even prevent experiments from moving forward entirely. Over the course of production of antibodies from llamas, we found that some animals consistently produced a higher humoral antibody response than others, even to highly divergent antigens, as well as to their standard vaccines. Based on our initial data, we propose that these "high level responders" could be pre-selected by checking antibody titers against common vaccines given to domestic farm animals. Thus, time and money can be saved by reducing the chances of getting poor responding animals and minimizing the use of superfluous animals. PMID:26775851

  11. The potential of Physcomitrella patens as a platform for the production of plant-based vaccines.

    PubMed

    Rosales-Mendoza, Sergio; Orellana-Escobedo, Lucía; Romero-Maldonado, Andrea; Decker, Eva L; Reski, Ralf

    2014-02-01

    The moss Physcomitrella patens has a number of advantages for the production of biopharmaceuticals, including: i) availability of standardized conditions for cultivation in bioreactors; ii) not being part of the food chain; iii) high biosafety; iv) availability of highly efficient transformation methods; v) a haploid, fully sequenced genome providing genetic stability and uniform expression; vi) efficient gene targeting at the nuclear level allows for the generation of mutants with specific post-translational modifications (e.g., glycosylation patterns); and vii) oral formulations are a viable approach as no toxic effects are attributed to ingestion of this moss. In the light of this panorama, this opinion paper analyzes the possibilities of using P. patens for the production of oral vaccines and presents some specific cases where its use may represent significant progress in the field of plant-based vaccine development. The advantages represented by putative adjuvant effects of endogenous secondary metabolites and producing specific glycosylation patterns are highlighted. PMID:24405402

  12. Vaccination and acute phase mediator production in chickens challenged with low pathogenic avian influenza virus; novel markers for vaccine efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods to determine vaccine efficacy of low pathogenic avian influenza (LPAI) isolates are limited in poultry because experimental infections with LPAI virus in specific pathogen free chickens rarely causes clinical disease. The most commonly used method to compare LPAI vaccine efficacy is to quant...

  13. Light-enhanced primary marine aerosol production from biologically productive seawater

    NASA Astrophysics Data System (ADS)

    Long, M. S.; Keene, W. C.; Kieber, D. J.; Frossard, A. A.; Russell, L. M.; Maben, J. R.; Kinsey, J. D.; Quinn, P. K.; Bates, T. S.

    2014-04-01

    Physical and biogeochemical processes in seawater controlling primary marine aerosol (PMA) production and composition are poorly understood and associated with large uncertainties in estimated fluxes into the atmosphere. PMA production was investigated in the biologically productive NE Pacific Ocean and in biologically productive and oligotrophic regions of the NW Atlantic Ocean. Physicochemical properties of model PMA, produced by aeration of fresh seawater under controlled conditions, were quantified. Diel variability in model PMA mass and number fluxes was observed in biologically productive waters, increasing following sunrise and decreasing to predawn levels overnight. Such variability was not seen in oligotrophic waters. During daytime, surfactant scavenging by aeration in the aerosol generator without replenishing the seawater in the reservoir reduced the model PMA production in productive waters to nighttime levels but had no influence on production from oligotrophic waters. Results suggest bubble plume interactions with sunlight-mediated biogenic surfactants in productive seawater significantly enhanced model PMA production.

  14. Milk kefir: composition, microbial cultures, biological activities, and related products

    PubMed Central

    Prado, Maria R.; Blandón, Lina Marcela; Vandenberghe, Luciana P. S.; Rodrigues, Cristine; Castro, Guillermo R.; Thomaz-Soccol, Vanete; Soccol, Carlos R.

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance. PMID:26579086

  15. Assessment of biological Hydrogen production processes: A review

    NASA Astrophysics Data System (ADS)

    Najafpour, G. D.; Shahavi, M. H.; Neshat, S. A.

    2016-06-01

    Energy crisis created a special attention on renewable energy sources. Among these sources; hydrogen through biological processes is well-known as the most suitable and renewable energy sources. In terms of process yield, hydrogen production from various sources was evaluated. A summary of microorganisms as potential hydrogen producers discussed along with advantages and disadvantages of several bioprocesses. The pathway of photo-synthetic and dark fermentative organisms was discussed. In fact, the active enzymes involved in performance of biological processes for hydrogen generation were identified and their special functionalities were discussed. The influential factors affecting on hydrogen production were known as enzymes assisting liberation specific enzymes such as nitrogenase, hydrogenase and uptake hydrogenase. These enzymes were quite effective in reduction of proton and form active molecular hydrogen. Several types of photosynthetic systems were evaluated with intension of maximum hydrogen productivities. In addition dark fermentative and light intensities on hydrogen productions were evaluated. The hydrogen productivities of efficient hydrogen producing strains were evaluated.

  16. 75 FR 75682 - Reclassification of Category IIIA Biological Products, Bacterial Vaccines and Related Biological...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... order finalizes the proposed order published in the Federal Register of May 15, 2000 (65 FR 31003) (May..., 1973 (38 FR 4319), FDA issued procedures for the review by independent advisory panels of the safety... codified in Sec. 601.25 (21 CFR 601.25) (38 FR 32048 at 32052, November 20, 1973). Under Sec. 601.25,...

  17. Natural product synthesis at the interface of chemistry and biology

    PubMed Central

    2014-01-01

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880

  18. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

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

  19. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    MedlinePlus

    Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

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

    PubMed Central

    Singh, Shanteri; Phillips, George N.

    2012-01-01

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

  1. 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

  2. Pharmacist Substitution of Biological Products: Issues and Considerations.

    PubMed

    Li, Edward; Ramanan, Sundar; Green, Larry

    2015-07-01

    Biosimilars are biological products that are highly similar to their biological reference products, notwithstanding minor differences in clinically inactive components. However, unlike generics of small-molecule drugs, biosimilars are not identical to their reference products, since each manufacturer uses unique cell lines and processes, and these lead to slight structural differences between products. Because these structural variations can lead to differences in clinical response, clinical studies demonstrating biosimilarity are required before and robust pharmacovigilance after approval. Although the FDA has not yet issued formal guidance on interchangeable biosimilars, higher standards of similarity will be required in order to achieve an interchangeable designation. In this commentary, we review the differences between generics and biosimilars, describe their respective regulatory approval pathways, discuss interchangeability and substitution, and review substitution of interchangeable biosimilars, focusing on key professional considerations for pharmacists. PMID:26108377

  3. 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

  4. Continuous downstream processing for high value biological products: A Review.

    PubMed

    Zydney, Andrew L

    2016-03-01

    There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. PMID:26153056

  5. Oral vaccination of dogs with recombinant rabies virus vaccines.

    PubMed

    Rupprecht, Charles E; Hanlon, Cathleen A; Blanton, Jesse; Manangan, Jamie; Morrill, Patricia; Murphy, Staci; Niezgoda, Michael; Orciari, Lillian A; Schumacher, Carolin L; Dietzschold, Bernhard

    2005-07-01

    Oral rabies virus (RV) vaccines are used to immunize a diversity of mammalian carnivores, but no single biological is effective for all major species. Recently, advances in reverse genetics have allowed the design of recombinant RV for consideration as new vaccines. The objective of this experiment was to examine the safety, immunogenicity and efficacy of recombinant RV vaccines administered to captive dogs by the oral route, compared to a commercial vaccinia-rabies glycoprotein (V-RG) recombinant virus vaccine. Animals consisted of naive purpose-bred beagles of both sexes, and were 6 months of age or older. Dogs were randomly assigned to one of six groups, and received either diluent or vaccine (PBS; V-RG; RV SN10-333; RV SPBN-Cyto c; RV SPBNGA; RV SPBNGAGA), with at least six animals per group. On day 0, 1 ml of each vaccine (or PBS) was administered to the oral cavity of each dog, at an approximate concentration of 10(8) to 10(9) TCID50. After vaccination, dogs were observed daily and bled weekly, for 5 weeks, prior to RV challenge. No signs of illness related to vaccination were detected during the observation period. Excluding the controls, RV neutralizing antibodies were detected in the majority of animals within 1-2 weeks of primary vaccination. Thereafter, all dogs were inoculated in the masseter muscle with a street virus of canine origin. All control animals developed rabies, but no vaccinates succumbed, with the exception of a single dog in the V-RG group. Review of these preliminary data demonstrates the non-inferiority of recombinant RV products, as concerns both safety and efficacy, and supports the suggestion that these vaccines may hold promise for future development as oral immunogens for important carnivore species, such as dogs. PMID:15896409

  6. Biological cleaning of soil and reservoirs from oil products

    SciTech Connect

    Zinberg, M.B.; Ivanovskaya, I.B.; Gafarov, N.A.

    1996-12-31

    The production of oil and gas condensate invariably involves environmental hazards: water and soil contamination due to miscellaneous breakdowns of technological equipment and pipeline damage. Among many existing contamination methods biological cleaning has become more popular lately. It took us some years to make investigations and to carry out a number of field tests in order to develop biological methods of cleaning soil and reservoirs from oil and gas condensate products. Our method is based on the use of special biological agents containing various active hydrocarbon oxidizing bacteria. It has been experimentally proved that biological agents of {open_quotes}Devouroil{close_quotes} possess the greatest oxidizing properties. {open_quotes}Devouroil{close_quotes} contains five kinds of hydrocarbon oxidizing bacteria of Pseudomonas, Rodococcus, Candida genera. These bacteria are extracted from natural ecosystems: underground waters, soils, reservoirs. As the agents are grown on oil distillate, they are very destructive to different oil products. We also proved the described microorganisms ability to oxidize sulfate oil and hydrocarbon condensate, which are the most toxic components. For four years our colleagues have been cleaning soil and reservoirs contaminated with oil, black oil, gas condensate and other products of hydrocarbon origin. This method was used to treat different kinds of soil and ground (grass and arable land, swamp and forest) in actual hazardous situations involving oil and gas condensate spills. Besides it was successfully applied to clean sludge storage which had been filled with oil process sewage for several years.

  7. PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    EPA Science Inventory

    PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    Miroslav Styblo1,2,*, Zuzana Drobna1, Felecia S. Walton1, Ilona Jaspers1,2, Shan Lin3,
    Stephen B. Waters3, David J. Thomas4

    1Department of Pediatrics, 2Center for Environmental Medicine an...

  8. Natural products with health benefits from marine biological resources

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. Biology and management of psocids infesting stored products

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) For biological products regulated by the Center for Biologics Evaluation and Research (CBER), send the.../biodev.htm. (2) For biological products regulated by the Center for Drug Evaluation and Research...

  11. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) For biological products regulated by the Center for Biologics Evaluation and Research (CBER), send the.../biodev.htm. (2) For biological products regulated by the Center for Drug Evaluation and Research...

  12. 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. PMID:23863285

  13. Pilot-scale production and characterization of paramyosin, a vaccine candidate for schistosomiasis japonica.

    PubMed

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

    2008-07-01

    Despite effective chemotherapy, schistosomiasis remains a major public health problem in the developing world, with at least 200 million active infections resulting in significant morbidity. Rapid reinfection after treatment, accompanied by extensive residual morbidity, mandates alternative control strategies, including vaccine development. Paramyosin, a myofibrillar protein found only in invertebrates, has been widely studied as a vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum. Recently, we demonstrated that Th2-biased immune responses to paramyosin are associated with resistance to reinfection with S. japonicum in humans; however, challenges in the pilot-scale production of schistosome paramyosin have hampered further studies of this promising vaccine candidate. Here we report a method for the pilot-scale expression and purification of recombinant S. japonicum paramyosin (rSj97). rSj97 was extracted from Escherichia coli inclusion bodies and purified with sequential anion-exchange, hydroxyapatite, and size exclusion chromatography. The purified rSj97 was >95% pure as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis and was free of significant endotoxin contamination. We demonstrate that, like native paramyosin, rSj97 adopts an alpha-helical coiled-coil tertiary structure and binds immunoglobulin and collagen. Naïve mice infected with S. japonicum produce anti-rSj97 immunoglobulin G (IgG) antibodies as early as 4 weeks postinfection, while sera collected from S. japonicum-infected individuals contain anti-rSj97 IgE antibodies. Our method for pilot-scale production of recombinant full-length paramyosin will facilitate preclinical evaluation of paramyosin as a vaccine for schistosomiasis. PMID:18426875

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

    PubMed

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

    2015-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was conducted to determine the impact of vaccination with Vectormune®FP MG on egg production and egg quality characteristics of white leghorn hens. Due to questions of the efficacy of this vaccine in preventing M. gallisepticum mediated pathology, the ability of this vaccine to protect a...

  16. Selecting Viruses for the Seasonal Influenza Vaccine

    MedlinePlus

    ... which viruses are selected for use in vaccine production? The influenza viruses in the seasonal flu vaccine ... to get a good vaccine virus for vaccine production? There are a number of factors that can ...

  17. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.2 Disposition of animals administered experimental biological products...

  18. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.2 Disposition of animals administered experimental biological products...

  19. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.2 Disposition of animals administered experimental biological products...

  20. 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

  1. 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

  2. Microbial Production of Isoprenoids Enabled by Synthetic Biology

    PubMed Central

    Immethun, Cheryl M.; Hoynes-O’Connor, Allison G.; Balassy, Andrea; Moon, Tae Seok

    2013-01-01

    Microorganisms transform inexpensive carbon sources into highly functionalized compounds without toxic by-product generation or significant energy consumption. By redesigning the natural biosynthetic pathways in an industrially suited host, microbial cell factories can produce complex compounds for a variety of industries. Isoprenoids include many medically important compounds such as antioxidants and anticancer and antimalarial drugs, all of which have been produced microbially. While a biosynthetic pathway could be simply transferred to the production host, the titers would become economically feasible when it is rationally designed, built, and optimized through synthetic biology tools. These tools have been implemented by a number of research groups, with new tools pledging further improvements in yields and expansion to new medically relevant compounds. This review focuses on the microbial production of isoprenoids for the health industry and the advancements though synthetic biology. PMID:23577007

  3. Effect of different culture systems on the production of foot and mouth disease trivalent vaccine

    PubMed Central

    Hassan, Amr Ismail

    2016-01-01

    Aim: This study aims to determine the effect of the stationary rawx, roller, and the suspension cell culture systems on the total virus yield infectivity and antigenicity. Materials and Methods: Three serotypes of foot and mouth disease virus (FMDV) (serotype A, O and SAT-2) were inoculated separately into baby hamster kidney-21 cell line in rawx, roller, and suspension cultivation systems using multiplicity of infection (1:100). Samples were taken from the total virus yield from each system at 15, 18, 21, and 24 h post-inoculation. Testing the total virus yield infectivity through virus titration and antigenicity through estimation of complement fixing titer and 146S content and evaluation of the potency of the vaccine prepared from the different cultivation systems were done. Results: The results showed that the FMDV titer of serotype A, O, and SAT-2 obtained from the roller cultivation system showed the highest level followed by suspension cultivation system then the rawx cultivation system. The FMDV titer showed its highest level at 21 h post-inoculation in all the cultivation systems and then decline at 24 h post-inoculation. The antigenicity reached its highest value content at 18 h post-inoculation either by complement fixation test or by quantifying the 146S intact virion. Montanide ISA 206 oil inactivated trivalent vaccines were prepared from the tested serotypes (A Iran O5. O Panasia and SAT-2/EGY/2012) harvested at 18 h post-inoculation from the 3 culture systems. The results of tracing the antibody response showed that the mean antibody response from the roller cultivation system start its protective antibody titer earlier at 2 weeks post-vaccination (WPV) than the vaccine prepared from the other two cultivation system and the immune protection period lasts longer for 36 WPV for the roller cultivation system vaccine than the other two cultivation systems. Conclusion: The best cultivation system used for the production of FMD vaccine regarding its

  4. 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

  5. Hepatitis Vaccines.

    PubMed

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

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

  6. Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care.

    PubMed

    Perez-Pinera, Pablo; Han, Ningren; Cleto, Sara; Cao, Jicong; Purcell, Oliver; Shah, Kartik A; Lee, Kevin; Ram, Rajeev; Lu, Timothy K

    2016-01-01

    Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care. PMID:27470089

  7. Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care

    PubMed Central

    Perez-Pinera, Pablo; Han, Ningren; Cleto, Sara; Cao, Jicong; Purcell, Oliver; Shah, Kartik A.; Lee, Kevin; Ram, Rajeev; Lu, Timothy K.

    2016-01-01

    Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care. PMID:27470089

  8. A Model to Explain How the Bacille Calmette Guérin (BCG) Vaccine Drives Interleukin-12 Production in Neonates

    PubMed Central

    Kativhu, Chido Loveness; Libraty, Daniel H.

    2016-01-01

    The Bacille Calmette Guérin (BCG) vaccine is the only routine vaccination at birth that effectively induces neonatal T-helper 1 (Th1)-polarized immune responses. The primary cytokine that drives CD4+ T-cell Th1 differentiation is interleukin (IL)-12 p70, a heterodimeric cytokine composed of the IL-12 p35 and IL-12 p40 subunits. We therefore examined the mechanisms involved in BCG vaccine stimulation of IL-12 p35 and p40 production from human umbilical cord (neonatal) cells. We found that BCG bacilli did not upregulate IL-12 p35 mRNA production, but upregulated IL-12 p40 mRNA production in a Toll-like receptor (TLR)2-dependent manner, in human neonatal monocyte-derived dendritic cells (mdDCs). The combination of TLR2 signaling, Type I interferon (IFN), and Type II IFN induced maximal levels of IL-12 p35 and p40 mRNA production in human neonatal mdDCs. The cell-free supernatants of reconstituted BCG vaccine vials contained extracellular mycobacterial (BCG) DNA which could induce IFN-α (Type I IFN) production in human neonatal plasmacytoid dendritic cells (pDCs). BCG bacilli also stimulated human neonatal CD16lo natural killer (NK) cells to produce IFN-γ (Type II IFN) in a TLR2-dependent manner. We have therefore proposed a model where BCG vaccine could stimulate the combination of neonatal conventional DCs (cDCs), pDCs, and CD16lo NK cells to produce optimal neonatal IL-12 p35 and p40 (IL-12 p70) production and subsequent CD4+ T-cell Th1 polarization. An adjuvant that emulates the mechanism by which the BCG vaccine stimulates neonatal IL-12 p35 and p40 production could improve vaccine strategies at birth for protection against intracellular pathogens and toxins. PMID:27571272

  9. A Model to Explain How the Bacille Calmette Guérin (BCG) Vaccine Drives Interleukin-12 Production in Neonates.

    PubMed

    Kativhu, Chido Loveness; Libraty, Daniel H

    2016-01-01

    The Bacille Calmette Guérin (BCG) vaccine is the only routine vaccination at birth that effectively induces neonatal T-helper 1 (Th1)-polarized immune responses. The primary cytokine that drives CD4+ T-cell Th1 differentiation is interleukin (IL)-12 p70, a heterodimeric cytokine composed of the IL-12 p35 and IL-12 p40 subunits. We therefore examined the mechanisms involved in BCG vaccine stimulation of IL-12 p35 and p40 production from human umbilical cord (neonatal) cells. We found that BCG bacilli did not upregulate IL-12 p35 mRNA production, but upregulated IL-12 p40 mRNA production in a Toll-like receptor (TLR)2-dependent manner, in human neonatal monocyte-derived dendritic cells (mdDCs). The combination of TLR2 signaling, Type I interferon (IFN), and Type II IFN induced maximal levels of IL-12 p35 and p40 mRNA production in human neonatal mdDCs. The cell-free supernatants of reconstituted BCG vaccine vials contained extracellular mycobacterial (BCG) DNA which could induce IFN-α (Type I IFN) production in human neonatal plasmacytoid dendritic cells (pDCs). BCG bacilli also stimulated human neonatal CD16lo natural killer (NK) cells to produce IFN-γ (Type II IFN) in a TLR2-dependent manner. We have therefore proposed a model where BCG vaccine could stimulate the combination of neonatal conventional DCs (cDCs), pDCs, and CD16lo NK cells to produce optimal neonatal IL-12 p35 and p40 (IL-12 p70) production and subsequent CD4+ T-cell Th1 polarization. An adjuvant that emulates the mechanism by which the BCG vaccine stimulates neonatal IL-12 p35 and p40 production could improve vaccine strategies at birth for protection against intracellular pathogens and toxins. PMID:27571272

  10. Vaccination of chickens against coccidiosis ameliorates drug resistance in commercial poultry production

    PubMed Central

    Chapman, H. David; Jeffers, Thomas K.

    2014-01-01

    Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been documented for all the dozen or so drugs approved for use in chickens and varying levels of resistance is present for those currently employed. A possible solution may be the introduction of drug-sensitive parasites into the houses where poultry are raised so that they may replace such drug-resistant organisms. This can be achieved by utilizing live vaccines that contain strains of Eimeria that were isolated before most anticoccidial compounds were introduced. Such strains are inherently drug-sensitive. Practical proposals to achieve this objective involve the alternation of vaccination with medication (known as rotation programs) in successive flocks reared in the same poultry house. A proposal for a yearly broiler production cycle involving chemotherapy and vaccination is presented. There are few, if any, examples in veterinary parasitology where it has proved possible to restore sensitivity to drugs used to control a widespread parasite. Further research is necessary to ascertain whether this can result in sustainable and long-term control of Eimeria infections in poultry. PMID:25516830

  11. Vaccination of chickens against coccidiosis ameliorates drug resistance in commercial poultry production.

    PubMed

    Chapman, H David; Jeffers, Thomas K

    2014-12-01

    Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been documented for all the dozen or so drugs approved for use in chickens and varying levels of resistance is present for those currently employed. A possible solution may be the introduction of drug-sensitive parasites into the houses where poultry are raised so that they may replace such drug-resistant organisms. This can be achieved by utilizing live vaccines that contain strains of Eimeria that were isolated before most anticoccidial compounds were introduced. Such strains are inherently drug-sensitive. Practical proposals to achieve this objective involve the alternation of vaccination with medication (known as rotation programs) in successive flocks reared in the same poultry house. A proposal for a yearly broiler production cycle involving chemotherapy and vaccination is presented. There are few, if any, examples in veterinary parasitology where it has proved possible to restore sensitivity to drugs used to control a widespread parasite. Further research is necessary to ascertain whether this can result in sustainable and long-term control of Eimeria infections in poultry. PMID:25516830

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

    PubMed

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

    2000-03-01

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

  13. 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 ...

  14. Optimization of the Production of Inactivated Clostridium novyi Type B Vaccine Using Computational Intelligence Techniques.

    PubMed

    Aquino, P L M; Fonseca, F S; Mozzer, O D; Giordano, R C; Sousa, R

    2016-07-01

    Clostridium novyi causes necrotic hepatitis in sheep and cattle, as well as gas gangrene. The microorganism is strictly anaerobic, fastidious, and difficult to cultivate in industrial scale. C. novyi type B produces alpha and beta toxins, with the alpha toxin being linked to the presence of specific bacteriophages. The main strategy to combat diseases caused by C. novyi is vaccination, employing vaccines produced with toxoids or with toxoids and bacterins. In order to identify culture medium components and concentrations that maximized cell density and alpha toxin production, a neuro-fuzzy algorithm was applied to predict the yields of the fermentation process for production of C. novyi type B, within a global search procedure using the simulated annealing technique. Maximizing cell density and toxin production is a multi-objective optimization problem and could be treated by a Pareto approach. Nevertheless, the approach chosen here was a step-by-step one. The optimum values obtained with this approach were validated in laboratory scale, and the results were used to reload the data matrix for re-parameterization of the neuro-fuzzy model, which was implemented for a final optimization step with regards to the alpha toxin productivity. With this methodology, a threefold increase of alpha toxin could be achieved. PMID:27003282

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

    PubMed

    Genzel, Yvonne

    2015-05-01

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

  16. 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. PMID:20537553

  17. Systems Biology of Recombinant Protein Production in Bacillus megaterium

    NASA Astrophysics Data System (ADS)

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

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

  18. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

    PubMed Central

    Crane, Erika A.

    2016-01-01

    Abstract Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products. PMID:26833854

  19. Antiradiation UV Vaccine: UV Radiation, Biological effects, lesions and medical management - immune-therapy and immune-protection.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    rabbits, 11-12 months old, live weight 3.5-3.7 (n=11), Balb mice, 2-3 months old, live weight 20-22 g (n=33), Wistar rats, 3-4 months old, live weight 180-220 g(n=33). The studies were approved by the Animal Care and Use Committee for ethical animal research equivalent, at each institution. Seven rabbits, ten mice, eleven Wistar rats were vaccinated with a UV antiradiation vaccine. A second group of animals was used as biological control which received vaccine but no UV Radiation and a third group of animals was used as control without any interventions. Before and after UV Radiation, Vaccination with the UV antiradiation vaccine were provided 17 days prior to UV exposure. The animals were irradiated by a DRT-1 UV generator lamp. The dose of irradiation for laboratory, experimental animals was 10-12 * Standard Erythema Dose (SED) at L=283,7 Laboratory animals were placed in to the box with ventilation. Results: Ultraviolet irradiation of the skin was performed with high doses and causes an inflammation or erythema in all experimental animals. However the grade of skin damage and inflammation was significantly different between animals protected by vaccination and non-protected, non-vaccinated animals. Animals UV-irradiated, but who did not receive the antiradiation vaccine suffered from extensive UV skin burns of second or third degree (grade 2-3). However, animals protected with the UV antiradiation vaccine demonstrated much mild forms of skin cellular injury - mainly erythema, first degree skin burns and a few small patches with second degree skin burns (grade 1-2). Discussion: The severity of skin damage depended on area of exposed skin, time and dose of UV irradiation. Skin injury could be divided into 4 major grades: 1. Faint erythema with dry desquamation. 2. Moderate to severe erythema. 3. Severe erythema with blistering, moist desquamation. 4. Toxic epidermal necrolysis. Mild doses of UV radiation and ionizing radiation can induce cell death by apoptosis and

  20. Theoretical and methodological aspects of BCG vaccine from the discovery of Calmette and Guérin to molecular biology. A review.

    PubMed

    Lugosi, L

    1992-10-01

    The BCG vaccine has been used to prevent tuberculosis since 1921 and applied for immunostimulation in neoplasia since the 1960s. Both the preventive and immunostimulation effects have been evaluated and communicated with contradictory, positive and negative conclusions. For an objective evaluation and interpretation of the protective efficacy, effectiveness and efficiency of the BCG vaccination it must be considered that: (1) several BCG substrains have been developed in manufacturing laboratories that differ in the residual virulence which determines immunogenicity and reactogenicity; (2) various liquid and freeze-dried BCG vaccine production methods are used, resulting in different BCG viable units per dose; (3) quantitative bioassay methods are not yet being used for statistical quality control of the vaccine; (4) BCG products are applied in various demographical, epidemiological and socioeconomic conditions with different vaccination policies; (5) inadequate biostatistical models are often used to analyse efficacy, effectiveness and adverse reactions. The same conditions influence the precise evaluation of BCG immunostimulation in neoplasia. Recombinant DNA technology will modify production methods, and explain at the molecular level the mechanism of the protective effects BCG confers in tuberculosis and immunostimulation in neoplasia. High level laboratory techniques and biostatistical methods, based on probability logic and inductive inference, ensure appropriate experimental designs and the exact analysis of laboratory data and the results of vaccination policies. They will lead to the evaluation of the protective effect of BCG in order to reduce the BCG contradictions. PMID:1493232

  1. The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems.

    PubMed

    Kirkpatrick, Beth D; Colgate, E Ross; Mychaleckyj, Josyf C; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Nayak, Uma; Taniuchi, Mami; Naylor, Caitlin; Qadri, Firdausi; Ma, Jennie Z; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Petri, William A

    2015-04-01

    Oral vaccines appear less effective in children in the developing world. Proposed biologic reasons include concurrent enteric infections, malnutrition, breast milk interference, and environmental enteropathy (EE). Rigorous study design and careful data management are essential to begin to understand this complex problem while assuring research subject safety. Herein, we describe the methodology and lessons learned in the PROVIDE study (Dhaka, Bangladesh). A randomized clinical trial platform evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of EE and additional exploratory variables. Methods for the enrollment and 2-year follow-up of a 700 child birth cohort are described, including core laboratory, safety, regulatory, and data management practices. Intense efforts to standardize clinical, laboratory, and data management procedures in a developing world setting provide clinical trials rigor to all outcomes. Although this study infrastructure requires extensive time and effort, it allows optimized safety and confidence in the validity of data gathered in complex, developing country settings. PMID:25711607

  2. United States vaccine research: a delicate fabric of public and private collaboration. National Vaccine Advisory Committee.

    PubMed

    1997-12-01

    In the last 20 years, two thirds of all new vaccines provided worldwide have been produced by a US network of independent industrial, governmental, and academic partners engaged in vaccine research and development. Vaccines are complex products and the science of vaccinology is difficult. To achieve the full promise of modern science and technology to prevent and treat disease by immunization, the delicate fabric of America's cooperative and collaborative vaccine research relationships must be sustained and strengthened. The major partners are the federal government; four large companies--two US-headquartered (Wyeth-Lederle Biologics and Vaccines and Merck & Co), two foreign firms (SmithKline Beecham and Pasteur Mérieux Connaught); and academia. Of the $1.4 billion that fund US vaccine research and development annually, 46% comes from vaccine sales, 36% from taxpayers, and 18% from risk capital. Vaccine innovation could be strengthened by improved public and policy maker understanding of the vaccine development network; declarations of partnership; interactive dialog with federal advisory bodies; public forums for government and industry to listen to patients, providers and researchers; sabbatical assignments between partners; mechanisms to share industries' market research with public immunization programs; continued active industry participation in the Advisory committee on Immunization Practices and the National Vaccine Advisory committee; increased collaboration between industry and the National Institutes of Health for clinical research; harmonization of the Advisory Committee on Immunization Practices vaccine recommendations and the Food and Drug Administration package inserts; and public policies to foster the partnership's collaboration and robustness. The optimal size and configuration of the US vaccine enterprise should be debated only in the context of a full understanding of how the current system works and its record of effectiveness. These National

  3. Systems Biology Approaches to Understand Natural Products Biosynthesis

    PubMed Central

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K.; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete’s biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets. PMID:26697425

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

    PubMed Central

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

    2012-01-01

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

  5. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Reporting of biological product deviations by... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Establishment Standards § 600.14 Reporting of biological product deviations by licensed manufacturers. (a) Who must report...

  6. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Reporting of biological product deviations by... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Establishment Standards § 600.14 Reporting of biological product deviations by licensed manufacturers. (a) Who must report...

  7. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Reporting of biological product deviations by... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Establishment Standards § 600.14 Reporting of biological product deviations by licensed manufacturers. (a) Who must report...

  8. 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. PMID:26814192

  9. Formate Formation and Formate Conversion in Biological Fuels Production

    PubMed Central

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

    2011-01-01

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

  10. From population to public institutions: what needs to be changed to benefit from the full value of vaccination

    PubMed Central

    Szucs, Thomas; Quilici, Sibilia; Panfilo, Marina

    2015-01-01

    The poor perception of the benefits of vaccines, and their subsequent underuse, can result in substantial economic, societal, and political burden. Adequate support and communication from health authorities and governments is essential to promote the benefits of vaccination and reduce the risk of infectious diseases outbreaks. Cost-containment policies in the vaccine procurement processes could also be a threat to the long-term sustainability of the vaccine industry and manufacturing sites in Europe. Biologicals, such as vaccines, are highly technical and complex products to manufacture and only a few industries are engaged in this activity. Developing incentives to encourage vaccine manufacturers and identifying means of taking into consideration the specificities of vaccines in economic evaluations could allow the full value of vaccination to be appreciated. In conclusion, governments, international agencies, and other stakeholders have an important role to play to help society regain confidence in vaccination and ensure that the benefits of vaccination programmes are fully recognised and valued. PMID:27123169

  11. Evaluation of cell substrates for the production of biologicals: Revision of WHO recommendations. Report of the WHO Study Group on Cell Substrates for the Production of Biologicals, 22-23 April 2009, Bethesda, USA.

    PubMed

    Knezevic, I; Stacey, G; Petricciani, J; Sheets, R

    2010-01-01

    Evaluating cell substrates for producing vaccines and other biologicals is one of the critical aspects in assuring quality and safety of these products. As part of its mission in setting standards for biological products, WHO provides recommendations for manufacturing and evaluating biologicals. Regular updates of the guidance documents are important to manufacturers and regulators worldwide. WHO Expert Committee on Biological Standardization (ECBS) identified a need for revising the requirements for cell substrates (WHO TRS 878, annex 1). In response, WHO established a Study Group (SG) in 2006 that prepared an updated set of recommendations for using cell substrates for the production of biologicals. A summary of the proposed changes that the SG made in 2007 is available at WHO web site (http://www.who.int/biologicals/publications/meetings/areas/vaccines/cells/en/index.html). Draft revised recommendations were circulated to regulators, manufacturers and other experts for comments in April 2009. The SG held its third meeting on 22-23 April 2009 to review progress in the revision and to propose further improvements. In addition, the experts discussed the need for reference preparations, reference cell banks, and standardization of testing methodologies. The SG proposed clarifications of the rationale for in vivo testing as well as the potential for applying new methods for in vitro testing for detecting microbial agents. In line with this, WHO should conduct review of the current manufacturers' practice in using tests for microbial agents and interpreting these results. Additionally, WHO should take a lead in developing an International Standard for nucleic acid amplification test (NAT) for detecting mycoplasma contamination in cell substrates. WHO Collaborating Centers will lead this initiative, involving other relevant institutions in this area. Finally, advice on the replacement of the WHO Vero reference cell bank 10-87 with respect to the source of cells and re

  12. 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. PMID:14677694

  13. A Cucumber Mosaic Virus Based Expression System for the Production of Porcine Circovirus Specific Vaccines

    PubMed Central

    Gellért, Ákos; Salánki, Katalin; Tombácz, Kata; Tuboly, Tamás; Balázs, Ervin

    2012-01-01

    Potential porcine circovirus type 2 (PCV2) capsid protein epitopes, suitable for expression on the surface of cucumber mosaic virus (CMV) particles were determined by a thorough analysis of the predicted PCV capsid protein structure. The ab initio protein structure prediction was carried out with fold recognition and threading methods. The putative PCV epitopes were selected on the basis of PCV virion models and integrated into the plant virus coat protein, after amino acid position 131. The recombinants were tested for infectivity and stability on different Nicotiana species and stable recombinant virus particles were purified. The particles were tested for their ability to bind to PCV induced porcine antibodies and used for specific antibody induction in mice and pigs. The results showed that PCV epitopes expressed on the CMV surface were recognized by the porcine antibodies and they were also able to induce PCV specific antibody response. Challenge experiment with PCV2 carried out in immunized pigs showed partial protection against the infection. Based on these results it was concluded that specific antiviral vaccine production for the given pathogen was feasible, offering an inexpensive way for the mass production of such vaccines. PMID:23285149

  14. A cucumber mosaic virus based expression system for the production of porcine circovirus specific vaccines.

    PubMed

    Gellért, Akos; Salánki, Katalin; Tombácz, Kata; Tuboly, Tamás; Balázs, Ervin

    2012-01-01

    Potential porcine circovirus type 2 (PCV2) capsid protein epitopes, suitable for expression on the surface of cucumber mosaic virus (CMV) particles were determined by a thorough analysis of the predicted PCV capsid protein structure. The ab initio protein structure prediction was carried out with fold recognition and threading methods. The putative PCV epitopes were selected on the basis of PCV virion models and integrated into the plant virus coat protein, after amino acid position 131. The recombinants were tested for infectivity and stability on different Nicotiana species and stable recombinant virus particles were purified. The particles were tested for their ability to bind to PCV induced porcine antibodies and used for specific antibody induction in mice and pigs. The results showed that PCV epitopes expressed on the CMV surface were recognized by the porcine antibodies and they were also able to induce PCV specific antibody response. Challenge experiment with PCV2 carried out in immunized pigs showed partial protection against the infection. Based on these results it was concluded that specific antiviral vaccine production for the given pathogen was feasible, offering an inexpensive way for the mass production of such vaccines. PMID:23285149

  15. Intensification of tropical Pacific biological productivity due to volcanic eruptions

    NASA Astrophysics Data System (ADS)

    Chikamoto, Megumi O.; Timmermann, Axel; Yoshimori, Masakazu; Lehner, Flavio; Laurian, Audine; Abe-Ouchi, Ayako; Mouchet, Anne; Joos, Fortunat; Raible, Christoph C.; Cobb, Kim M.

    2016-02-01

    Major volcanic eruptions generate widespread ocean cooling, which reduces upper ocean stratification. This effect has the potential to increase nutrient delivery into the euphotic zone and boost biological productivity. Using externally forced last millennium simulations of three climate/Earth System models (Model for Interdisciplinary Research On Climate (MIROC), Community Earth System Model (CESM), and LOch-Vecode-Ecbilt-CLio-agIsm Model (LOVECLIM)), we test the hypothesis that large volcanic eruptions intensify nutrient-driven export production. It is found that strong volcanic radiative forcing enhances the likelihood of eastern Pacific El Niño-like warming in CESM and LOVECLIM. This leads to an initial reduction of nutrients and export production in the eastern equatorial Pacific. However, this initial response reverses after about 3 years in association with La Niña cooling. The resulting delayed enhancement of biological production resembles the multiyear response in MIROC. The model simulations show that volcanic impacts on tropical Pacific dynamics and biogeochemistry persist for several years, thus providing a new source for potential multiyear ecosystem predictability.

  16. The Late Miocene Carbon Isotope Shift and Marine Biological Productivity.

    NASA Astrophysics Data System (ADS)

    Diester-Haass, L.; Billups, K.; Emeis, K. C.

    2004-12-01

    The late Miocene global carbon isotope shift of approximately 1 per mil is not well understood. Is it linked to ocean-related processes such as the AƒAøAøâ_sA¬A.â_oBiologic BloomAƒAøAøâ_sA¬ \\(Farrell et al., 1995\\), or to changes in type \\(C3/C4 plants\\) or cover of terrestrial vegetation? Here we examine the evolution of marine biological productivity during the isotope shift at ODP Site 846 \\(Pacific equatorial upwelling, where the AƒAøAøâ_sA¬A.â_oBiologic BloomAƒAøAøâ_sA¬ has been first described, Farrell al, 1995\\) and at Indian Ocean Site 721 \\(monsoon-driven upwelling\\), and compare their productivity history with non upwelling locations in the Atlantic Ocean. The onset of the carbon isotope shift is accompanied at all locations by an increase in paleoproductivity derived from benthic foraminiferal accumulation rates \\(expressed as gC/cm2 * ky; Huerguera, 2000\\) and increased abundance of Uvigerina spp.. At the equatorial upwelling sites the increase is comparable to half present-day values to present-day values; in the Atlantic Ocean paleoproductivity increases from present-day up to 3 times present-day values. But the productivity maxima are not concurrent. The carbon isotope shift is accompanied by severe carbonate dissolution and reduced ventilation of bottom waters, as reflected in the occurrence of pyrite and good preservation of cartilageous fish debris. Carbonate preservation is good since about 6 Ma despite high productivity. We discuss changing deep water circulation patterns, increased weathering and continental nutrient delivery, as well as erosion of terrestrial vegetation as possible factors to explain our findings.

  17. Vaccines in Dermatology

    PubMed Central

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

    2015-01-01

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

  18. Mechanism of Action for Anti-Radiation Vaccine in Reducing the Biological Impact of High-Dose Irradiation

    NASA Technical Reports Server (NTRS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2006-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. We partially analyzed the biochemical characteristics of the SRDs. The SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  19. Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

    NASA Technical Reports Server (NTRS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2007-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  20. Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

    NASA Astrophysics Data System (ADS)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  1. Schistosomiasis vaccines

    PubMed Central

    Siddiqui, Bilal A.; Ganley-Leal, Lisa

    2011-01-01

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

  2. Molecular biology in studies of oceanic primary production

    SciTech Connect

    LaRoche, J.; Falkowski, P.G. ); Geider, R. . Coll. of Marine Studies)

    1992-01-01

    Remote sensing and the use of moored in situ instrumentation has greatly improved our ability to measure phytoplankton chlorophyll and photosynthesis on global scales with high temporal resolution. However, the interpretation of these measurements and their significance with respect to the biogeochemical cycling of carbon relies on their relationship with physiological and biochemical processes in phytoplankton. For example, the use of satellite images of surface chlorophyll to estimate primary production is often based on the functional relationship between photosynthesis and irradiance. A variety of environmental factors such as light, temperature, nutrient availability affect the photosynthesis/irradiance (P vs I) relationship in phytoplankton. We present three examples showing how molecular biology can be used to provide basic insight into the factors controlling primary productivity at three different levels of complexity: 1. Studies of light intensity regulation in unicellular alga show how molecular biology can help understand the processing of environmental cues leading to the regulation of photosynthetic gene expression. 2. Probing of the photosynthetic apparatus using molecular techniques can be used to test existing mechanistic models derived from the interpretation of physiological and biophysical measurements. 3. Exploratory work on the expression of specific proteins during nutrient-limited growth of phytoplankton may lead to the identification and production of molecular probes for field studies.

  3. Molecular biology in studies of oceanic primary production

    SciTech Connect

    LaRoche, J.; Falkowski, P.G.; Geider, R.

    1992-07-01

    Remote sensing and the use of moored in situ instrumentation has greatly improved our ability to measure phytoplankton chlorophyll and photosynthesis on global scales with high temporal resolution. However, the interpretation of these measurements and their significance with respect to the biogeochemical cycling of carbon relies on their relationship with physiological and biochemical processes in phytoplankton. For example, the use of satellite images of surface chlorophyll to estimate primary production is often based on the functional relationship between photosynthesis and irradiance. A variety of environmental factors such as light, temperature, nutrient availability affect the photosynthesis/irradiance (P vs I) relationship in phytoplankton. We present three examples showing how molecular biology can be used to provide basic insight into the factors controlling primary productivity at three different levels of complexity: 1. Studies of light intensity regulation in unicellular alga show how molecular biology can help understand the processing of environmental cues leading to the regulation of photosynthetic gene expression. 2. Probing of the photosynthetic apparatus using molecular techniques can be used to test existing mechanistic models derived from the interpretation of physiological and biophysical measurements. 3. Exploratory work on the expression of specific proteins during nutrient-limited growth of phytoplankton may lead to the identification and production of molecular probes for field studies.

  4. 21 CFR 610.53 - Dating periods for licensed biological products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Dating periods for licensed biological products. 610.53 Section 610.53 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS Dating Period Limitations § 610.53 Dating periods for licensed biological...

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

    PubMed Central

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

    2014-01-01

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

  6. Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects.

    PubMed

    Szczawinska-Poplonyk, Aleksandra; Breborowicz, Anna; Samara, Husam; Ossowska, Lidia; Dworacki, Grzegorz

    2015-08-01

    The impaired synthesis of antigen-specific antibodies, which is indispensable for an adaptive immune response to infections, is a fundamental pathomechanism that leads to clinical manifestations in children with antibody production defects. The aim of this study was to evaluate the synthesis of antigen-specific antibodies following immunization in relation to peripheral blood B cell subsets in young children with hypogammaglobulinemia. Twenty-two children, aged from 8 to 61 months, with a deficiency in one or more major immunoglobulin classes participated in the study. Postvaccination antibodies against tetanus and diphtheria toxoids, the surface antigen of the hepatitis B virus, and the capsular Haemophilus influenzae type b polysaccharide antigen were assessed along with an immunophenotypic evaluation of peripheral blood B lymph cell maturation. A deficiency of antibodies against the tetanus toxoid was assessed in 73% of cases and that against the diphtheria toxoid was assessed in 68% of cases, whereas a deficiency of antibodies against the surface antigen of the hepatitis B virus was revealed in 59% of the children included in the study. A defective response to immunization with a conjugate vaccine with the Haemophilus influenzae type b polysaccharide antigen was demonstrated in 55% of hypogammaglobulinemic patients. Increased proportions of transitional B lymph cells and an accumulation of plasmablasts accompanied antibody deficiencies. The defective response to vaccine protein and polysaccharide antigens is a predominating disorder of humoral immunity in children with hypogammaglobulinemia and may result from a dysfunctional state of the cellular elements of the immune system. PMID:26018535

  7. Natural products as a resource for biologically active compounds

    SciTech Connect

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod)/sub 3/ is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous /sup 13/C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the /sup 1/H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants.

  8. 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

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

    PubMed

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

    1992-07-01

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

  10. Current studies on physiological functions and biological production of lactosucrose.

    PubMed

    Mu, Wanmeng; Chen, Qiuming; Wang, Xiao; Zhang, Tao; Jiang, Bo

    2013-08-01

    Lactosucrose (O-β-D-galactopyranosyl-(1,4)-O-α-D-glucopyranosyl-(1,2)-β-D-fructofuranoside) is a trisaccharide formed from lactose and sucrose by enzymatic transglycosylation. This rare trisaccharide is a kind of indigestible carbohydrate, has good prebiotic effect, and promotes intestinal mineral absorption. It has been used as a functional ingredient in a range of food products which are approved as foods for specified health uses in Japan. Using lactose and sucrose as substrates, lactosucrose can be produced through transfructosylation by β-fructofuranosidase from Arthrobacter sp. K-1 or a range of levansucrases, or through transgalactosylation by β-galactosidase from Bacillus circulans. This article presented a review of recent studies on the physiological functions of lactosucrose and the biological production from lactose and sucrose by different enzymes. PMID:23828605

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

    PubMed

    Kubicek, Christian P

    2013-01-20

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

  12. 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

    2016-04-01

    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. PMID:26618392

  13. A multi-bioreactor system for optimal production of malaria vaccines with Pichia pastoris.

    PubMed

    Fricke, Jens; Pohlmann, Kristof; Tatge, Frithjof; Lang, Roman; Faber, Bart; Luttmann, Reiner

    2011-04-01

    The successful development of optimal multistage production processes for recombinant products with Pichia pastoris needs to meet three pre-conditions. These pre-conditions are (i) strategies for performing fully automated and observable processes, (ii) characterization of the host cell-specific reaction parameters in order to make an adapted process layout for feeding and aeration strategies, and (iii) knowledge of optimal operation parameter conditions for maximizing the expression productivity of target protein amount and/or quality. In this report, an approach of a fully automated multi-bioreactor plant is described that meets all these requirements. The expression and secretion of a potential malaria vaccine with Pichia pastoris was chosen as an example to demonstrate the quality of the bioreactor system. Methods for the simultaneous identification of reaction kinetics were developed for strain characterization. Process optimization was carried out by applying a sequential/parallel Design of Experiments. In the view of Process Analytical Technology (PAT)-applications and in order to develop fully automated and globally observable production processes, methods for quasi on-line monitoring of recombinant protein secretion titers and the immunological quality of the products are also discussed in detail. PMID:21472987

  14. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights... Calculation of patent term extension for a veterinary biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a veterinary biological product is eligible for extension, the...

  15. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  16. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., dangerous, or harmful biological products. 105.3 Section 105.3 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS SUSPENSION, REVOCATION, OR TERMINATION OF BIOLOGICAL LICENSES OR PERMITS § 105.3 Notices re: worthless, contaminated, dangerous, or harmful biological products. (a) If at any time...

  17. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights... Calculation of patent term extension for a veterinary biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a veterinary biological product is eligible for extension, the...

  18. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., dangerous, or harmful biological products. 105.3 Section 105.3 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS SUSPENSION, REVOCATION, OR TERMINATION OF BIOLOGICAL LICENSES OR PERMITS § 105.3 Notices re: worthless, contaminated, dangerous, or harmful biological products. (a) If at any time...

  19. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights... Calculation of patent term extension for a veterinary biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a veterinary biological product is eligible for extension, the...

  20. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., dangerous, or harmful biological products. 105.3 Section 105.3 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS SUSPENSION, REVOCATION, OR TERMINATION OF BIOLOGICAL LICENSES OR PERMITS § 105.3 Notices re: worthless, contaminated, dangerous, or harmful biological products. (a) If at any time...

  1. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  2. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights... Calculation of patent term extension for a veterinary biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a veterinary biological product is eligible for extension, the...

  3. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights... Calculation of patent term extension for a veterinary biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a veterinary biological product is eligible for extension, the...

  4. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  5. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  6. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  7. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., dangerous, or harmful biological products. 105.3 Section 105.3 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS SUSPENSION, REVOCATION, OR TERMINATION OF BIOLOGICAL LICENSES OR PERMITS § 105.3 Notices re: worthless, contaminated, dangerous, or harmful biological products. (a) If at any time...

  8. 75 FR 61497 - Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... revised definition of a ``biological product''; priorities for guidance development; scientific and... including a modification to the structure of the biological product) that results in a new indication, route... Biological Products; Public Hearing; Request for Comments AGENCY: Food and Drug Administration, HHS....

  9. 78 FR 19492 - Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-01

    ... during the development phase of a biosimilar biological product. This draft guidance describes the Agency... development and review of biosimilar biological products. \\1\\ See http://www.fda.gov/downloads/Drugs... between sponsors or applicants and FDA for biosimilar biological product development (BPD) programs. It...

  10. An overview of biological production of L-theanine.

    PubMed

    Mu, Wanmeng; Zhang, Tao; Jiang, Bo

    2015-01-01

    L-Theanine (γ-glutamylethylamide) is a unique non-protein amino acid that is naturally found in tea plants. It contributes to the umami taste and unique flavor to green tea infusion, and thus its content in tea leaves highly impacts the tea quality and price. In addition to the graceful taste, it has been proved to have many beneficial physiological effects, especially promoting relaxation and improving concentration and learning ability. Based on these promising advantages, L-theanine has been commercially developed as a valuable ingredient for use in food and beverages to improve and/or maintain human health. L-Theanine can be obtained by chemical synthesis or isolation from tea, while chemical synthesis of L-theanine is hard to be accepted by consumers and is not allowed to use in food industry, and isolation of L-theanine in high purity generally involves time-consuming, cost-ineffective, and complicated operational processes. Accordingly, the biological production of L-theanine has recently attracted much attention. Four kinds of bacterial enzymes, including L-glutamine synthetase, γ-glutamylmethylamide synthetase, γ-glutamyltranspeptidase, and L-glutaminase, have been characterized to have L-theanine-producing ability. Herein, an overview of recent studies on the biological production of L-theanine was presented. PMID:25871834

  11. Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold

    PubMed Central

    Henry, Kevin A.; Arbabi-Ghahroudi, Mehdi; Scott, Jamie K.

    2015-01-01

    For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use. PMID:26300850

  12. Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold.

    PubMed

    Henry, Kevin A; Arbabi-Ghahroudi, Mehdi; Scott, Jamie K

    2015-01-01

    For the past 25 years, phage display technology has been an invaluable tool for studies of protein-protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage's potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage's large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use. PMID:26300850

  13. Significant reduction in bacterial shedding and improvement in milk production in dairy farms after the use of a new inactivated paratuberculosis vaccine in a field trial

    PubMed Central

    2009-01-01

    Background Paratuberculosis vaccination has been in use in some regions for many decades, but results have not been widely spread. A new Mycobacterium avium subsp. paratuberculosis (MAP) killed vaccine was studied in relationship with its effects on fecal shedding and milk production in four farms while other two were kept as controls submitted to a test and cull scheme. Findings Fecal detection (n = 1829) and milking records (n = 2413) have been analyzed after two (5 herds) and four (1 herd) years of the beginning of the intervention. Shedder prevalence was reduced by 100% in three of the four vaccinated farms, 68% in the total of vaccinated animals and 46% in the two control farms. Total amount of MAP shed was reduced 77% in the vaccinated farms and 94% in the control farms. Overall milk production increased up to 3.9% after vaccination, while there was no significant difference in production after intervention in the non-vaccinated farms. Conclusion MAP shedding reduction can be quickly accomplished both by vaccination and by testing and culling. However, vaccination appears to be a less expensive and more sustainable strategy since it required one single intervention and was also associated with an increase in milk production. PMID:19930604

  14. Biological evaluation of nanosilver incorporated cellulose pulp for hygiene products.

    PubMed

    Kavitha Sankar, P C; Ramakrishnan, Reshmi; Rosemary, M J

    2016-04-01

    Cellulose pulp has a visible market share in personal hygiene products such as sanitary napkins and baby diapers. However it offers good surface for growth of microorganisms. Huge amount of research is going on in developing hygiene products that do not initiate microbial growth. The objective of the present work is to produce antibacterial cellulose pulp by depositing silver nanopowder on the cellulose fiber. The silver nanoparticles used were of less than 100 nm in size and were characterised using transmission electron microscopy and X-ray powder diffraction studies. Antibacterial activity of the functionalized cellulose pulp was proved by JIS L 1902 method. The in-vitro cytotoxicity, in-vivo vaginal irritation and intracutaneous reactivity studies were done with silver nanopowder incorporated cellulose pulp for introducing a new value added product to the market. Cytotoxicity evaluation suggested that the silver nanoparticle incorporated cellulose pulp is non-cytotoxic. No irritation and skin sensitization were identified in animals tested with specific extracts prepared from the test material in the in-vivo experiments. The results indicated that the silver nanopowder incorporated cellulose pulp meets the requirements of the standard practices recommended for evaluating the biological reactivity and has good biocompatibility, hence can be classified as a safe hygiene product. PMID:26838891

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

    PubMed

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

    2013-09-10

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

  16. Vaccination of channel catfish with extracellular products of Aeromonas hydrophila provides protection against infection by the pathogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aeromonas hydrophila, a Gram-negative bacterium, is one of the economically-important pathogens in modern aquaculture. Among various traits, extracellular products (ECP) secreted by the bacterium are considered to be essential factors for virulence. Whether vaccination with the ECP could produce imm...

  17. Egg production after virulent challenge is differentially affected by the genotype of Newcastle disease virus (NDV) vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poultry producers have reported that despite high antibody levels to Newcastle disease virus (NDV), a small decrease in egg production is observed when vaccinated birds are exposed to virulent NDV. While the decrease may be as low as 10%, when this is extended to millions of birds this economic los...

  18. Large scale production of a mammalian cell derived quadrivalent hepatitis C virus like particle vaccine.

    PubMed

    Earnest-Silveira, L; Christiansen, D; Herrmann, S; Ralph, S A; Das, S; Gowans, E J; Torresi, J

    2016-10-01

    A method for the large-scale production of a quadrivalent mammalian cell derived hepatitis C virus-like particles (HCV VLPs) is described. The HCV core E1 and E2 coding sequences of genotype 1a, 1b, 2a or 3a were co-expressed in Huh7 cell factories using a recombinant adenoviral expression system. The structural proteins self-assembled into VLPs that were purified from Huh7 cell lysates by iodixanol ultracentrifugation and Stirred cell ultrafiltration. Electron microscopy, revealed VLPs of the different genotypes that are morphologically similar. Our results show that it is possible to produce large quantities of individual HCV genotype VLPs with relative ease thus making this approach an alternative for the manufacture of a quadrivalent mammalian cell derived HCV VLP vaccine. PMID:27373602

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    The water present in waste streams from a human habitat must be recycled in Controlled Ecological Life Support Systems (CELSS) to limit resupply needs and attain self-sufficiency. Plants play an important role in providing food, regenerating air, and producing purified water via transpiration. However, we have shown that the surfactants present in hygiene waste water have acute toxic effects on plant growth (Bubenheim et al. 1994; Greene et al., 1994). These phytotoxic affects can be mitigated by allowing the microbial population on the root surface to degrade the surfactant, however, a significant suppression (several days) in crop performance is experienced prior to reaching sub-toxic surfactant levels and plant recovery. An effective alternative is to stabilize the microbial population responsible for degradation of the surfactant on an aerobic bioreactor and process the waste water prior to utilization in the hydroponic solution (Wisniewski and Bubenheim, 1993). A sensitive bioassay indicates that the surfactant phytotoxicity is suppressed by more than 90% within 5 hours of introduction of the gray water to the bioreactor; processing for more than 12 hours degrades more than 99% of the phytotoxin. Vapor Compression Distillation (VCD) is a physical / chemical method for water purification which employees sequential distillation steps to separate water from solids and to volatilize contaminants. The solids from the waste water are concentrated in a brine and the pure product water (70 - 90% of the total waste water volume depending on operating conditions) retains non of the phytotoxic effects. Results of the bioassay were used to guide evaluations of the suitability of recovered gray water following biological and VCD processing for hydroponic lettuce production in controlled environments. Lettuce crops were grown for 28 days with 100% of the input water supplied with recovered water from the biological processor or VCD. When compared with the growth of plants

  20. Hepatitis B Vaccine

    MedlinePlus

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  1. Hepatitis A Vaccine

    MedlinePlus

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis A?Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in ...

  2. Comparison of molecular and biological characteristics of a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine (ingelvac PRRS MLV), the parent strain of the vaccine (ATCC VR2332), ATCC VR2385, and two recent field isolates of PRRSV.

    PubMed

    Opriessnig, T; Halbur, P G; Yoon, K-J; Pogranichniy, R M; Harmon, K M; Evans, R; Key, K F; Pallares, F J; Thomas, P; Meng, X J

    2002-12-01

    The objectives of this study were to compare the molecular and biological characteristics of recent porcine reproductive and respiratory syndrome virus (PRRSV) field isolates to those of a modified live virus (MLV) PRRS vaccine and its parent strain. One hundred seventeen, 4-week-old pigs were randomly assigned to six groups. Group 1 (n = 20) served as sham-inoculated negative controls, group 2 (n = 19) was inoculated with Ingelvac PRRS MLV vaccine, group 3 (n = 20) was inoculated with the parent strain of the vaccine (ATCC VR2332), group 4 (n = 19) was inoculated with vaccine-like PRRSV field isolate 98-38803, group 5 (n = 19) was inoculated with PRRSV field isolate 98-37120, and group 6 (n = 20) was inoculated with known high-virulence PRRSV isolate ATCC VR2385. The levels of severity of gross lung lesions (0 to 100%) among the groups were significantly different at both 10 (P < 0.0001) and 28 days postinoculation (p.i.) (P = 0.002). At 10 days p.i., VR2332 (26.5% +/- 4.64%) and VR2385 (36.4% +/- 6.51%) induced gross lesions of significantly greater severity than 98-38803 (0.0% +/- 0.0%), 98-37120 (0.8% +/- 0.42%), Ingelvac PRRS MLV (0.9% +/- 0.46%), and negative controls (2.3% +/- 1.26%). At 28 days p.i., 98-37120 (17.2% +/- 6.51%) induced gross lesions of significantly greater severity than any of the other viruses. Analyses of the microscopic-interstitial-pneumonia-lesion scores (0 to 6) revealed that VR2332 (2.9 +/- 0.23) and VR2385 (3.1 +/- 0.35) induced significantly more severe lesions at 10 days p.i. At 28 days p.i., VR2385 (2.5 +/- 0.27), VR2332 (2.3 +/- 0.21), 98-38803 (2.6 +/- 0.29), and 98-37120 (3.0 +/- 0.41) induced significantly more severe lesions than Ingelvac PRRS MLV (0.7 +/- 0.17) and controls (0.7 +/- 0.15). The molecular analyses and biological characterizations suggest that the vaccine-like isolate 98-38803 (99.5% amino acid homology based on the ORF5 gene) induces microscopic pneumonia lesions similar in type to, but different in severity

  3. Domestic influenza vaccine production in Mexico: a state-owned and a multinational company working together for public health.

    PubMed

    Ponce-de-Leon, Samuel; Velazquez-Fernandez, Ruth; Bugarin-González, Jose; García-Bañuelos, Pedro; Lopez-Sotelo, Angelica; Jimenez-Corona, María-Eugenia; Padilla-Catalan, Francisco; Cervantes-Rosales, Rocio

    2011-07-01

    The Mexican Government developed a plan in 2004 for pandemic influenza preparedness that included local production of influenza vaccine. To achieve this, an agreement was concluded between Birmex - a state-owned vaccine manufacturer - and sanofi pasteur, a leading developer of vaccine technology. Under this agreement, sanofi pasteur will establish a facility in Mexico to produce antigen for up to 30 million doses of egg-based seasonal vaccine per year, and Birmex will build a facility to formulate, fill and package the inactivated split-virion influenza vaccine. As at November 2010, the sanofi pasteur facility has been completed and the Birmex plant is under construction. Most of the critical equipment has been purchased and is in the process of validation. In addition to intensive support from sanofi pasteur for the transfer of the technology, the project is supported by the Mexican Ministry of Health, complemented by Birmex's own budget and grants from the WHO developing country influenza technology transfer project. PMID:21684424

  4. Systems biology of recombinant protein production using Bacillus megaterium.

    PubMed

    Biedendieck, Rebekka; Borgmeier, Claudia; Bunk, Boyke; Stammen, Simon; Scherling, Christian; Meinhardt, Friedhelm; Wittmann, Christoph; Jahn, Dieter

    2011-01-01

    The Gram-negative bacterium Escherichia coli is the most widely used production host for recombinant proteins in both academia and industry. The Gram-positive bacterium Bacillus megaterium represents an increasingly used alternative for high yield intra- and extracellular protein synthesis. During the past two decades, multiple tools including gene expression plasmids and production strains have been developed. Introduction of free replicating and integrative plasmids into B. megaterium is possible via protoplasts transformation or transconjugation. Using His(6)- and StrepII affinity tags, the intra- or extracellular produced proteins can easily be purified in one-step procedures. Different gene expression systems based on the xylose controlled promoter P(xylA) and various phage RNA polymerase (T7, SP6, K1E) driven systems enable B. megaterium to produce up to 1.25g of recombinant protein per liter. Biomass concentrations of up to 80g/l can be achieved by high cell density cultivations in bioreactors. Gene knockouts and gene replacements in B. megaterium are possible via an optimized gene disruption system. For a safe application in industry, sporulation and protease-deficient as well as UV-sensitive mutants are available. With the help of the recently published B. megaterium genome sequence, it is possible to characterize bottle necks in the protein production process via systems biology approaches based on transcriptome, proteome, metabolome, and fluxome data. The bioinformatical platform (Megabac, http://www.megabac.tu-bs.de) integrates obtained theoretical and experimental data. PMID:21943898

  5. Biological production of ethanol from coal. Final report

    SciTech Connect

    Not Available

    1992-12-01

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

  6. Rotavirus vaccines.

    PubMed

    Barnes, G

    1998-01-01

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

  7. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested... determine that licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use. For purposes of reviewing biological products that have...

  8. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested... determine that licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use. For purposes of reviewing biological products that have...

  9. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested... determine that licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use. For purposes of reviewing biological products that have...

  10. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested... determine that licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use. For purposes of reviewing biological products that have...

  11. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested... determine that licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use. For purposes of reviewing biological products that have...

  12. Enhanced saccharification of biologically pretreated wheat straw for ethanol production.

    PubMed

    López-Abelairas, M; Lu-Chau, T A; Lema, J M

    2013-02-01

    The biological pretreatment of lignocellulosic biomass with white-rot fungi for the production of bioethanol is an alternative to the most used physico-chemical processes. After biological treatment, a solid composed of cellulose, hemicellulose, and lignin-this latter is with a composition lower than that found in the initial substrate-is obtained. On the contrary, after applying physico-chemical methods, most of the hemicellulose fraction is solubilized, while cellulose and lignin fractions remain in the solid. The optimization of the combination of cellulases and hemicellulases required to saccharify wheat straw pretreated with the white-rot fungus Irpex lacteus was carried out in this work. The application of the optimal dosage made possible the increase of the sugar yield from 33 to 54 %, and at the same time the reduction of the quantity of enzymatic mixture in 40 %, with respect to the initial dosage. The application of a pre-hydrolysis step with xylanases was also studied. PMID:23306886

  13. [Modalities of production and immunity conferred by an inactivated rabies vaccine originating from cell culture].

    PubMed

    Précausta, P; Soulebot, J P; Bugand, M; Brun, A; Chappuis, G

    1982-01-01

    Further to guidelines advised by the World Health Organization, an inactivated Rabies vaccine was prepared from virus propagated on cell culture. This vaccine is presented either in the freeze-dried form or in the liquid form together with an immunity adjuvant. The specific and nonspecific immunity of the vaccine is excellent. The potency, tested in laboratory animals and in species for which the vaccine is intended, satisfies recommendations published by the W.H.O. The immunity persistence, evaluated by the titration of serum antibodies and by challenge with a pathogenic virus, proves to be excellent 3 years following primovaccination. Finally, the stability of this vaccine is an interesting factor for its application, especially in the form of a combined vaccine. PMID:7128075

  14. Production and biological activities of yellow pigments from Monascus fungi.

    PubMed

    Chen, Gong; Wu, Zhenqiang

    2016-08-01

    Monascus yellow pigments (MYPs), are azaphilone compounds and one of the three main components of total Monascus pigments (MPs). Thirty-five hydrophilic or hydrophobic MYPs have been identified, with the majority being hydrophobic. Apart from screening special Monascus strains, some advanced approaches, such as extractive and high-cell-density fermentations, have been applied for developing or producing new MYPs, especially extracellular hydrophilic MYPs. The outstanding performance of MYPs in terms of resistance to photodegradation, as well as tolerance for temperature and pH, give natural MYPs reasonable prospects, compared with the orange and red MPs, for practical use in the present and future. Meanwhile, MYPs have shown promising potential for applications in the food and pharmaceutical industries based on their described bioactivities. This review briefly summarizes the reports to date on chemical structures, biological activities, biosynthetic pathways, production technologies, and physicochemical performances of MYPs. The existing problems for MYPs are discussed and research prospects proposed. PMID:27357404

  15. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Notices re: worthless, contaminated, dangerous, or harmful biological products. 105.3 Section 105.3 Animals and Animal Products ANIMAL AND PLANT... Notices re: worthless, contaminated, dangerous, or harmful biological products. (a) If at any time...

  16. 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...

  17. 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...

  18. 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...

  19. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... production of biologics. 113.52 Section 113.52 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Ingredient Requirements § 113.52 Requirements for cell lines used for production of biologics. When prescribed in an applicable Standard Requirement or in a filed Outline of Production...

  20. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Movement of detained biological... VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of detention. Except as provided in paragraphs (a) and (b) of this section, no biological...

  1. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Movement of detained biological... VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of detention. Except as provided in paragraphs (a) and (b) of this section, no biological...

  2. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Movement of detained biological... VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of detention. Except as provided in paragraphs (a) and (b) of this section, no biological...

  3. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Movement of detained biological... VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of detention. Except as provided in paragraphs (a) and (b) of this section, no biological...

  4. 9 CFR 118.3 - Movement of detained biological products; Termination of detention.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Movement of detained biological... VECTORS DETENTION; SEIZURE AND CONDEMNATION § 118.3 Movement of detained biological products; Termination of detention. Except as provided in paragraphs (a) and (b) of this section, no biological...

  5. Arthropod vaccines.

    PubMed

    Lee, R; Opdebeeck, J P

    1999-03-01

    Antigens located in the midgut of the tick are hidden from the host's immune system. Egg production of ticks can be reduced when ticks are fed on animals vaccinated with midgut antigens of the tick, and a subunit vaccine formulated with the recombinant antigen Bm86 is now available that can reduce the number of ticks infesting cattle grazing on pasture. Midgut antigens used in vaccines against insects that transmit pathogenic organisms to humans have not been as effective in reducing insect fecundity and an alternative approach may be necessary. Transmission-blocking vaccines directed at interfering with the vector-pathogen interaction could result in loss of vector competence and block the spread of disease-causing organisms. PMID:10198800

  6. Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood.

    PubMed

    Nakaya, Helder I; Clutterbuck, Elizabeth; Kazmin, Dmitri; Wang, Lili; Cortese, Mario; Bosinger, Steven E; Patel, Nirav B; Zak, Daniel E; Aderem, Alan; Dong, Tao; Del Giudice, Giuseppe; Rappuoli, Rino; Cerundolo, Vincenzo; Pollard, Andrew J; Pulendran, Bali; Siegrist, Claire-Anne

    2016-02-16

    The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4(+) T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses. PMID:26755593

  7. Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood

    PubMed Central

    Nakaya, Helder I.; Clutterbuck, Elizabeth; Kazmin, Dmitri; Wang, Lili; Cortese, Mario; Bosinger, Steven E.; Patel, Nirav B.; Zak, Daniel E.; Aderem, Alan; Dong, Tao; Del Giudice, Giuseppe; Rappuoli, Rino; Cerundolo, Vincenzo; Pollard, Andrew J.; Pulendran, Bali; Siegrist, Claire-Anne

    2016-01-01

    The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4+ T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses. PMID:26755593

  8. Hormones in international meat production: biological, sociological and consumer issues.

    PubMed

    Galbraith, Hugh

    2002-12-01

    Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds ('hormones') to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17beta and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17beta as a carcinogen in certain tissues. Now subject to a 'permanent' EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate

  9. [Towards a new vaccine economy?].

    PubMed

    Poirot, P; Martin, J F

    1994-01-01

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

  10. Development of a robust, versatile, and scalable inoculum train for the production of a DNA vaccine.

    PubMed

    Okonkowski, J; Kizer-Bentley, L; Listner, K; Robinson, D; Chartrain, M

    2005-01-01

    For many microbial fermentation processes, the inoculum train can have a substantial impact on process performance in terms of productivity, profitability, and process control. In general, it is understood that a well-characterized and flexible inoculum train is essential for future scale-up and implementation of the process in a pilot plant or manufacturing setting. A fermentation process utilizing E. coli DH5 for the production of plasmid DNA carrying the HIV gag gene for use as a vaccine is currently under development in our laboratory. As part of the development effort, we evaluated inoculum train schemes that incorporate one, two, or three stages. In addition, we investigated the effect of inoculum viable-cell concentrations, either thawed or actively growing, over a wide range (from 2.5 x 10(4) to 1.0 x 10(8) viable cells/mL or approximately 0.001% to 4% of final working volume). The various inoculum trains were evaluated in terms of final plasmid yield, process time, reproducibility, robustness, and feasibility at large scale. The results of these studies show that final plasmid yield remained in the desired range, despite the number of stages or inoculation viable-cell concentrations comprising the inoculum train. On the basis of these observations and because it established a large database, the first part of these investigations supports an exceptional flexibility in the design of scalable inoculum trains for this DNA vaccine process. This work also highlighted that a slightly higher level of process reproducibility, as measured by the time for the culture to reach mid-exponential growth, was observed when using actively growing versus frozen cells. It also demonstrated the existence of a viable-cell concentration threshold for the one-stage process, since we observed that inoculation of the production stage with very low amounts of viable cells from a frozen source could lead to increased process sensitivity to external factors such as variation in the

  11. Enterovirus 71 virus-like particle vaccine: improved production conditions for enhanced yield.

    PubMed

    Chung, Cheng-Yu; Chen, Chi-Yuan; Lin, Shih-Yeh; Chung, Yao-Chi; Chiu, Hsin-Yi; Chi, Wei-Kuang; Lin, Yu-Li; Chiang, Bor-Luen; Chen, Wei-Jheng; Hu, Yu-Chen

    2010-10-01

    To develop the enterovirus 71 (EV71) vaccine, we previously constructed a recombinant baculovirus (Bac-P1-3CD) co-expressing EV71 P1 (under polyhedrin promoter) and 3CD (under p10 promoter) proteins, which caused P1 cleavage by 3CD protease and self-assembly of virus-like particles (VLPs) in Sf-9 cells. Assuming that reducing the 3CD expression can alleviate the competition with P1 expression and elevate the VLPs yield, hereby we constructed Bac-P1-C3CD and Bac-P1-I3CD expressing 3CD under weaker CMV and IE-1 promoters, respectively. Western blot and ELISA analyses revealed that Bac-P1-C3CD and Bac-P1-I3CD led to the VLPs release into the supernatant and enhanced the extracellular VLPs yield in Sf-9 cells, but gave poor VLPs production in High Five™ (Hi-5) cells. By optimizing the process parameters including host cells, cell density, culture mode and dissolved oxygen (DO), the best extracellular VLPs yield was achieved by infecting Sf-9 cells (4 × 10(6)cells/mL) cultured in the bioreactor (DO=30%) with Bac-P1-C3CD, which approached ≈64.3mg/L and represented a ≈43-fold increase over the yield (1.5mg/L) attained using the old process (Bac-P1-3CD infection of Sf-9 cells in the spinner flasks). The resultant VLPs not only resembled the VLPs produced from Bac-P1-3CD infection in density, size and shape, but also induced potent antibody responses in mouse models. The antibodies neutralized EV71 strains of homologous and heterologous genogroups, implicating the potential of the VLPs to confer cross-protection for the prevention of future epidemics. Altogether, Bac-P1-C3CD and the bioprocess render mass production more economical, obviate the need for cell lysis and hold promise for future industrial vaccine production. PMID:20797455

  12. Competency development in antibody production in cancer cell biology

    SciTech Connect

    Park, M.S.

    1998-12-01

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

  13. Biological conversion of pyrolytic products to ethanol and lipids

    NASA Astrophysics Data System (ADS)

    Lian, Jieni

    Pyrolysis is a promising technology that can convert up to 75 % of lignocellulosic biomass into crude bio-oil. However, due to the complex chemical compositions of bio-oil, its further refining into fuels and high value chemicals faces great challenges. This dissertation research proposed new technologies for biological conversion of pyrolytic products derived from cellulose and hemicellulose, such as anhydrosugars and carbolic acids to fuels and chemicals. First, the pyrolytic anhydrosugars (chiefly levoglucosan (LG)) were hydrolysed into glucose followed by neutralization, detoxification and fermentation to produce ethanol by ethanogenetic yeast and lipids by oleaginous yeasts. Second, a novel process for the conversion of C1-C4 pyrolytic products to lipid with oleaginous yeasts was investigated. Third, oleaginous yeasts that can directly convert LG to lipids were studied and a recombined yeast with LG kinase was constructed for the direct convertion of LG into lipids. This allowed a reduction of existing process for LG fermentation from four steps into two steps and eliminated the need for acids and bases as well as the disposal of chemicals. The development of genetic modified organisms with LG kinase opens a promising avenue for the direct LG fermentation to produce a wide range of fuels and chemicals. The simplification of LG utilization process would enhance the economic viability of this technology.

  14. Antibiotic-free production of a herpes simplex virus 2 DNA vaccine in a high yield cGMP process

    PubMed Central

    Nelson, Jared; Rodriguez, Stephen; Finlayson, Neil; Williams, Jim; Carnes, Aaron

    2013-01-01

    Two DNA vaccine plasmids encoding Herpes simplex virus type 2 (HSV-2) glycoprotein D, NTC8485-O2-gD2 and NTC8485-O2-UgD2tr, were produced at large scale under current good manufacturing practice (cGMP) for use in a Phase I human clinical trial. These DNA vaccines incorporate the regulatory agency compliant, minimal, antibiotic-free (AF) NTC8485 mammalian expression vector. Plasmid yields of > 1 g/L were achieved using the HyperGRO™ fed-batch fermentation process, with successful scale up from 10 L process development scale to 320 L culture volume for cGMP production. The DNA vaccines were purified using a low residence time, high shear lysis process and AIRMIXTM technology, followed by chromatographic purification. This combination of optimized plasmid vector, high yield upstream production, and efficient downstream purification resulted in purified HSV-2 DNA vaccines with > 99% total supercoiled plasmid, ≤ 0.2% RNA, ≤ 0.1% host cell genomic DNA, and ≤ 0.1 endotoxin units per mg. PMID:23899469

  15. 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. PMID:26698194

  16. Control strategies against Campylobacter at the poultry production level: biosecurity measures, feed additives and vaccination.

    PubMed

    Meunier, M; Guyard-Nicodème, M; Dory, D; Chemaly, M

    2016-05-01

    Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union, and ranks second in the United States only behind salmonellosis. In Europe, there are about nine million cases of campylobacteriosis every year, making the disease a major public health issue. Human cases are mainly caused by the zoonotic pathogen Campylobacter jejuni. The main source of contamination is handling or consumption of poultry meat. Poultry constitutes the main reservoir of Campylobacter, substantial quantities of which are found in the intestines following rapid, intense colonization. Reducing Campylobacter levels in the poultry chain would decrease the incidence of human campylobacteriosis. As primary production is a crucial step in Campylobacter poultry contamination, controlling the infection at this level could impact the following links along the food chain (slaughter, retail and consumption). This review describes the control strategies implemented during the past few decades in primary poultry production, including the most recent studies. In fact, the implementation of biosecurity and hygiene measures is described, as well as the immune strategy with passive immunization and vaccination trials and the nutritional strategy with the administration of organic and fatty acids, essential oil and plant-derived compound, probiotics, bacteriocins and bacteriophages. PMID:26541243

  17. Sustainable production of biologically active molecules of marine based origin.

    PubMed

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. PMID:23563183

  18. Presence and biological activity of antibiotics used in fuel ethanol and corn co-product production.

    PubMed

    Compart, D M Paulus; Carlson, A M; Crawford, G I; Fink, R C; Diez-Gonzalez, F; Dicostanzo, A; Shurson, G C

    2013-05-01

    Antibiotics are used in ethanol production to control bacteria from competing with yeast for nutrients during starch fermentation. However, there is no published scientific information on whether antibiotic residues are present in distillers grains (DG), co-products from ethanol production, or whether they retain their biological activity. Therefore, the objectives of this study were to quantify concentrations of various antibiotic residues in DG and determine whether residues were biologically active. Twenty distillers wet grains and 20 distillers dried grains samples were collected quarterly from 9 states and 43 ethanol plants in the United States. Samples were analyzed for DM, CP, NDF, crude fat, S, P, and pH to describe the nutritional characteristics of the samples evaluated. Samples were also analyzed for the presence of erythromycin, penicillin G, tetracycline, tylosin, and virginiamycin M1, using liquid chromatography and mass spectrometry. Additionally, virginiamycin residues were determined, using a U.S. Food and Drug Administration-approved bioassay method. Samples were extracted and further analyzed for biological activity by exposing the sample extracts to 10(4) to 10(7) CFU/mL concentrations of sentinel bacterial strains Escherichia coli ATCC 8739 and Listeria monocytogenes ATCC 19115. Extracts that inhibited bacterial growth were considered to have biological activity. Physiochemical characteristics varied among samples but were consistent with previous findings. Thirteen percent of all samples contained low (≤1.12 mg/kg) antibiotic concentrations. Only 1 sample extract inhibited growth of Escherichia coli at 10(4) CFU/mL, but this sample contained no detectable concentrations of antibiotic residues. No extracts inhibited Listeria monocytogenes growth. These data indicate that the likelihood of detectable concentrations of antibiotic residues in DG is low; and if detected, they are found in very low concentrations. The inhibition in only 1 DG

  19. New technologies for influenza vaccines.

    PubMed

    Dormitzer, Philip R; Tsai, Theodore F; Del Giudice, Giuseppe

    2012-01-01

    Influenza vaccine preparations have been administered to humans since the late 1930s, and the diversity of approaches in licensed trivalent seasonal or monovalent pandemic products is unparalleled by vaccines against any other target. These approaches include inactivated whole virus vaccines, detergent or solvent "split" vaccines, subunit vaccines, live attenuated vaccines, adjuvanted vaccines, intramuscular vaccines, intradermal vaccines, intranasal vaccines, egg-produced vaccines and mammalian cell culture-produced vaccines. The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches. This review describes some of the new approaches to influenza immunization that are the subjects of active research and development. PMID:22251994

  20. Polysaccharide-Based Vaccines

    NASA Astrophysics Data System (ADS)

    Santana, Violeta Fernández; Balbin, Yury Valdés; Calderón, Janoi Chang; Icart, Luis Peña; Verez-Bencomo, Vicente

    Capsular polysaccharides (CPS) and lipopolysaccharides from bacteria are employed for the production of vaccines against human diseases. Initial development of CPS as a vaccine was followed by the development and introduction of conjugate polysaccharide-protein vaccines. The principles leading to both developments are reviewed.

  1. Comparing the Primary and Recall Immune Response Induced by a New EV71 Vaccine Using Systems Biology Approaches

    PubMed Central

    Wu, Xing; Mao, Qunying; Chen, Pan; Zhu, Fengcai; Xu, Miao; Kong, Wei; Liang, Zhenglun; Wang, Junzhi

    2015-01-01

    Three inactivated EV71 whole-virus vaccines have completed Phase III clinical trials in mainland China, with high efficacy, satisfactory safety, and sustained immunogenicity. However, the molecular mechanisms how this new vaccine elicit potent immune response remain poorly understood. To characterize the primary and recall responses to EV71 vaccines, PBMC from 19 recipients before and after vaccination with EV71 vaccine are collected and their gene expression signatures after stimulation with EV71 antigen were compared. The results showed that primary and recall response to EV71 antigen have both activated an IRF7 regulating type I interferon and antiviral immune response network. However, up-regulated genes involved in T cell activation regulated by IRF1, inflammatory response, B-cell activation and humoral immune response were only observed in recall response. The specific secretion of IL-10 in primary response and IL-2,IP-10,CCL14a, CCL21 in recall response was consistent with the activation of immune response process found in genes. Furthermore, the expression of MX1 and secretion of IP-10 in recall response were strongly correlated with NTAb level at 180d after vaccination (r = 0.81 and 0.99). In summary, inflammatory response, adaptive immune response and a stronger antiviral response were indentified in recall response. PMID:26465882

  2. Pseudovirion Particle Production by Live Poxvirus Human Immunodeficiency Virus Vaccine Vector Enhances Humoral and Cellular Immune Responses

    PubMed Central

    Chen, Xuemin; Rock, Michael T.; Hammonds, Jason; Tartaglia, James; Shintani, Ayumi; Currier, Jeff; Slike, Bonnie; Crowe, James E.; Marovich, Mary; Spearman, Paul

    2005-01-01

    Live-vector-based human immunodeficiency virus (HIV) vaccines are an integral part of a number of HIV vaccine regimens currently under evaluation. Live vectors that carry an intact gag gene are capable of eliciting HIV pseudovirion particle formation from infected host cells. The impact of pseudovirion particle formation on the immune response generated by live HIV vaccine vectors has not been established. In this study, a canarypox HIV vaccine candidate vector expressing HIV gag and env genes, vCP205, was modified by the introduction of a glycine-to-alanine coding change in the N-terminal myristylation site of gag to create Myr− vCP205. This substitution effectively eliminated particle formation without altering the level of protein production. vCP205 and Myr− vCP205 were then directly compared for the ability to induce HIV-specific immune responses in mice. The particle-competent vector vCP205 elicited higher levels of CD8+ T-cell responses, as indicated by gamma interferon enzyme-linked immunospot (ELISPOT) assay and intracellular cytokine staining. Humoral responses to Gag and Env were also markedly higher from animals immunized with the particle-competent vector. Furthermore, HIV-specific CD4+ T-cell responses were greater among animals immunized with the particle-competent vector. Using a human dendritic cell model of antigen presentation in vitro, vCP205 generated greater ELISPOT responses than Myr− vCP205. These results demonstrate that pseudovirion particle production by live-vector HIV vaccines enhances HIV-specific cellular and humoral immune responses. PMID:15827168

  3. Pseudovirion particle production by live poxvirus human immunodeficiency virus vaccine vector enhances humoral and cellular immune responses.

    PubMed

    Chen, Xuemin; Rock, Michael T; Hammonds, Jason; Tartaglia, James; Shintani, Ayumi; Currier, Jeff; Slike, Bonnie; Crowe, James E; Marovich, Mary; Spearman, Paul

    2005-05-01

    Live-vector-based human immunodeficiency virus (HIV) vaccines are an integral part of a number of HIV vaccine regimens currently under evaluation. Live vectors that carry an intact gag gene are capable of eliciting HIV pseudovirion particle formation from infected host cells. The impact of pseudovirion particle formation on the immune response generated by live HIV vaccine vectors has not been established. In this study, a canarypox HIV vaccine candidate vector expressing HIV gag and env genes, vCP205, was modified by the introduction of a glycine-to-alanine coding change in the N-terminal myristylation site of gag to create Myr- vCP205. This substitution effectively eliminated particle formation without altering the level of protein production. vCP205 and Myr- vCP205 were then directly compared for the ability to induce HIV-specific immune responses in mice. The particle-competent vector vCP205 elicited higher levels of CD8+ T-cell responses, as indicated by gamma interferon enzyme-linked immunospot (ELISPOT) assay and intracellular cytokine staining. Humoral responses to Gag and Env were also markedly higher from animals immunized with the particle-competent vector. Furthermore, HIV-specific CD4+ T-cell responses were greater among animals immunized with the particle-competent vector. Using a human dendritic cell model of antigen presentation in vitro, vCP205 generated greater ELISPOT responses than Myr- vCP205. These results demonstrate that pseudovirion particle production by live-vector HIV vaccines enhances HIV-specific cellular and humoral immune responses. PMID:15827168

  4. Miocene Global Carbon Isotope Shifts and Marine Biological Productivity.

    NASA Astrophysics Data System (ADS)

    Diester-Haass, L.; Billups, K.

    2005-12-01

    The Miocene contains two major global carbon isotope shifts: a negative shift during the late Miocene (~8-6 Ma) and a positive shift during the mid-Miocene (16-14 Ma). We aim at deciphering possible changes in marine biological export productivity during these shifts by calculating paleoproductivity in gC/cm*ky from benthic foraminiferal numbers and accumulation rates at a number of sites spanning the world oceans. Our previous work has illustrated that the onset of the late Miocene negative d 13C shift, which has been attributed to enhanced erosion of terrestrial biomass and expansion of C4 plants, is also accompanied by an increase in marine export productivity from lower than present day values up to 2-3 times modern values at six sites (982, 1088, 721, 846, 1146, 1172; Diester-Haass et al, in press; Diester-Haass et al., in preparation). The Mid-Miocene 'Monterey Event', on the other hand, has been attributed to sequestration of organic material in circum-Pacific basins (Vincent and Berger, 1985) or wide spread deposition of brown coal and drowning of carbonate platforms (Föllmi et al., 2005) . For this particular time interval, our initial results from Site 608 (Atlantic Ocean) reveal relatively constant paleoproductivity values similar to modern ones ( about 10 gC/cm*ky) until 16.5 Ma, after which time paleoproductivity begins to increase until the end of our record at 11 Ma. Superimposed on the trend of generally increasing productivity, there are a number of productivity minima spaced roughly 0.5 million years apart. The long term trend in the paleoproductivity finds some similarities in the global composite benthic foraminiferal d 13C record as both proxies show an overall increase until ~14 Ma. Thereafter, however, paleoproductivity continues to increase while d 13C values decrease marking the end of the Monterey excursion. Stable isotope analyses from these same intervals will show to what extend the smaller scale fluctuations in paleoproductivity can

  5. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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 product imported for research and evaluation under a permit issued in accordance with § 104.4, with...

  6. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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 product imported for research and evaluation under a permit issued in accordance with § 104.4, with...

  7. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  8. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  9. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  10. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  11. Integrated anaerobic/aerobic biological treatment for intensive swine production.

    PubMed

    Bortone, Giuseppe

    2009-11-01

    Manure processing could help farmers to effectively manage nitrogen (N) surplus load. Many pig farms have to treat wastewater. Piggery wastewater treatment is a complex challenge, due to the high COD and N concentrations and low C/N ratio. Anaerobic digestion (AD) could be a convenient pre-treatment, particularly from the energetic view point and farm income, but this causes further reduction of C/N ratio and makes denitrification difficult. N removal can only be obtained integrating anaerobic/aerobic treatment by taking into account the best use of electron donors. Experiences gained in Italy during development of integrated biological treatment approaches for swine manure, from bench to full scale, are reported in this paper. Solid/liquid separation as pre-treatment of raw manure is an efficient strategy to facilitate liquid fraction treatment without significantly lowering C/N ratio. In Italy, two full scale SBRs showed excellent efficiency and reliability. Current renewable energy policy and incentives makes economically attractive the application of AD to the separated solid fraction using high solid anaerobic digester (HSAD) technology. Economic evaluation showed that energy production can reduce costs up to 60%, making sustainable the overall treatment. PMID:19135363

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

    SciTech Connect

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

    2012-05-18

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

  13. Field efficacy of an inactivated bivalent influenza vaccine in a multi-site swine production system during an outbreak of systemic porcine circovirus associated disease.

    PubMed

    Poljak, Zvonimir; Dewey, Catherine E; Martin, S Wayne; Christensen, Jette; Friendship, Robert M

    2010-04-01

    Swine influenza (SI) is a disease of significance for the swine industry, and vaccination is often recommended as a way to reduce its impact on production. The efficacy of SI vaccines is well established under experimental conditions, but information about field efficacy is scarce. The objective of this study was to evaluate the efficacy of a commercial inactivated bivalent (H1N1/H3N2) vaccine under conditions of natural exposure to a field SI variant. To accomplish our goal we used a randomized, blinded, field trial in 2 cohorts of finisher pigs in a multi-site swine production system located in southern Ontario. During the trial, this herd experienced an outbreak of porcine circovirus associated disease (PCVAD). The efficacy of the SI vaccine was assessed through its effect on average daily weight gain, and serological responses to SI over time. The effect of vaccination on pig growth was different in the 2 cohorts. Weight gain was higher in vaccinated pigs than in control pigs in Cohort 1, but was numerically higher for control pigs than for vaccinated pigs in Cohort 2. Vaccination against swine influenza, in a herd experiencing an outbreak of PCVAD, was of questionable value. PMID:20592840

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

    PubMed

    Torres, Yaniel; Viña, Silvio

    2012-01-01

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

  15. Occupational infection due to Brucella abortus S19 among workers involved in vaccine production in Argentina.

    PubMed

    Wallach, J C; Ferrero, M C; Victoria Delpino, M; Fossati, C A; Baldi, P C

    2008-08-01

    The pathological consequences of exposure to the vaccine strain Brucella abortus S19 were evaluated in 30 employees from vaccine-manufacturing plants. Active brucellosis was diagnosed in 21 subjects, of whom only five recalled an accidental exposure. Clinical manifestations were mild, and only one patient presented a complication. After antimicrobial therapy, initially symptomatic patients either experienced clinical remission or had mild persistent symptoms. This is the first study reporting infection by B. abortus S19 among workers from vaccine-manufacturing plants, which in many cases was acquired from unnoticed exposures. Measures to improve the safety of B. abortus S19 handling should be implemented. PMID:18727806

  16. Development of biological platform for the autotrophic production of biofuels

    NASA Astrophysics Data System (ADS)

    Khan, Nymul

    The research described herein is aimed at developing an advanced biofuel platform that has the potential to surpass the natural rate of solar energy capture and CO2 fixation. The underlying concept is to use the electricity from a renewable source, such as wind or solar, to capture CO 2 via a biological agent, such as a microbe, into liquid fuels that can be used for the transportation sector. In addition to being renewable, the higher rate of energy capture by photovoltaic cells than natural photosynthesis is expected to facilitate higher rate of liquid fuel production than traditional biofuel processes. The envisioned platform is part of ARPA-E's (Advanced Research Projects Agency - Energy) Electrofuels initiative which aims at supplementing the country's petroleum based fuel production with renewable liquid fuels that can integrate easily with the existing refining and distribution infrastructure (http://arpae. energy.gov/ProgramsProjects/Electrofuels.aspx). The Electrofuels initiative aimed to develop liquid biofuels that avoid the issues encountered in the current generation of biofuels: (1) the reliance of biomass-derived technologies on the inefficient process of photosynthesis, (2) the relatively energy- and resource-intensive nature of agronomic processes, and (3) the occupation of large areas of arable land for feedstock production. The process proceeds by the capture of solar energy into electrical energy via photovoltaic cells, using the generated electricity to split water into molecular hydrogen (H2) and oxygen (O2), and feeding these gases, along with carbon dioxide (CO2) emitted from point sources such as a biomass or coal-fired power plant, to a microbial bioprocessing platform. The proposed microbial bioprocessing platform leverages a chemolithoautotrophic microorganism (Rhodobacter capsulatus or Ralstonia eutropha) naturally able to utilize these gases as growth substrates, and genetically modified to produce a triterpene hydrocarbon fuel

  17. Vaccines against poverty

    PubMed Central

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

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

  18. WHO Expert Committee on Biological Standardization.

    PubMed

    2013-01-01

    This report presents the recommendations of a WHO expert committee commissioned to coordinate activities leading to the adoption of international recommendations for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the attention of the Committee and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, endocrinological substances and in vitro diagnostic devices. The second part of the report, of particular relevance to manufacturers and national regulatory authorities, contains revised WHO Recommendations for evaluation of animal cell cultures as substrates for the manufacture of biological medicinal products, for production and control of hepatitis B vaccines and for production and control of yellow fever vaccines. New WHO Guidelines on the independent lot release of vaccines are also included. Finally, there is an update to the procedure for the prequalification of vaccines. Also included are lists of Recommendations, Guidelines and other documents related to the manufacture and control of biological substances used in medicine, and of International Standards and Reference Reagents for biological substances. PMID:24340794

  19. Gardasil® – The New HPV Vaccine: The Right Product, the Right Time? A Commentary

    PubMed Central

    Lexchin, Joel; Arya, Neil; Singh, Sonal

    2010-01-01

    The federal and provincial governments have undertaken a universal immunization program to protect school-aged girls against cervical cancer using the new human papillomavirus vaccine Gardasil®. While the vaccine appears to be effective and safe, there are a number of important unanswered questions regarding it and the effects of the immunization program. Here we briefly review key literature about the vaccine and then use the Erickson criteria, which offer an evidence basis for decision-making regarding national immunization strategies, to evaluate whether the program is congruent with sound public health policy. Our analysis of the national decision to recommend and fund a vaccination program using Gardasil® raises significant questions about the basis for this program. PMID:21532767

  20. New approaches and omics tools for mining of vaccine candidates against vector-borne diseases.

    PubMed

    Kuleš, Josipa; Horvatić, Anita; Guillemin, Nicolas; Galan, Asier; Mrljak, Vladimir; Bhide, Mangesh

    2016-08-16

    Vector-borne diseases (VBDs) present a major threat to human and animal health, as well as place a substantial burden on livestock production. As a way of sustainable VBD control, focus is set on vaccine development. Advances in genomics and other "omics" over the past two decades have given rise to a "third generation" of vaccines based on technologies such as reverse vaccinology, functional genomics, immunomics, structural vaccinology and the systems biology approach. The application of omics approaches is shortening the time required to develop the vaccines and increasing the probability of discovery of potential vaccine candidates. Herein, we review the development of new generation vaccines for VBDs, and discuss technological advancement and overall challenges in the vaccine development pipeline. Special emphasis is placed on the development of anti-tick vaccines that can quell both vectors and pathogens. PMID:27384976

  1. Production of a subunit vaccine candidate against porcine post-weaning diarrhea in high-biomass transplastomic tobacco.

    PubMed

    Kolotilin, Igor; Kaldis, Angelo; Devriendt, Bert; Joensuu, Jussi; Cox, Eric; Menassa, Rima

    2012-01-01

    Post-weaning diarrhea (PWD) in piglets is a major problem in piggeries worldwide and results in severe economic losses. Infection with Enterotoxigenic Escherichia coli (ETEC) is the key culprit for the PWD disease. F4 fimbriae of ETEC are highly stable proteinaceous polymers, mainly composed of the major structural subunit FaeG, with a capacity to evoke mucosal immune responses, thus demonstrating a potential to act as an oral vaccine against ETEC-induced porcine PWD. In this study we used a transplastomic approach in tobacco to produce a recombinant variant of the FaeG protein, rFaeG(ntd/dsc), engineered for expression as a stable monomer by N-terminal deletion and donor strand-complementation (ntd/dsc). The generated transplastomic tobacco plants accumulated up to 2.0 g rFaeG(ntd/dsc) per 1 kg fresh leaf tissue (more than 1% of dry leaf tissue) and showed normal phenotype indistinguishable from wild type untransformed plants. We determined that chloroplast-produced rFaeG(ntd/dsc) protein retained the key properties of an oral vaccine, i.e. binding to porcine intestinal F4 receptors (F4R), and inhibition of the F4-possessing (F4+) ETEC attachment to F4R. Additionally, the plant biomass matrix was shown to delay degradation of the chloroplast-produced rFaeG(ntd/dsc) in gastrointestinal conditions, demonstrating a potential to function as a shelter-vehicle for vaccine delivery. These results suggest that transplastomic plants expressing the rFaeG(ntd/dsc) protein could be used for production and, possibly, delivery of an oral vaccine against porcine F4+ ETEC infections. Our findings therefore present a feasible approach for developing an oral vaccination strategy against porcine PWD. PMID:22879967

  2. Production of a Particulate Hepatitis C Vaccine Candidate by an Engineered Lactococcus lactis Strain▿

    PubMed Central

    Parlane, Natalie A.; Grage, Katrin; Lee, Jason W.; Buddle, Bryce M.; Denis, Michel; Rehm, Bernd H. A.

    2011-01-01

    Vaccine delivery systems based on display of antigens on bioengineered bacterial polyester inclusions can stimulate cellular immune responses. The food-grade Gram-positive bacterium Lactococcus lactis was engineered to produce spherical polyhydroxybutyrate (PHB) inclusions which abundantly displayed the hepatitis C virus core (HCc) antigen. In mice, the immune response induced by this antigen delivery system was compared to that induced by vaccination with HCc antigen displayed on PHB beads produced in Escherichia coli, to PHB beads without antigen produced in L. lactis or E. coli, or directly to the recombinant HCc protein. Vaccination site lesions were minimal in all mice vaccinated with HCc PHB beads or recombinant protein, all mixed in the oil-in-water adjuvant Emulsigen, while vaccination with the recombinant protein in complete Freund's adjuvant produced a marked inflammatory reaction at the vaccination site. Vaccination with the PHB beads produced in L. lactis and displaying HCc antigen produced antigen-specific cellular immune responses with significant release of gamma interferon (IFN-γ) and interleukin-17A (IL-17A) from splenocyte cultures and no significant antigen-specific serum antibody, while the PHB beads displaying HCc but produced in E. coli released IFN-γ and IL-17A as well as the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-6 and low levels of IgG2c antibody. In contrast, recombinant HCc antigen in Emulsigen produced a diverse cytokine response and a strong IgG1 antibody response. Overall it was shown that L. lactis can be used to produce immunogenic PHB beads displaying viral antigens, making the beads suitable for vaccination against viral infections. PMID:21984246

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

    NASA Astrophysics Data System (ADS)

    Kim, Jonathan Philip

    Mercury volatilization and oceanic evasion to the atmosphere were investigated in the tropical Pacific Ocean with emphasis on the biologically productive equatorial region. Further studies were conducted at two stations in the oligiotrophic North Pacific gyre, and in the estuarine mesocosms at the Marine Ecosystems Research Laboratory (MERL), University of Rhode Island. Dissolved gaseous Hg (DGM) in the tropical Pacific along 150^circ W at 4 stations (10^circ N, 0^ circ, 5^circ S, 12^circ S) ranged from 35-85 femtomoles per liter (fM) in surface waters and from 105-185 fM in deeper waters (350-400 meters). Speciation experiments indicated that Hg^circ was the dominant form in surface waters, while evidence for (CH_3)_2Hg was found at depth. The increases of DGM with depth are consistent with a volatile Hg source in deeper waters. A significant correlation between DGM and apparent oxygen utilization (n = 23, r = 0.694) suggested bacterial methylation of Hg in the oxygen minimum zone. In equatorial Pacific surface waters (155-95 ^circ W), DGM varied between 60 and 225 fM. Elemental Hg appears to comprise the major fraction of DGM. Elevated DGM concentrations corresponded with increased chlorophyll a levels and cooler, nutrient-rich waters. These results suggest that phytoplankton might volatilize Hg in surface seawater or bacteria could produce Hg^circ in deeper waters which upwell to the sea surface. Surface waters of the equatorial Pacific were supersaturated with respect to Hg^circ (179-1769%). Local Hg effluxes, estimated with a thin-film gas exchange model, were between 225 and 1050 pmoles/m^2day. The anual Hg efflux from the equatorial Pacific, 1.6 +/- 1.3 times 10^{+6 } moles (megamoles), was estimated at 4-5% of the total global Hg flux to the atmosphere. When normalized to primary production, a yearly Hg efflux of 14 +/- 9 megamoles was predicted for the oceans. This is about 35% of the annual atmospheric Hg flux and is comparable to human-derived Hg

  4. Rapid and Scalable Plant-based Production of a Cholera Toxin B Subunit Variant to Aid in Mass Vaccination against Cholera Outbreaks

    PubMed Central

    Bennett, Lauren J.; Baldauf, Keegan J.; Kajiura, Hiroyuki; Fujiyama, Kazuhito; Matoba, Nobuyuki

    2013-01-01

    Introduction Cholera toxin B subunit (CTB) is a component of an internationally licensed oral cholera vaccine. The protein induces neutralizing antibodies against the holotoxin, the virulence factor responsible for severe diarrhea. A field clinical trial has suggested that the addition of CTB to killed whole-cell bacteria provides superior short-term protection to whole-cell-only vaccines; however, challenges in CTB biomanufacturing (i.e., cost and scale) hamper its implementation to mass vaccination in developing countries. To provide a potential solution to this issue, we developed a rapid, robust, and scalable CTB production system in plants. Methodology/Principal Findings In a preliminary study of expressing original CTB in transgenic Nicotiana benthamiana, the protein was N-glycosylated with plant-specific glycans. Thus, an aglycosylated CTB variant (pCTB) was created and overexpressed via a plant virus vector. Upon additional transgene engineering for retention in the endoplasmic reticulum and optimization of a secretory signal, the yield of pCTB was dramatically improved, reaching >1 g per kg of fresh leaf material. The protein was efficiently purified by simple two-step chromatography. The GM1-ganglioside binding capacity and conformational stability of pCTB were virtually identical to the bacteria-derived original B subunit, as demonstrated in competitive enzyme-linked immunosorbent assay, surface plasmon resonance, and fluorescence-based thermal shift assay. Mammalian cell surface-binding was corroborated by immunofluorescence and flow cytometry. pCTB exhibited strong oral immunogenicity in mice, inducing significant levels of CTB-specific intestinal antibodies that persisted over 6 months. Moreover, these antibodies effectively neutralized the cholera holotoxin in vitro. Conclusions/Significance Taken together, these results demonstrated that pCTB has robust producibility in Nicotiana plants and retains most, if not all, of major biological activities of

  5. Development of biological platform for the autotrophic production of biofuels

    NASA Astrophysics Data System (ADS)

    Khan, Nymul

    The research described herein is aimed at developing an advanced biofuel platform that has the potential to surpass the natural rate of solar energy capture and CO2 fixation. The underlying concept is to use the electricity from a renewable source, such as wind or solar, to capture CO 2 via a biological agent, such as a microbe, into liquid fuels that can be used for the transportation sector. In addition to being renewable, the higher rate of energy capture by photovoltaic cells than natural photosynthesis is expected to facilitate higher rate of liquid fuel production than traditional biofuel processes. The envisioned platform is part of ARPA-E's (Advanced Research Projects Agency - Energy) Electrofuels initiative which aims at supplementing the country's petroleum based fuel production with renewable liquid fuels that can integrate easily with the existing refining and distribution infrastructure (http://arpae. energy.gov/ProgramsProjects/Electrofuels.aspx). The Electrofuels initiative aimed to develop liquid biofuels that avoid the issues encountered in the current generation of biofuels: (1) the reliance of biomass-derived technologies on the inefficient process of photosynthesis, (2) the relatively energy- and resource-intensive nature of agronomic processes, and (3) the occupation of large areas of arable land for feedstock production. The process proceeds by the capture of solar energy into electrical energy via photovoltaic cells, using the generated electricity to split water into molecular hydrogen (H2) and oxygen (O2), and feeding these gases, along with carbon dioxide (CO2) emitted from point sources such as a biomass or coal-fired power plant, to a microbial bioprocessing platform. The proposed microbial bioprocessing platform leverages a chemolithoautotrophic microorganism (Rhodobacter capsulatus or Ralstonia eutropha) naturally able to utilize these gases as growth substrates, and genetically modified to produce a triterpene hydrocarbon fuel

  6. 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

  7. Analysis of the landscape of biologically-derived pharmaceuticals in Europe: dominant production systems, molecule types on the rise and approval trends.

    PubMed

    Kyriakopoulos, Sarantos; Kontoravdi, Cleo

    2013-02-14

    A thorough sort of the human drugs approved by the European Medicines Agency (EMA) between its establishment in 1995 until June 2012 is presented herein with a focus on biologically-derived pharmaceuticals. Over 200 (33%) of the 640 approved therapeutic drugs are derived from natural sources, produced via recombinant DNA technology, or generated through virus propagation. A breakdown based on production method, type of molecule and therapeutic category is presented. Current EMA approvals demonstrate that mammalian cells are the only choice for glycoprotein drugs, with Chinese hamster ovary cells being the dominant hosts for their production. On the other hand, bacterial cells and specifically Escherichia coli are the dominant hosts for protein-based drugs, followed by the yeast Saccharomyces cerevisiae. The latter is the dominant host for recombinant vaccine production, although egg-based production is still the main platform of vaccine provision. Our findings suggest that the majority of biologically-derived drugs are prescribed for cancer and related conditions, as well as the treatment of diabetes. The approval rate for biologically-derived drugs shows a strong upward trend for monoclonal antibodies and fusion proteins since 2009, while hormones, antibodies and growth factors remain the most populous categories. Despite a clear pathway for the approval of biosimilars set by the EMA and their potential to drive sales growth, we have only found approved biosimilars for three molecules. In 2012 there appears to be a slow-down in approvals, which coincides with a reported decline in the growth rate of biologics sales. PMID:23262060

  8. Product-specific validation of a serological potency test for release of Leptospira vaccines in the European Union.

    PubMed

    Stirling, Catrina; Novokova, Viera

    2013-09-01

    Historically in the European Union, all Leptospira vaccines were released using the European Pharmacopoeia (Ph. Eur.) hamster potency assay. Recently, there has been a shift toward alternatives that offer either refinement of testing or replacement of animals for product release. This is being driven by animal welfare concerns but also by a drive to have more consistent, cheaper, and faster batch release tests. This publication discusses one such example of a multicomponent canine vaccine that includes three Leptospira serovars and has recently been registered in the European Union. The potency release test is a refinement because it uses rabbit serology rather than hamster challenge. This publication covers the principles of the test method, challenges faced during its development and registration, and discussion about benefits and limitations of this method. It concludes with a view of how the use of serology testing could fit into an overall strategy to move to fully in vitro testing by adopting a consistency approach. PMID:23849308

  9. Problems with E-Cigarettes, Vape Products, Hookah, Cigarettes or Tobacco? Tell FDA

    MedlinePlus

    ... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products ... To report problems with tobacco products, go to the Safety Reporting Portal Get Consumer Updates by E-mail ...

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

    PubMed

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

    2012-01-01

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

  11. Milk and Serum J5-Specific Antibody Responses, Milk Production Change, and Clinical Effects following Intramammary Escherichia coli Challenge for J5 Vaccinate and Control Cows▿

    PubMed Central

    Wilson, David J.; Mallard, Bonnie A.; Burton, Jeanne L.; Schukken, Ynte H.; Gröhn, Yrjo T.

    2007-01-01

    Holstein dairy cows (four J5 vaccinates and four controls) selected for no recorded intramammary disease and low somatic cell count (SCC) during the previous lactation were challenged by intramammary infusion of Escherichia coli. Vaccination with J5 was at 8 weeks and again 4 weeks before the anticipated calving date. Cows were challenged at 8 to 16 days in milk (DIM). Shedding of E. coli in milk was significantly higher among controls than vaccinates (no shedding) from 6 h to 21 h postchallenge. From 21 h to 132 h postchallenge, SCC in challenged quarters of controls (5,429,000/ml) was significantly higher than that of vaccinates (490,000/ml). On the day after challenge, milk production in control cows was 8 kg less, while vaccinates gained 0.5 kg, a significant difference. In serum immediately prior to challenge, J5-specific immunoglobulin G1 (IgG1) was significantly higher, IgG2 was nearly significantly higher, and IgM was the same in J5 vaccinates relative to controls. Vaccinates had proportionally more IgG2 in serum postcalving and in the first 12 h following challenge and less IgG2 in milk 24 h after challenge than the controls, approaching statistical significance. The ratio of J5-specific IgG1 and IgG2 combined compared to IgM was significantly higher in vaccinates than in controls in prechallenge serum (ratios of 15.8 and 3.2, respectively) and milk (5.0 and 1.3, respectively). Cows with higher IgM titers in milk 12 h postchallenge produced significantly less milk. Vaccination with J5 was significantly associated with higher production of J5-specific IgG1 and IgG2 in early lactation, reduced SCC, faster clearance of E. coli from milk, and less milk production loss following intramammary challenge. PMID:17460115

  12. A Live Oral Fowl Typhoid Vaccine with Reversible O-Antigen Production.

    PubMed

    Mitra, Arindam; Łaniewski, Paweł; Curtiss, Roy; Roland, Kenneth L

    2015-03-01

    Salmonella enterica serovar Gallinarum causes fowl typhoid, recognized worldwide as an economically important disease. The current vaccine, 9R, lacks a complete O antigen, which is a Salmonella virulence factor, and, in addition, has a number of other less well characterized chromosomal mutations. For optimal efficacy, 9R is administered by injection. In an effort to develop a vaccine suitable for oral administration, we constructed Salmonella Gallinarum strains with a reversible O-antigen phenotype. In this scenario, the vaccine strain produces full-length O antigen at the time it is administered to birds. After the vaccine has had time to colonize internal lymphoid tissues, the O-antigen is gradually lost, resulting in an attenuated strain. We found that strains carrying single mutations conferring this phenotype, Apmi and arabinose-regulated rfc, retained virulence. However, a mutant strain carrying both of these mutations was completely attenuated and immunogenic in chickens. This work demonstrates a novel approach for developing live Salmonella vaccines for poultry. PMID:26292534

  13. Influences of F-strain Mycoplasma gallisepticum vaccine on productive and reproductive performance of commercial parent broiler chicken breeders on a multi-age farm.

    PubMed

    Liu, J J; Ding, L; Wei, J Z; Li, Y

    2013-06-01

    The influences of F-strain Mycoplasma gallisepticum (FMG) vaccine inoculation during the pullet period on the subsequent productive and reproductive performance of parent broiler chicken breeders on a multi-age farm were evaluated. Three thousand breeders were randomly divided into 2 treatment groups that were either vaccinated with FMG (FMG-vaccinated group) or not vaccinated with FMG (FMG-free group). Body weight and egg production were determined through approximately 50 wk of age. Egg weight and feed conversion was determined at 26, 32, 35, 38, and 43 wk of age. Egg quality parameters, including eggshell strength, egg-specific gravity, egg shape index, blood-meat spots, Haugh unit score, eggshell thickness, yolk:albumen ratio, percentage yolk, albumen and eggshell weights, and percentage fertility, hatchability, and second-quality chicks were determined at 26, 32, and 43 wk of age. Air sacs were examined and lesions were scored at 20, 32, and 50 wk of age. The number of mature ovarian follicles, histologies of ovary, and lengths, and histologies of the infundibulum, magnum, isthmus, uterus, and vagina were determined. In the present study, an increase in egg production of broiler breeder hens in the FMG-vaccinated group during peak of lay was compared with the FMG-free group. Feed conversion of hens in the FMG-vaccinated group was significantly less at 32, 35, 38, and 43 wk of age. Eggs from hens in the FMG-vaccinated group had a significantly higher Haugh units score at 26 wk of age and had a significantly higher eggshell thickness and lower incidence of blood-meat spots at 32 wk. Hatching eggs from hens in the FMG-vaccinated group had a significantly higher hatchability. The mean lesion score of air-sac lesion of birds in the FMG-vaccinated group was significantly less than FMG-vaccinated group. Uteruses of hens in the FMG-vaccinated group had a significantly longer length compared with the FMG-free group at 32 wk of age. The results indicate that inoculation

  14. Polio Vaccination

    MedlinePlus

    ... inactive polio vaccine OPV=oral polio vaccine Polio Vaccination Pronounced [PO-lee-oh] Recommend on Facebook Tweet ... handling and storage Related Pages Global Vaccines and Immunization Global Polio Also Known As & Abbreviations Polio=poliomyelitis ...

  15. [Viruses as biological weapons].

    PubMed

    Akçali, Alper

    2005-07-01

    The destruction made by nuclear, biological and chemical weapons used by governments and terrorist groups in the near history is posing anxiety and fear for human being. Rumour about the possible use of these agents leads to the development of serious negative effects on populations. Since there are no vaccine and therapy for most viral agents and cost of production as biological weapons is low, interest rate is rising for viruses. In this review, general characteristics, diagnosis, therapy and protective measures for viral agents such as variola virus, hemorrhagic fever viruses, encephalitis viruses, Hantaviruses and Nipah viruses, those can be used as biological weapon, have been summarized. PMID:16358499

  16. 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. PMID:26922984

  17. Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites.

    PubMed

    Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup; Weber, Tilmann

    2016-08-27

    Covering: 2012 to 2016Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites. The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production. PMID:27072921

  18. Development of Rabies Virus-Like Particles for Vaccine Applications: Production, Characterization, and Protection Studies.

    PubMed

    Fontana, Diego; Etcheverrigaray, Marina; Kratje, Ricardo; Prieto, Claudio

    2016-01-01

    Rabies is a viral infection of the central nervous system for which vaccination is the only treatment possible. Besides preexposure, vaccination is highly recommended for people living in endemic areas, veterinarians, and laboratory workers. Our group has developed rabies virus-like particles (RV-VLPs) with immunogenic features expressed in mammalian cells for vaccine applications. In this chapter the methods to obtain and characterize a stable HEK293 cell line expressing RV-VLPs are detailed. Further, analytical ultracentrifugation steps to purify the obtained VLPs are developed, as well as western blot, dynamic light scattering, and immunogold electron microscopy to analyze the size, distribution, shape, and antigenic conformation of the purified particles. Finally, immunization protocols are described to study the immunogenicity of RV-VLPs. PMID:27076129

  19. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false U.S. Veterinary Biological Product License. 102.5 Section 102.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES...

  20. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false U.S. Veterinary Biological Product License. 102.5 Section 102.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES...

  1. 9 CFR 113.53 - Requirements for ingredients of animal origin used for production of biologics.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Requirements for ingredients of animal origin used for production of biologics. 113.53 Section 113.53 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Requirements for ingredients of animal origin used for production of biologics. 113.53 Section 113.53 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  3. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Requirements for cell lines used for production of biologics. 113.52 Section 113.52 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS...

  4. The large-scale production of an artificial influenza virus-like particle vaccine in silkworm pupae.

    PubMed

    Nerome, Kuniaki; Sugita, Shigeo; Kuroda, Kazumichi; Hirose, Toshiharu; Matsuda, Sayaka; Majima, Kei; Kawasaki, Kazunori; Shibata, Toshikatsu; Poetri, Okti Nadia; Soejoedono, Retno D; Mayasari, Ni L P Ika; Agungpriyono, Srihadi; Nerome, Reiko

    2015-01-01

    We successfully established a mass production system for an influenza virus-like particle (VLP) vaccine using a synthetic H5 hemagglutinin (HA) gene codon-optimized for the silkworm. A recombinant baculovirus containing the synthetic gene was inoculated into silkworm pupae. Four days after inoculation, the hemagglutination titer in homogenates from infected pupae reached a mean value of 0.8 million hemagglutination units (HAU), approximately 2,000 μg HA protein per pupa, more than 50-fold higher than that produced with an embryonated chicken egg. VLPs ranging from 30 nm to 300 nm in diameter and covered with a large number of spikes were detected in the homogenates. The spikes were approximately 14 nm long, similar to an authentic influenza HA spike. Detailed electron micrographs indicated that the VLP spike density was similar to that of authentic influenza virus particles. The results clearly show that the expression of a single HA gene can efficiently produce VLPs in silkworm pupae. When chickens were immunized with the pupae homogenate, the hemagglutination inhibition titer in their sera reached values of 2,048-8,192 after approximately 1 month. This is the first report demonstrating that a large amount of VLP vaccine could be produced by single synthetic HA gene in silkworm pupae. Our system might be useful for future vaccine development against other viral diseases. PMID:25448101

  5. Complement fixing antibody production in thymectomized Oncorhynchus mykiss, vaccinated against or infected with the pathogenic haemoflagellate Cryptobia salmositica.

    PubMed

    Feng, S; Woo, P T

    1997-01-01

    Short-term thymectomized (two months after thymectomy) adult rainbow trout, Oncorhynchus mykiss (Walbaum) infected with the flagellate Cryptobia salmositica Katz, 1951 responded well during primary infection with C. salmositica and recovered fish also showed secondary response (rapid production of complement fixing antibody after homologous challenge) five months after recovery. Complement fixing antibody was detected during primary and secondary responses and the titres of complement fixing antibody in thymectomized fish were significantly lower than those in infected intact fish. The parasitaemia in thymectomized infected fish was significantly lower than in intact infected fish. Both recovered thymectomized fish and intact fish were protected from cryptobiosis when they were challenged. Similarly, long-term thymectomized fish (nine months after thymectomy) vaccinated with an attenuated strain of C. salmositica were protected from cryptobiosis. There were no significant difference (P > 0.05) in parasitaemia, packed cell volume and complement fixing antibody titres between vaccinated/challenged thymectomized and vaccinated/challenged intact fish. Hence, thymectomy in adult rainbow trout did not decrease the detectable complement fixing antibody against C. salmositica in long-term thymectomized fish but reduced the detectable protective antibody in short-term thymectomized fish. PMID:9332978

  6. Synthetic biology for microbial production of lipid-based biofuels.

    PubMed

    d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

    2015-12-01

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing. PMID:26479184

  7. Molecular basis of vaccination.

    PubMed

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

    1998-02-01

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

  8. Effect of vaccine administration modality on immunogenicity and efficacy.

    PubMed

    Zhang, Lu; Wang, Wei; Wang, Shixia

    2015-01-01

    The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant and dosing; individual variations among vaccine recipients and 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

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

    DOEpatents

    Gaddy, James L.

    2000-01-01

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

  10. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...) Product Code Number. A number assigned by Animal and Plant Health Inspection Service to each type of..., representing a whole culture or a concentrate thereof, with or without the unevaluated growth products,...

  11. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...) Product Code Number. A number assigned by Animal and Plant Health Inspection Service to each type of..., representing a whole culture or a concentrate thereof, with or without the unevaluated growth products,...

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

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Vecheslav

    Introduction: An anti-radiation vaccine could be an important part of a countermeasures reg-imen for effective radioprotection, immunoprophylaxis and immunotherapy of the acute radi-ation syndromes (ARS) after gamma-irradiation, neutron irradiation or heavy ion irradiation. Reliable protection of non-neoplastic regions of patients with different forms of cancer which undergo to heavy ion therapy ( e.g. Hadron-therapy) can significantly extend the efficiency of the therapeutic course. The protection of cosmonauts astronauts from the heavy ion ra-diation component of space radiation with specific immunoprophylaxis by the anti-radiation vaccine may be an important part of medical management for long term space missions. Meth-ods and experiments: 1. The Antiradiation Vaccine preparation -standard (mixture of toxoid form of Radiation Toxins -SRD-group) which include Cerebrovascular RT Neurotoxin, Car-diovascular RT Neurotoxin, Gastrointestinal RT Neurotoxin, Hematopoietic RT Hematotoxin. Radiation Toxins Specific Radiation Determinant Group were isolated from a central lymph of gamma-irradiated animals with Cerebrovascular, Cardiovascular, Gastrointestiinal, Hematopoi-etic forms of ARS. Devices for γ-radiation are "Panorama", "Puma". 2. Heavy ion exposure was accomplished at Department of Scientific Research Institute of Nuclear Physics, Dubna, Russia. The heavy ions irradiation was generated in heavy ion (Fe56) accelerator -UTI. Heavy Ion linear transfer energy -2000-2600 KeV mkm, 600 MeV U. Absorbed Dose -3820 Rad. 3. Experimental Design: Rabbits from all groups were irradiated by heavy ion accelerator. Group A -control -10 rabbits; Group B -placebo -5 rabbits; Group C -radioprotectant Cystamine (50 mg kg)-5 rabbits, 15 minutes before irradiation -5 rabbits; Group D -radioprotectant Gammafos (Amifostine -400mg kg ), -5 rabbits; Group E -Antiradiation Vaccine: subcuta-neus administration or IM -2 ml of active substance, 14 days before irradiation -5 rabbits. 4

  13. Recombinant influenza vaccines.

    PubMed

    Sedova, E S; Shcherbinin, D N; Migunov, A I; Smirnov, Iu A; Logunov, D Iu; Shmarov, M M; Tsybalova, L M; Naroditskiĭ, B S; Kiselev, O I; Gintsburg, A L

    2012-10-01

    This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery platform for a variety of genetic vaccines. Adenoviruses can efficiently penetrate the human organism through mucosal epithelium, thus providing long-term antigen persistence and induction of the innate immune response. This review provides an overview of the practicability of the production of new recombinant influenza cross-protective vaccines on the basis of adenoviral vectors expressing hemagglutinin genes of different influenza strains. PMID:23346377

  14. 75 FR 47605 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... of which must be a government-issued photo identification such as a Federal employee badge, driver's...; Laboratory of Hepatitis Viruses, and Laboratory of Vector Borne Virus Diseases, Division of Viral...

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

    PubMed Central

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

    2011-01-01

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

  16. Establishment of a standard seed lot system of an Iranian Mumps virus strain; RS-12, for mass production of mumps and MMR vaccines

    PubMed Central

    Shahkarami, M K; Mokhtari Azad, T; Aghaiypour, K; Shafyi, A; Taqavian, M; Mohammadi, A

    2012-01-01

    Background At present the mumps virus strain used for production of mumps vaccine for our local use is Hoshino strain. However, according to our National public health policies, this strain should be replaced with a safer strain. Based on our previous data, the Iranian mumps strain; RS-12 has been proved to be the most suitable alternative to Hoshino strain with little or no adverse events following vaccination Methods The aim of the present study was to optimize propagation of RS-12 strain and prepare standard seeds for vaccine mass production. The virus was inoculated to cells using different methods and different multiplicity of infection (MOI). The viral suspensions were harvested using different methods. Quality control tests were run at different stages. Results Maximum viral yield was achieved when cell suspensions were inoculated at MOI of 1:10 and incubated at 36-37ºC for 48 hours, followed by replacement of the media and incubation at 33-34 ºC for 5-7 days. Filtration did not affect the viral titre. A standard seed lot system was successfully established and experimental batches of MMR vaccines were produced. Conclusion The established seed lot system has met all requirements of WHO regulations and could be used in mass production of safe and efficacious mumps and MMR vaccines. Clinical trials are in progress for this newly produced vaccine. PMID:23115712

  17. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    PubMed

    2003-01-01

    that it should be able to provide these data without conducting further clinical trials. In January 2002, Aviron submitted additional clinical and manufacturing data on FluMist to the US FDA. MedImmune received a second Complete Response Letter from the US FDA on 10 July 2002, requesting clarification and additional data relating to previously submitted information. One of the most significant issues raised by the US FDA was the exacerbated rate of asthma and wheezing in 18-35-month-old patients using FluMist. MedImmune is considering two options to address this issue; to either exclude patients with asthma and wheezing from the label, or to exclude 18- to 30-month-old patients from the proposed indication. On 26 August 2002, MedImmune reported that it had completed the submission of information requested by the US FDA for FluMist. On 17 December 2002, the US FDA's Vaccination and Related Biologicals Products Advisory Committee (VRBPAC) recommended that the FDA approve FluMist to prevent influenza in healthy children, adolescents and adults (ages 5-49 years). Even though the VRBPAC voted in favour of the product's safety in the 50- to 64-year age group, they believed that the data set on efficacy for this age group was insufficient. The committee has also recommended that head-to-head studies should be conducted comparing FluMist to the marketed trivalent inactivated vaccine. Additional clinical trials suggested by the VRBPAC were shedding studies to more clearly define the probability of transmitting the influenza vaccine virus to a high-risk patient and annual revaccination studies. On 30 January 2003, MedImmune announced that it had received a Complete Response Letter from the US FDA requesting clarification and additional information relating to data previously submitted. No additional clinical trials were requested. The company responded to the five questions contained in the letter on 7 February 2003. (ABSTRACT TRUNCATED) PMID:12952502

  18. Valuing vaccination

    PubMed Central

    Bärnighausen, Till; Bloom, David E.; Cafiero-Fonseca, Elizabeth T.; O’Brien, Jennifer Carroll

    2014-01-01

    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. PMID:25136129

  19. Importance of systems biology in engineering microbes for biofuel production

    SciTech Connect

    Mukhopadhyay, Aindrila; Redding, Alyssa M.; Rutherford, Becky J.; Keasling, Jay D.

    2009-12-02

    Microorganisms have been rich sources for natural products, some of which have found use as fuels, commodity chemicals, specialty chemicals, polymers, and drugs, to name a few. The recent interest in production of transportation fuels from renewable resources has catalyzed numerous research endeavors that focus on developing microbial systems for production of such natural products. Eliminating bottlenecks in microbial metabolic pathways and alleviating the stresses due to production of these chemicals are crucial in the generation of robust and efficient production hosts. The use of systems-level studies makes it possible to comprehensively understand the impact of pathway engineering within the context of the entire host metabolism, to diagnose stresses due to product synthesis, and provides the rationale to cost-effectively engineer optimal industrial microorganisms.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Vaccines for allergy

    PubMed Central

    Linhart, Birgit; Valenta, Rudolf

    2012-01-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic. PMID:22521141

  3. Vaccines for allergy.

    PubMed

    Linhart, Birgit; Valenta, Rudolf

    2012-06-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic. PMID:22521141

  4. Regulatory harmonization--a vaccine industry perspective.

    PubMed

    Goodrich, T D

    1997-01-01

    With growth and diversification of aquaculture has come the dissemination of diseases and the increased need to use control measures, both preventative and therapeutic. Preventative measures include good husbandry practices, adequate nutrition and the use of vaccines. Vaccines for aquaculture have generally fallen under the regulatory control of national veterinary medicinal or biological agencies and with that a diverse range of regulatory requirements for authorization and use. More so than any other food animal industry, aquaculture is an international industry with individual entities holding multinational ownership. This situation has created unique problems for the manufacturers of biologicals attempting to service the industry. In recent years, a concerted effort has been made to harmonize regulations to facilitate international trade of vaccines as well as vaccinated animal stocks and their processed food products within and among trading partners. Standardization of requirements for manufacture and testing would ensure national and international interests and consumers of pure, safe and effective products. As the path to harmonization has been slow and not without disagreements, the question remains: What will the standardized requirements be? The manufacturing philosophies of process control (Good Manufacturing Practice) and governmental final product testing for batch release can create a duplicity of effort on the part of the manufacturer that equates to higher economic costs and greater time constraints. The current lack of standardized quality control test methods often means conducting multiple tests to provide the same result. Although efforts are being made to recognize these differences, historical regulations today are based on injectable vaccines for warm-blooded animals. Administration of vaccine products to cold-blooded aquatic species by immersion, bath and oral routes, as well as by injection, creates interpretive problems for manufacturers

  5. Vaccination and consumer perception of seafood quality.

    PubMed

    Engelstad, M

    2005-01-01

    Unlike other segments of international food production, finfish aquaculture has so far not been associated with major food scandals. However, because of increased focus on food safety, the seafood industry and associated businesses have to respond to and document all aspects related to their products and processes. Consumers have a right to know, and need knowledge and information to be able to make qualified choices. In aquaculture good management and environmental attention is essential for both product quality and economic sustainability. One of the main challenges in all farming activities is efficient fish health management, which is crucial for maintaining and further developing the industry. In all biological production, and also in aquaculture, diseases have been, are, and will continue to present a challenge. When dealing with disease incidents, environmental, ethical, biological and economic issues must be taken into account. In animal health management there is a common understanding that prevention is better than treatment, so also in aquaculture. In many segments of industrial fish farming, vaccines have proved a good management tool to control diseases and to reduce both mortality and the use of chemotherapeutics. As seen in a recent Norwegian consumer survey, this might unfortunately look somewhat different from a consumer point of view. The perception of vaccines as foreign substances, visible vaccine lesions or pigment, words about genetically produced vaccines, and a general lack of knowledge may fuel scepticism. Even when experts are giving good and well-documented information, consumers still stick to their original perception of food, including seafood. Given this background, this papers discusses the aquaculture industry's priorities regarding vaccines and vaccination strategies, and its information policy towards the customer. PMID:15962487

  6. Challenges and Opportunities While Developing a Group A Meningococcal Conjugate Vaccine Within a Product Development Partnership: A Manufacturer's Perspective From the Serum Institute of India

    PubMed Central

    Kulkarni, Prasad S.; Socquet, Muriel; Jadhav, Suresh S.; Kapre, Subhash V.; LaForce, F. Marc; Poonawalla, Cyrus S.

    2015-01-01

    Background. In 2002, the Meningitis Vaccine Project (MVP) chose the Serum Institute of India, Ltd (SIIL), as its manufacturing partner to establish a product development partnership (PDP) with the Meningitis Vaccine Project (MVP). MVP was a collaboration between PATH and the World Health Organization (WHO) to develop meningococcal conjugate vaccines for sub-Saharan Africa. Method. From the outset, SIIL recognized that a partnership with MVP carried some risk but also offered important opportunities for accessing new conjugate vaccine technology and know-how. Over 3 years, SIIL successfully accepted technology transfer for the group A meningococcal polysaccharide from SynCo Bio Partners and a conjugation method from the US Food and Drug Administration. Results. SIIL successfully scaled up production of a group A meningococcal conjugate vaccine that used SIIL tetanus toxoid as the carrier protein. Phase 1 studies began in India in 2005, followed by phase 2/3 studies in Africa and India. A regulatory dossier was submitted to the Indian authorities in April 2009 and WHO in September 2009. Export license was granted in December 2009, and WHO prequalification was obtained in June 2010. Vaccine was introduced at public scale in Burkina Faso that December. The group A meningococcal conjugate vaccine was named MenAfriVac, and is the first internationally qualified vaccine developed outside of big pharma. Conclusions. The project proved to be a sound investment for SIIL and is a concrete example of the potential for PDPs to provide needed products for resource-poor countries. PMID:26553678

  7. Production and Evaluation of a Recombinant Chimeric Vaccine against Clostridium botulinum Neurotoxin Types C and D

    PubMed Central

    Gil, Luciana A. F.; da Cunha, Carlos Eduardo P.; Moreira, Gustavo M. S. G.; Salvarani, Felipe M.; Assis, Ronnie A.; Lobato, Francisco Carlos F.; Mendonça, Marcelo; Dellagostin, Odir A.; Conceição, Fabricio R.

    2013-01-01

    Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC) are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB), a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH)3) developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH)3 developed a protective immune response against both BoNT/C (5 IU/mL) and BoNT/D (10 IU/mL), as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH)3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle. PMID:23936080

  8. Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D.

    PubMed

    Gil, Luciana A F; da Cunha, Carlos Eduardo P; Moreira, Gustavo M S G; Salvarani, Felipe M; Assis, Ronnie A; Lobato, Francisco Carlos F; Mendonça, Marcelo; Dellagostin, Odir A; Conceição, Fabricio R

    2013-01-01

    Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC) are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB), a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH)3) developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH)3 developed a protective immune response against both BoNT/C (5 IU/mL) and BoNT/D (10 IU/mL), as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH)3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle. PMID:23936080

  9. Will containment of wild poliovirus in laboratories and inactivated poliovirus vaccine production sites be effective for global certification?

    PubMed Central

    Dowdle, Walter R.; Wolff, Christopher; Sanders, Raymond; Lambert, Scott; Best, Maureen

    2004-01-01

    The absolute laboratory containment of any virus cannot be guaranteed, but a wealth of experience indicates that effective containment of wild poliovirus materials for global certification is technically and operationally feasible. Effective containment is based on the principles of minimal wild poliovirus infectious and potentially infectious materials in laboratories; minimal risks of operations in laboratories and inactivated poliovirus vaccine production facilities; minimal susceptibility of workers to wild poliovirus infection and shedding; and minimal susceptibility of populations to wild poliovirus spread. Each principle alone is imperfect, but collectively they greatly minimize the risks of transmitting wild poliovirus from the laboratory to the community. PMID:15106302

  10. Developing vaccines against pandemic influenza.

    PubMed Central

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illustrated by the production of over 150 million doses of 'swine flu' vaccine in the USA within a 3 month period in 1976. However, there is cause for concern that the lead time to begin vaccine production is likely to be about 7-8 months. Attempts to reduce this time should receive urgent attention. Immunogenicity of vaccines in pandemic situations is compared over the period 1968-1998. A consistent feature of the vaccine trials is the demonstration that one conventional 15 microg haemagglutinin dose of vaccine is not sufficiently immunogenic in naive individuals. Much larger doses or two lower doses are needed to induce satisfactory immunity. There is some evidence that whole-virus vaccines are more immunogenic than split or subunit vaccines, but this needs substantiating by further studies. H5 vaccines appeared to be particularly poor immunogens and there is evidence that an adjuvant may be needed. Prospects for improving the development of pandemic vaccines are discussed. PMID:11779397

  11. Vaccine hesitancy

    PubMed Central

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  12. The chemistry and biology of guanidine natural products.

    PubMed

    Berlinck, Roberto G S; Romminger, Stelamar

    2016-03-01

    Covering: 2012 to 2014. Previous review: Nat. Prod. Rep., 2012, 29, 1382The present review discusses the isolation, structure determination, synthesis, biosynthesis and biological activities of secondary metabolites bearing a guanidine group. Topics include non-ribosomal peptides, alkaloids, guanidine-bearing terpenes, polyketides and shikimic acid derivatives from natural sources. A critical analysis of some yet underdeveloped aspects of guanidine metabolites is also presented. PMID:26689539

  13. Exploitation of biological wastes for the production of value-added products under solid-state fermentation conditions.

    PubMed

    Rodríguez Couto, Susana

    2008-07-01

    Biological wastes contain several reusable substances of high value such as soluble sugars and fibre. Direct disposal of such wastes to soil or landfill causes serious environmental problems. Thus, the development of potential value-added processes for these wastes is highly attractive. These biological wastes can be used as support-substrates in solid-state fermentation (SSF) to produce industrially relevant metabolites with great economical advantage. In addition, it is an environmentally friendly method of waste management. This paper reviews the reutilization of biological wastes for the production of value-added products using the SSF technique. PMID:18543242

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

    NASA Astrophysics Data System (ADS)

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

    2004-09-01

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

  15. Biology Needs a Modern Assessment System for Professional Productivity

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  16. Strategies for optimizing algal biology for enhanced biomass production

    SciTech Connect

    Barry, Amanda N.; Starkenburg, Shawn R.; Sayre, Richard T.

    2015-02-02

    One of the most environmentally sustainable ways to produce high-energy density (oils) feed stocks for the production of liquid transportation fuels is from biomass. Photosynthetic carbon capture combined with biomass combustion (point source) and subsequent carbon capture and sequestration has also been proposed in the intergovernmental panel on climate change report as one of the most effective and economical strategies to remediate atmospheric greenhouse gases. To maximize photosynthetic carbon capture efficiency and energy-return-on-investment, we must develop biomass production systems that achieve the greatest yields with the lowest inputs. Numerous studies have demonstrated that microalgae have among the greatest potentials for biomass production. This is in part due to the fact that all alga cells are photoautotrophic, they have active carbon concentrating mechanisms to increase photosynthetic productivity, and all the biomass is harvestable unlike plants. All photosynthetic organisms, however, convert only a fraction of the solar energy they capture into chemical energy (reduced carbon or biomass). To increase aerial carbon capture rates and biomass productivity, it will be necessary to identify the most robust algal strains and increase their biomass production efficiency often by genetic manipulation. We review recent large-scale efforts to identify the best biomass producing strains and metabolic engineering strategies to improve aerial productivity. In addition, these strategies include optimization of photosynthetic light-harvesting antenna size to increase energy capture and conversion efficiency and the potential development of advanced molecular breeding techniques. To date, these strategies have resulted in up to twofold increases in biomass productivity.

  17. Emerging Vaccine Informatics

    PubMed Central

    He, Yongqun; Rappuoli, Rino; De Groot, Anne S.; Chen, Robert T.

    2010-01-01

    Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning. PMID:21772787

  18. Japanese encephalitis: the virus and vaccines.

    PubMed

    Yun, Sang-Im; Lee, Young-Min

    2014-01-01

    Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV is prevalent in much of Asia and the Western Pacific, with over 4 billion people living at risk of infection. In the absence of antiviral intervention, vaccination is the only strategy to develop long-term sustainable protection against JEV infection. Over the past half-century, a mouse brain-derived inactivated vaccine has been used internationally for active immunization. To date, however, JEV is still a clinically important, emerging, and re-emerging human pathogen of global significance. In recent years, production of the mouse brain-derived vaccine has been discontinued, but 3 new cell culture-derived vaccines are available in various parts of the world. Here we review current aspects of JEV biology, summarize the 4 types of JEV vaccine, and discuss the potential of an infectious JEV cDNA technology for future vaccine development. PMID:24161909

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

    PubMed

    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

  20. 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

  1. Report from the World Health Organization's Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 7-9th Sep 2015.

    PubMed

    Giersing, Birgitte K; Modjarrad, Kayvon; Kaslow, David C; Moorthy, Vasee S

    2016-06-01

    There are more vaccines in development, against a greater number of pathogens, than ever before. A challenge with this exceptional level of activity and investment is how to select and resource the most promising approaches to have the most significant impact on public health. The WHO Product Development for Vaccines Advisory Committee (PDVAC) was established in 2014 to provide strategic advice and recommendations to WHO for vaccines in clinical development that could have a significant impact on public health in low and middle income countries. On 7-9th September 2015, PDVAC was convened for the second time, when the committee reviewed vaccine developments in 24 disease areas. This report summarises the key recommendations from that consultation. PMID:26993336

  2. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... production of biologics. 113.52 Section 113.52 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... Plant Health Inspection Service (APHIS) upon request for performing the tests prescribed in this section... line, such as, but not limited to, microscopic appearance, growth rate, acid production, or...

  3. 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)

  4. 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

  5. Synoptic events force biological productivity in Patagonian fjord ecosystems

    NASA Astrophysics Data System (ADS)

    Daneri, Giovanni

    2016-04-01

    The annual cycle of primary productivity of the Patagonian fjords has, to date, been described as a two phase system consisting of a short non productive winter phase (during June and July) and a productive phase extending from late winter (August) to autumn (May). Low levels of primary production, phytoplankton biomass and high concentrations of surface nutrients have been described as characterizing winter conditions while pulsed productivity events typifies the productivity pattern during the extended productive season. Pulsed productivity events characterize coastal waters where inorganic nutrients in surface layers are replenished following periods of intensive utilization by autotrophs. Freshwater input in Patagonian fjords in southern Chile (41-55°S) results in one of the largest estuarine regions worldwide. Here strong haline water column stratification prevents nutrient mixing to the surface layers thus potentially shutting off algal production. Our working hypothesis considered that in order to reconcile the observed pulsed productivity pattern, periodic breaking (associated to surface nutrient replenishment) and re-establishment of estuarine conditions (associated to water column stratification) would be required. Up to now however our understanding of the physical processes that control water column conditions in the Patagonian fjord area has been extremely limited. Here we present evidence linking the passage of synoptic low pressure fronts to pulsed productivity events in the Patagonian fjord area. These front controls and influence local processes of interaction between the fjord and the atmosphere generating a rapid water column response. In the specific case of the Puyuhuapi fjord we have been able to show that such synoptic fronts induce surface flow reversal and water column mixing. Phytoplankton blooming occurs after the passage of the synoptic front once calmer conditions prevail and estuarine conditions are re established. The occurrence of

  6. 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

  7. Biological carbon monoxide conversion to acetate production by mixed culture.

    PubMed

    Nam, Chul Woo; Jung, Kyung A; Park, Jong Moon

    2016-07-01

    To utilize waste CO for mixed culture gas fermentation, carbon sources (CO, CO2) and pH were optimized in the batch system to find out the center point and boundary of response surface method (RSM) for higher acetate (HAc) production (center points: 25% CO, 40% CO2, and pH 8). The concentrations of CO and CO2, and pH had significant effects on acetate production, but the pH was the most significant on the HAc production. The optimum condition for HAc production in the gas fermentation was 20.81% CO, 41.38% CO2, 37.81% N2, and pH 7.18. The continuous gas fermentation under the optimum condition obtained 1.66g/L of cell DW, 23.6g/L HAc, 3.11g/L propionate, and 3.42g/L ethanol. PMID:27035481

  8. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  9. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  10. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  11. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  12. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  13. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... licensed establishment if he determines that such preparation will not result in contamination of the... precautions which will be taken to prevent contamination of licensed products. Such requests shall...

  14. Strategies for optimizing algal biology for enhanced biomass production

    DOE PAGESBeta

    Barry, Amanda N.; Starkenburg, Shawn R.; Sayre, Richard T.

    2015-02-02

    One of the most environmentally sustainable ways to produce high-energy density (oils) feed stocks for the production of liquid transportation fuels is from biomass. Photosynthetic carbon capture combined with biomass combustion (point source) and subsequent carbon capture and sequestration has also been proposed in the intergovernmental panel on climate change report as one of the most effective and economical strategies to remediate atmospheric greenhouse gases. To maximize photosynthetic carbon capture efficiency and energy-return-on-investment, we must develop biomass production systems that achieve the greatest yields with the lowest inputs. Numerous studies have demonstrated that microalgae have among the greatest potentials formore » biomass production. This is in part due to the fact that all alga cells are photoautotrophic, they have active carbon concentrating mechanisms to increase photosynthetic productivity, and all the biomass is harvestable unlike plants. All photosynthetic organisms, however, convert only a fraction of the solar energy they capture into chemical energy (reduced carbon or biomass). To increase aerial carbon capture rates and biomass productivity, it will be necessary to identify the most robust algal strains and increase their biomass production efficiency often by genetic manipulation. We review recent large-scale efforts to identify the best biomass producing strains and metabolic engineering strategies to improve aerial productivity. In addition, these strategies include optimization of photosynthetic light-harvesting antenna size to increase energy capture and conversion efficiency and the potential development of advanced molecular breeding techniques. To date, these strategies have resulted in up to twofold increases in biomass productivity.« less

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

    SciTech Connect

    Mason, Peter W.; Shustov, Alexandr V.; Frolov, Ilya . E-mail: ivfrolov@utmb.edu

    2006-08-01

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

  16. [Production of a vaccine against enterotoxemia from Clostridium perfringens strains isolated in the field].

    PubMed

    Cherfaoui, S; Kadra, B

    1992-01-01

    We have isolated eight strains of C. perfringens from cases of enterotoxaemia. Five of these strains have revealed themselves toxic with respective types (type "A":2, type "C":2, type "D":1). In order to produce anti-enterotoxaemia vaccine, we have proceeded at the cultivation in fermenter of isolated strains and reference strains CWA 35, CWC and CWD AF. At the end of fermentation, we have evaluated the two following parameters: obtained biomass, and toxin titers. With the two classes of strains we reached an important biomass but toxins titers relatively weak comparatively to that which is usually required. It will be necessary then, to demonstrate the immunogen value of the produced vaccines by testing their efficacity. PMID:1309137

  17. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... live organisms. Safeguards as herein provided shall be established by the research investigator or research sponsor to control disposition of all animals administered experimental biological products or... Regulations). (c) Except as otherwise provided in this paragraph, the research investigator or...

  18. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... live organisms. Safeguards as herein provided shall be established by the research investigator or research sponsor to control disposition of all animals administered experimental biological products or... Regulations). (c) Except as otherwise provided in this paragraph, the research investigator or...

  19. Recommendation for the use of newly introduced Tdap vaccine in Korea

    PubMed Central

    Kim, Kyung Hyo; Kim, Yae-Jean; Kim, Jong-Hyun; Park, Su Eun; Lee, Hoan Jong; Eun, Byung Wook; Jo, Dae Sun; Choi, Eun Hwa; Hong, Young Jin

    2011-01-01

    Pertussis is an acute respiratory infection characterized by paroxysmal cough and inspiratory whoop for over 2 weeks. The incidence of pertussis has decreased markedly after the introduction of DTwP/DTaP vaccine, but the incidence of pertussis has increased steadily among young infant and among adolescents and adults in many countries. Td vaccine was used in this age group but the increase in pertussis has lead to the development of a Tdap vaccine. The Tdap vaccine is a Td vaccine with a pertussis vaccine added and is thought to decrease the incidence and transmission of pertussis in the respective age group. In Korea, two products are approved by the KOREA FOOD & DRUG ADMINISTRATION, which are ADACEL™ (Sanofi-Pasteur, Totonto, Ontario, Canada) and BOOSTRIX® (GlaxoSmithKline Biologicals, Rixensart, Belgium) for those aged between 11-64. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society. PMID:21738546

  20. 77 FR 47397 - Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-08

    ... HUMAN SERVICES Food and Drug Administration Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the Food and Drug Administration's Pediatric Subcommittee of the Oncologic... nominations. SUMMARY: The Food and Drug Administration's (FDA) Office of Hematology and Oncology...

  1. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS General Provisions § 310.4 Biologics; products subject to license control. (a) If a drug has an...

  2. Biological Methanol Production by a Type II Methanotroph Methylocystis bryophila.

    PubMed

    Patel, Sanjay K S; Mardina, Primata; Kim, Sang-Yong; Lee, Jung-Kul; Kim, In-Won

    2016-04-28

    Methane (CH₄) is the most abundant component in natural gas. To reduce its harmful environmental effect as a greenhouse gas, CH₄ can be utilized as a low-cost feed for the synthesis of methanol by methanotrophs. In this study, several methanotrophs were examined for their ability to produce methanol from CH₄; including Methylocella silvestris, Methylocystis bryophila, Methyloferula stellata, and Methylomonas methanica. Among these methanotrophs, M. bryophila exhibited the highest methanol production. The optimum process parameters aided in significant enhancement of methanol production up to 4.63 mM. Maximum methanol production was observed at pH 6.8, 30°C, 175 rpm, 100 mM phosphate buffer, 50 mM MgCl₂ as a methanol dehydrogenase inhibitor, 50% CH₄ concentration, 24 h of incubation, and 9 mg of dry cell mass ml(-1) inoculum load, respectively. Optimization of the process parameters, screening of methanol dehydrogenase inhibitors, and supplementation with formate resulted in significant improvements in methanol production using M. bryophila. This report suggests, for the first time, the potential of using M. bryophila for industrial methanol production from CH₄. PMID:26838340

  3. Construction and Production of Foxp3-Fc (IgG) DNA Vaccine/Fusion Protein

    PubMed Central

    Mousavi Niri, Neda; Memarnejadian, Arash; Hadjati, Jamshid; Aghasadeghi, Mohammad Reza; Shokri, Mehdi; Pilehvar-soltanahmadi, Yones; Akbarzadeh, Abolfazl; Zarghami, Nosratollah

    2016-01-01

    Background: It seems that the success of vaccination for cancer immunotherapy such as Dendritic Cell (DC) based cancer vaccine is hindered through a powerful network of immune system suppressive elements in which regulatory T cell is the common factor. Foxp3 transcription factor is the most specific marker of regulatory T cells. In different studies, targeting an immune response against regulatory cells expressing Foxp3 and their removal have been assessed. As these previous studies could not efficiently conquer the suppressive effect of regulatory cells by their partial elimination, an attempt was made to search for constructing more effective vaccines against regulatory T cells by which to improve the effect of combined means of immunotherapy in cancer. In this study, a DNA vaccine and its respective protein were constructed in which Foxp3 fused to Fc(IgG) can be efficiently captured and processed by DC via receptor mediated endocytosis and presented to MHCII and I (cross priming). Methods: DNA construct containing fragment C (Fc) portion of IgG fused to Foxp3 was designed. DNA construct was transfected into HEK cells to investigate its expression through fluorescent microscopy and flow cytometry. Its specific expression was also assessed by western blot. For producing recombinant protein, FOXP3-Fc fusion construct was inserted into pET21a vector and consequently, Escherichia coli (E. coli) strain BL21 was selected as host cells. The expression of recombinant fusion protein was assayed by western blot analysis. Afterward, fusion protein was purified by SDS PAGE reverse staining. Results: The expression analysis of DNA construct by flow cytometry and fluorescent microscopy showed that this construct was successfully expressed in eukaryotic cells. Moreover, the Foxp3-Fc expression was confirmed by SDS-PAGE followed by western blot analysis. Additionally, the presence of fusion protein was shown by specific antibody after purification. Conclusion: Due to successful

  4. Recent advances in biological production of sugar alcohols.

    PubMed

    Park, Yong-Cheol; Oh, Eun Joong; Jo, Jung-Hyun; Jin, Yong-Su; Seo, Jin-Ho

    2016-02-01

    Sugar alcohols, such as xylitol, mannitol, sorbitol, and erythritol are emerging food ingredients that provide similar or better sweetness/sensory properties of sucrose, but are less calorigenic. Also, sugar alcohols can be converted into commodity chemicals through chemical catalysis. Biotechnological production offers the safe and sustainable supply of sugar alcohols from renewable biomass. In contrast to early studies that aimed to produce sugar alcohols with microorganisms capable of producing sugar alcohols naturally, recent studies have focused on rational engineering of metabolic pathways to improve yield and productivity as well as to use inexpensive and abundant substrates. Metabolic engineering strategies to utilize inexpensive substrates, alleviate catabolite repression, reduce byproduct formation, and manipulate redox balances led to enhanced production of sugar alcohols. PMID:26723007

  5. Process development for biological production of butanol from Eastern redcedar.

    PubMed

    Liu, Kan; Atiyeh, Hasan K; Pardo-Planas, Oscar; Ramachandriya, Karthikeyan D; Wilkins, Mark R; Ezeji, Thaddeus C; Ujor, Victor; Tanner, Ralph S

    2015-01-01

    Eastern redcedar is an invasive softwood species in Oklahoma and across grasslands in the Central Plains of the United States and potential feedstock for butanol production. Butanol has higher energy content than ethanol and can be upgraded to jet and diesel fuels. The objective of this study was to develop a process for production of butanol from redcedar. Results showed that Clostridium acetobutylicum ATCC 824 and Clostridium beijerinckii NCIMB 8052 did not grow in fermentation medium with citrate buffer. However, both strains grew in the medium with acetate buffer, resulting in 3-4g/L greater butanol than without acetate. Detoxification of redcedar hydrolyzate was required to increase butanol concentration from 1 to 13g/L. Hydrolyzate was detoxified by activated carbon to remove inhibitors. Fermentations in detoxified redcedar hydrolyzate reached 13g/L butanol and 19g/L total ABE, comparable to glucose control. This shows the potential for redcedar use in butanol production. PMID:25460988

  6. Systems-Level Synthetic Biology for Advanced Biofuel Production

    SciTech Connect

    Ruffing, Anne; Jensen, Travis J.; Strickland, Lucas Marshall; Meserole, Stephen; Tallant, David

    2015-03-01

    Cyanobacteria have been shown to be capable of producing a variety of advanced biofuels; however, product yields remain well below those necessary for large scale production. New genetic tools and high throughput metabolic engineering techniques are needed to optimize cyanobacterial metabolisms for enhanced biofuel production. Towards this goal, this project advances the development of a multiple promoter replacement technique for systems-level optimization of gene expression in a model cyanobacterial host: Synechococcus sp. PCC 7002. To realize this multiple-target approach, key capabilities were developed, including a high throughput detection method for advanced biofuels, enhanced transformation efficiency, and genetic tools for Synechococcus sp. PCC 7002. Moreover, several additional obstacles were identified for realization of this multiple promoter replacement technique. The techniques and tools developed in this project will help to enable future efforts in the advancement of cyanobacterial biofuels.

  7. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.68 Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA...

  8. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and Drugs... BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.68 Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA...

  9. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.68 Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA...

  10. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.68 Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA...

  11. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.68 Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA...

  12. Endotoxin removal and prevention for pre-clinical biologics production.

    PubMed

    Serdakowski London, Anne; Kerins, Brendan; Tschantz, William R; Eisfeld, Jochen; Mackay, Kasey

    2012-12-01

    The removal of endotoxin from protein solutions and its prevention are key to the success of recombinant protein production due to the possible pyogenic response in mammals caused by contaminated samples. In the pre-clinical situation, protein production is often carried out in a non-good manufacturing practice (GMP) setting, utilizing bacterial DNA for transient transfection and non-validated cleaning techniques. Here, we present our findings evaluating various options for endotoxin removal, and propose strategies for endotoxin prevention with emphasis on chromatographic separations, endotoxin-removing membranes and on-column wash strategies. PMID:23081824

  13. Combination biological and microwave treatments of used rubber products

    DOEpatents

    Fliermans, Carl B.; Wicks, George G.

    2002-01-01

    A process and resulting product is provided in which a vulcanized solid particulate, such as vulcanized crumb rubber, has select chemical bonds altered by biotreatment with thermophillic microorganisms selected from natural isolates from hot sulfur springs. Following the biotreatment, microwave radiation is used to further treat the surface and to treat the bulk interior of the crumb rubber. The resulting combined treatments render the treated crumb rubber more suitable for use in new rubber formulations. As a result, larger loading levels and sizes of the treated crumb rubber can be used in new rubber mixtures and good properties obtained from the new recycled products.

  14. 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

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

    PubMed Central

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

    2014-01-01

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

  16. Vaccination against canine leishmaniosis increases the phagocytic activity, nitric oxide production and expression of cell activation/migration molecules in neutrophils and monocytes.

    PubMed

    Moreira, Marcela L; Costa-Pereira, Christiane; Alves, Marina Luiza Rodrigues; Marteleto, Bruno H; Ribeiro, Vitor M; Peruhype-Magalhães, Vanessa; Giunchetti, Rodolfo C; Martins-Filho, Olindo A; Araújo, Márcio S S

    2016-04-15

    Visceral leishmaniasis (VL) is transmitted by phlebotomine sandfly vectors and domestic dogs serve as a reservoir. The elimination of seropositive dogs has been a recommended strategy for managing the disease in Brazil. A protective canine vaccine would be an important tool for controlling the disease, reducing the parasites available to sandfly vectors and, consequently, reducing the number of human VL cases. Leishmune(®) is an anti-canine Leishmaniosis (VL Canine) vaccine produced by Zoetis (Pfizer, Brazil) that was commercially available in Brazil until 2014. The main goal of the present study was to investigate the protective immunological events induced by vaccination with Leishmune(®) in the time frame of one year. Healthy, non-vaccinated dogs and dogs of 1, 6 and 10 months post-vaccination were evaluated. Results showed that Leishmune(®) induced an increase in phagocytic activity of neutrophils and monocytes and also increased NO production. Immunological events were correlated with functional responses, as high levels of IgG and an increase of the receptor Fcγ were detected. Vaccination induced an increased expression of TLR (2, 4, 5, 9), integrin (CD29, CD49f), activation (MHCII) and co-stimulatory (CD80, CD81) molecules by neutrophils and monocytes. Vaccination led to decrease of IL-4 and an increase of IL-8 production by monocytes and higher IFN-γ and IL-17 production by T-cells. The results suggested that Leishmune(®) was able to induce a long-lasting change in immune response, mediated by supportive immunological events that may be participating in protective immunity against CL. PMID:26995719

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

    PubMed Central

    García-Ruiz, Cristina; Sarabia, Francisco

    2014-01-01

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

  18. DISINFECTION BY-PRODUCT CONTROL THROUGH BIOLOGICAL FILTRATION

    EPA Science Inventory

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production.

    PubMed

    Jensen, Kristoffer Jarlov; Fisker, Ane Bærent; Andersen, Andreas; Sartono, Erliyani; Yazdanbakhsh, Maria; Aaby, Peter; Erikstrup, Christian; Benn, Christine Stabell

    2016-02-28

    As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP ≥ 5 mg/l (28 v. 12%; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95% CI 1·44, 10·90) but not in males (GMR 0·44; 95% CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS. PMID:26678511