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1

Biologic Vaccines  

PubMed Central

The threat of new disease pandemics has spurred the development of biologic vaccines, which promise tremendous improvements in global and local health. Several lend themselves to the prevention or treatment of chronic diseases. But the uncertainties of whom to vaccinate raise the question of whether the health care system can make these promising products viable.

ADAMS, KATHERINE T.

2009-01-01

2

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

Federal Register 2010, 2011, 2012, 2013

...open to the public. Name of Committee: Vaccines and Related Biological Products Advisory...selection of strains to be included in the influenza virus vaccine for the 2013- 2014 influenza season. FDA intends to make background...

2013-01-25

3

Vaccine Production  

Microsoft Academic Search

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

Jack Melling

4

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

Microsoft Academic Search

Most biological products, including vaccines, administered by the parenteral route are required to be tested for sterility at the final container and also at various stages during manufacture. The sterility testing method described in the Code of Federal Regulations (21 CFR 610.12) and the United States Pharmacopoeia (USP, Chapter ) is based on the observation of turbidity in liquid culture

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

2011-01-01

5

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

Federal Register 2010, 2011, 2012, 2013

...Cyanamid Company, No. 17. Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed.\\2\\ Diphtheria and Tetanus Toxoids Adsorbed...Toxoid Adsorbed.\\5\\ Diphtheria and Tetanus Toxoids and Pertussis Vaccine...

2010-12-06

6

Systems biology in vaccine design  

PubMed Central

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.

Six, Adrien; Bellier, Bertrand; Thomas-Vaslin, Veronique; Klatzmann, David

2012-01-01

7

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

Federal Register 2010, 2011, 2012, 2013

...12/838,292, filed Jul 16, 2010; entitled ``Influenza DNA Vaccination and Methods of Use Thereof'', by Rao et al (NIAID...reassortment and adaption to humans. This technology describes DNA vaccines against influenza serotypes H5N1, H1N1, H3N2,...

2011-12-21

8

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

Federal Register 2010, 2011, 2012, 2013

...2012, the committee will meet in open session to discuss and make recommendations on the safety and efficacy of a Hepatitis B Vaccine manufactured by Dynavax. FDA intends to make background material available to the public no later than 2...

2012-10-17

9

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience  

PubMed Central

Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

2011-01-01

10

Plant Production of Veterinary Vaccines and Therapeutics  

Microsoft Academic Search

Plant-derived biologicals for use in animal health are becoming an increasingly important target for research into alternative,\\u000a improved methods for disease control. Although there are no commercial products on the market yet, the development and testing\\u000a of oral, plant-based vaccines is now beyond the proof-of-principle stage. Vaccines, such as those developed for porcine transmissible\\u000a gastroenteritis virus, have the potential to

R. W. Hammond; L. G. Nemchinov

11

Report on Biological Warfare Defense Vaccine Research & Development Programs  

NSDL National Science Digital Library

This 190-page .pdf document, dated July 2001 but released online September 7, 2001 by the US Department of Defense (DoD), gives the latest status of biological warfare defense vaccine development. The DoD assembled a panel of experts in the scientific, regulatory, and industrial aspects of vaccine production and in federal procurement to review the topic. They concluded that the scope and complexity of the DoD biological warfare defense vaccine requirements were too great for either the DoD or the pharmaceutical industry to accomplish alone. The first part of this online report is an executive summary from the DoD, followed by the Floyd D. Spence National Defense Authorization Act For Fiscal Year 2001, and finally the independent panel's full report, Department of Defense Acquisition of Vaccine Production, of December 2000. Sections of the dense, 167-page report include financial and personnel resource requirements, policies, findings, and recommendations.

2001-01-01

12

Vaccine Adverse Events  

MedlinePLUS

... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Print this page Share this page ... About the Center for Biologics Evaluation and Research Vaccine Adverse Events The Vaccine Adverse Event Reporting System ( ...

13

Development of Special Biological Products.  

National Technical Information Service (NTIS)

This report covers the following biological research and developments: (a) Rift Valley Fever (RVF) Vaccine Development - RVF vaccine was prepared and tested. Experiments were done and lots tested for residual live virus. Shipments of vaccine were made to ...

J. L. DeMeio D. E. Craig W. J. Thomas C. K. Lee

1980-01-01

14

Development of pandemic influenza vaccine production capacity in Viet Nam.  

PubMed

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

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

2011-07-01

15

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

PubMed Central

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.

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

16

Vaccine production, distribution, access and uptake  

PubMed Central

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

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

2011-01-01

17

Systems Biology of Seasonal Influenza Vaccination in Humans  

PubMed Central

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

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

2011-01-01

18

Translational Research on Vaccines: Influenza as an Example  

Microsoft Academic Search

Influenza vaccine development is reviewed as an example of ongoing translational research, which is moving fundamental advances in biology into useful products. The types of new influenza vaccines span the gamut of modern biology research and include new methods of vaccine production (tissue culture compared with egg-produced vaccine). New vaccines being studied include recombinant proteins, polynucleotide vaccines, conjugate vaccines, peptides,

R B Belshe

2007-01-01

19

FDA 101: Regulating Biological Products  

MedlinePLUS

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

20

Production of glycoprotein vaccines in Escherichia coli  

PubMed Central

Background Conjugate vaccines in which polysaccharide antigens are covalently linked to carrier proteins belong to the most effective and safest vaccines against bacterial pathogens. State-of-the art production of conjugate vaccines using chemical methods is a laborious, multi-step process. In vivo enzymatic coupling using the general glycosylation pathway of Campylobacter jejuni in recombinant Escherichia coli has been suggested as a simpler method for producing conjugate vaccines. In this study we describe the in vivo biosynthesis of two novel conjugate vaccine candidates against Shigella dysenteriae type 1, an important bacterial pathogen causing severe gastro-intestinal disease states mainly in developing countries. Results Two different periplasmic carrier proteins, AcrA from C. jejuni and a toxoid form of Pseudomonas aeruginosa exotoxin were glycosylated with Shigella O antigens in E. coli. Starting from shake flask cultivation in standard complex medium a lab-scale fed-batch process was developed for glycoconjugate production. It was found that efficiency of glycosylation but not carrier protein expression was highly susceptible to the physiological state at induction. After induction glycoconjugates generally appeared later than unglycosylated carrier protein, suggesting that glycosylation was the rate-limiting step for synthesis of conjugate vaccines in E. coli. Glycoconjugate synthesis, in particular expression of oligosaccharyltransferase PglB, strongly inhibited growth of E. coli cells after induction, making it necessary to separate biomass growth and recombinant protein expression phases. With a simple pulse and linear feed strategy and the use of semi-defined glycerol medium, volumetric glycoconjugate yield was increased 30 to 50-fold. Conclusions The presented data demonstrate that glycosylated proteins can be produced in recombinant E. coli at a larger scale. The described methodologies constitute an important step towards cost-effective in vivo production of conjugate vaccines, which in future may be used for combating severe infectious diseases, particularly in developing countries.

2010-01-01

21

Effects of vaccination against bluetongue on milk production and quality in cattle vaccinated with live-attenuated monovalent type 2 vaccine.  

PubMed

The first epidemic of bluetongue (BT) to affect the three regions of Sardinia, Sicily and Calabria (Italy) in 2000 induced high economic losses caused by the disease itself and by the cessation of ruminant movements both within, and out of, the infected areas. In order to reduce virus circulation, and to create a resistant livestock population, the Italian Ministry of Health ruled, in May 2001, that all sheep, cattle, goats and water buffalo, in infected and in neighbouring regions, be vaccinated. The live-attenuated BTV-2 monovalent vaccine produced by Onderstepoort Biological Products in South Africa was to be used. Accordingly, in 2002, 98.6% of the sheep and goats, and 88.1% of the cattle, on Sardinia were vaccinated. Included was the vaccination of >70% of the cattle in the province of Oristano where >18,000 dairy cows in >220 herds are concentrated in the municipality of Arborea (Oristano) and which account for 65-70% of the milk produced in Sardinia. Using data collected at the centralised dairy co-operative since 1999 the quantity and quality of milk produced before vaccination against bluetongue was compared to that produced after vaccination. The following variables were analysed: average milk production/cow/month, monthly average fat content (%), monthly average protein content (%), average monthly somatic cell count and average monthly platelet count. The findings indicate that vaccination against BTV-2 in Sardinian dairy cattle did not impact negatively upon milk quantity nor milk quality. PMID:20422604

Giovannini, A; Conte, A; Panichi, G; Calistri, P; Dessì, M; Foddis, F; Schintu, A; Caporale, V

2004-01-01

22

Adjuvant solution for pandemic influenza vaccine production.  

PubMed

Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu. PMID:23045649

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

2012-10-23

23

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

PubMed

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

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

2005-01-01

24

Anthrax vaccine. Model of a response to the biologic warfare threat.  

PubMed

Anthrax vaccine is being administered to all 2.4 million active duty, reserve, and National Guard troops, as prophylaxis against biologic warfare. The vaccine's effectiveness in this setting may be limited. This article discusses unresolved issues of safety, with an emphasis on the need for careful surveillance of vaccines used by the military, which has sidestepped the commercial process. Also considered are ethical issues related to the development and use of military biologics, as the United States Army advances its Joint Vaccine Acquisition Program, a plan to produce more than ten vaccines specifically for biologic warfare threat, and to administer them to all military servicemembers. PMID:10198799

Nass, M

1999-03-01

25

Influenza Vaccines: From Surveillance Through Production to Protection  

PubMed Central

Influenza is an important contributor to population and individual morbidity and mortality. The current influenza pandemic with novel H1N1 has highlighted the need for health care professionals to better understand the processes involved in creating influenza vaccines, both for pandemic as well as for seasonal influenza. This review presents an overview of influenza-related topics to help meet this need and includes a discussion of the burden of disease, virology, epidemiology, viral surveillance, and vaccine strain selection. We then present an overview of influenza vaccine—related topics, including vaccine production, vaccine efficacy and effectiveness, influenza vaccine misperceptions, and populations that are recommended to receive vaccination. English-language articles in PubMed published between January 1, 1970, and October 7, 2009, were searched using key words human influenza, influenza vaccines, influenza A, and influenza B.

Tosh, Pritish K.; Jacobson, Robert M.; Poland, Gregory A.

2010-01-01

26

Sex-based Biology and the Rational Design of Influenza Vaccination Strategies.  

PubMed

Biological (ie, sex) differences as well as cultural (ie, gender) norms influence the acceptance and efficacy of vaccines for males and females. These differences are often overlooked in the design and implementation of vaccination strategies. Using seasonal and pandemic influenza vaccines, we document profound differences between the sexes in the acceptance, correlates of protection, and adverse reactions following vaccination in both young and older adults. Females develop higher antibody responses, experience more adverse reactions to influenza vaccines, and show greater vaccine efficacy than males. Despite greater vaccine efficacy in females, both young and older females are often less likely to accept influenza vaccines than their male counterparts. Identification of the biological mechanisms, including the hormones and genes, that underlie differential responses to vaccination is necessary. We propose that vaccines should be matched to an individual's biological sex, which could involve systematically tailoring diverse types of FDA-approved influenza vaccines separately for males and females. One goal for vaccines designed to protect against influenza and even other infectious diseases should be to increase the correlates of protection in males and reduce adverse reactions in females in an effort to increase acceptance and vaccine-induced protection in both sexes. PMID:24966191

Klein, Sabra L; Pekosz, Andrew

2014-07-15

27

Plankton Production Biology.  

National Technical Information Service (NTIS)

Mining existing data I have continued to investigate hydrography and nutrients in respect to plankton production in the central and eastern Arabian Sea and on the shelf off India's west coast. Occasionally I have commented on general oceanographic or ecol...

K. Banse

2013-01-01

28

Plankton Production Biology.  

National Technical Information Service (NTIS)

I continue to investigate geographic and seasonal distributions of hydrography and nutrients in respect to plankton production in the central and eastern Arabian Sea including the continental shelf of India west coast. This year I have added the central B...

K. Banse

2013-01-01

29

Microtitration of Rubella Virus in Monovalent Vaccinal Products  

PubMed Central

Background: Potency test for control of rubella vaccine is a significant factor to qualify production line and vaccination program. For this reason, WHO recommends to use the microtitration method by both vaccine companies and control laboratories. Then the study was done to improve this test. Methods: Three rubella virus samples, including an in-house standard, a lot of vaccine and an in-process product, were tittered in cell culture tubes. Then micro titration steps were tested on 96-well microplate using cocultivation of standard rubella vaccine dilutions and RK-13 cell line. After 6–7 days, final reading was done and calculated the titer. Two other samples were assayed with the micromethod. Results: Titer reduction less than 0.5 log was acquired for each sample during frequent tests and between two methods. Conclusion: The procedure was profitable and accurate for potency and identity tests of rubella virus vaccine, on the basis of WHO recommendations.

Esna-Ashari, F; Shafyi, A; Taqavian, M; Mohammadi, A; Sadigh, ZA; Sabiri, GhH; Mirshahreza, H; Hamzehloo, Z; Taleblue, F; Sheikh-Mohammadi, N

2011-01-01

30

Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines.  

PubMed

The development of cell culture systems for virus propagation has led to major advances in virus vaccine development. Primary and diploid cell culture systems are now being replaced by the use of continuous cell lines (CCLs). These substrates are gaining increasing acceptance from regulatory authorities as improved screening technologies remove fears regarding their potential oncogenic properties. The Vero cell line is the most widely accepted CCL by regulatory authorities and has been used for over 30 years for the production of polio and rabies virus vaccines. The recent licensure of a Vero cell-derived live virus vaccine (ACAM2000, smallpox vaccine) has coincided with an explosion in the development of a range of new viral vaccines, ranging from live-attenuated pediatric vaccines against rotavirus infections to inactivated whole-virus vaccines against H5N1 pandemic influenza. These developments have illustrated the value of this cell culture platform in the rapid development of vaccines against a range of virus diseases. PMID:19397417

Barrett, P Noel; Mundt, Wolfgang; Kistner, Otfried; Howard, M Keith

2009-05-01

31

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

Microsoft Academic Search

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

Bruce Y. Lee; Donald S. Burke

2010-01-01

32

Biological safety concepts of genetically modified live bacterial vaccines  

Microsoft Academic Search

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

Joachim Frey

2007-01-01

33

Baculovirus-expressed influenza vaccine. A novel technology for safe and expeditious vaccine production for human use.  

PubMed

Effectiveness of the influenza vaccine in persons with high-risk conditions needs to be improved. In this paper, the authors review various vaccination strategies, including repeated doses of the vaccine or the use of higher hemagglutinin (HA) content vaccines that have been shown to result in improved immunogenicity. A recombinant HA vaccine produced in insect cells using the baculovirus vectors system presents the possibility for safe and expeditious vaccine production. The high purity of the antigen enables administration at much higher doses without a significant increase in side effects in human subjects. An overview of the use of this production system for the development of alternative influenza vaccine targets is also provided, such as neuraminidase and possibly M2. However, the role of M2 may be more appropriate as an adjuvant vaccine in combination with standard HA vaccine supplement and needs further evaluation. The conclusion that the insect cell-baculovirus production technology is a modern solution for rapid viral or parasitic antigen production is made and that this technology is particularly suitable for influenza where annual adjustment of the vaccine is required. In addition, a highly purified recombinant protein vaccine results in an improved influenza vaccine response in those with high-risk medical conditions. PMID:17594180

Safdar, Amar; Cox, Manon M J

2007-07-01

34

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

PubMed

Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development. PMID:17892164

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

2007-08-01

35

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

PubMed

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

He, Yongqun

2014-07-01

36

MMR Vaccine (Measles, Mumps, and Rubella)  

MedlinePLUS

Mumpsvax® Mumps Vaccine ... Biavax® II (as a combination product containing Mumps Vaccine, Rubella Vaccine) ... II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

37

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

PubMed

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host-pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic ?sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host-pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host-pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines. PMID:21651944

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

2011-09-22

38

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

SciTech Connect

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

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

39

Biological safety concepts of genetically modified live bacterial vaccines.  

PubMed

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 includes knowledge of the precise function and genetic location of the genes to be mutated, their genetic stability, potential reversion mechanisms, possible recombination events with dormant genes, gene transfer to other organisms as well as gene acquisition from other organisms by phage transduction, transposition or plasmid transfer and cis- or trans-complementation. For this, GMOs that are constructed with modern techniques of genetic engineering display a significant advantage over random mutagenesis derived live organisms. The selection of suitable GMO candidate strains can be made under in vitro conditions using basic knowledge on molecular mechanisms of pathogenicity of the corresponding bacterial species rather than by in vivo testing of large numbers of random mutants. This leads to a more targeted safety testing on volunteers and to a reduction in the use of animal experimentation. PMID:17239999

Frey, Joachim

2007-07-26

40

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

PubMed

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

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

2014-01-01

41

Production of Incomplete Vi Antibody in Man by Typhoid Vaccine.  

National Technical Information Service (NTIS)

Groups of volunteers who had been injected with typhoid vaccines responded with the production of incomplete as well as complete Vi antibody. The former was demonstrated at least twice as frequently as the latter in almost all groups, and titers of incomp...

S. Gaines J. A. Currie J. G. Tully

1964-01-01

42

Corn as a production system for human and animal vaccines  

Microsoft Academic Search

The synthesis of selected antigens in plants and their oral delivery has great potential for reducing the costs of vaccine production and administration. The application of this technology requires antigen concentrations in final plant material to be uniform to ensure consistent dosing. In addition, antigen levels should be such as to allow the volume of each dose, containing a set

Stephen J Streatfield; Christopher A Brooks; Donna K Barker; Miranda L Poage; Jocelyne M Mayor; Barry J Lamphear; Carol F Drees; Joseph M Jilka; Elizabeth E Hood; John A Howard

2003-01-01

43

Vaccine production in plant systems--an aid to the control of viral diseases in domestic animals: a review.  

PubMed

Plants have been identified as promising expression systems for the commercial production of vaccines because of the possibility of introducing exogenous genes into them, which permits the development of a new generation of biological products called edible vaccines. The advantages of oral vaccines of this new type are that they induce mucosal, humoral, cellular and protective immunity, they are cheaper, easier to store, distribute and administer, they do not require cold chain management, and some species can be stored for long periods of time without any spoilage and may be administered as purified proteins. Owing to these benefits, plant-produced vaccines represent a valuable option for animal health. The aim of this paper is to present a review of plant-produced vaccines against viruses affecting domestic animals. Some aspects of the feasibility of their use and the immune response elicited by such vaccines are also discussed, as the balance between tolerance and immunogenicity is a major concern for the use of plant-based vaccines. PMID:21087920

Loza-Rubio, Elizabeth; Rojas-Anaya, Edith

2010-12-01

44

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

PubMed

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

Lee, Bruce Y; Burke, Donald S

2010-04-01

45

Adenovirus and its Vector for Developing Vaccines Against Biological Warfare Agents.  

National Technical Information Service (NTIS)

This memorandum reviews a new platform for the development of vaccines against biological warfare (BW) agents. The noted platform uses adenovirus as a vector to deliver DNA that encodes for key antigens of BW agents. Once inside the mammalian cell, this a...

Q. Wu

2004-01-01

46

Challenges in manufacturing adenoviral vectors for global vaccine product deployment.  

PubMed

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

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

2014-04-01

47

Vaccinations  

MedlinePLUS

... be fatal despite treatment. Even though some formerly common diseases have now become uncommon, vaccination is still highly ... in a particular area because they protect from diseases most common in that area. "Non-Core" vaccines are reserved ...

48

Electrophilic natural products and their biological targets.  

PubMed

The study of biologically active natural products has resulted in seminal contributions to our understanding of living systems. In the case of electrophilic natural products, the covalent nature of their interaction has largely facilitated the identification of their biological binding partners. In this review, we provide a comprehensive compilation of electrophilic natural products from all major chemical classes together with their biological targets. Covering Michael acceptor systems, ring-strained compounds and other electrophiles, such as esters or carbamates, we highlight representative and instructive examples for over 20 electrophilic moieties. The fruitful cooperation of natural product chemistry, medicinal chemistry and chemical biology has produced a collection of well-studied examples for how electrophilic natural products exert their biological functions that range from antibiotic to antitumor effects. Special emphasis is put on the elucidation of their respective biological targets via activity-based protein profiling, which together with the recent advancements in mass spectrometry has been crucial to the success of the field. The wealth of naturally occurring electrophilic moieties and their chemical complexity enables binding of a large variety of biological targets, such as enzymes of all classes, nonenzymatic proteins, DNA and other cellular compounds. With approximately 30,000 genes in the human genome but only 266 confirmed protein drug targets, the study of biologically active, electrophilic natural products has the potential to provide insights into fundamental biological processes and to greatly aid the discovery of new drug targets. PMID:22504336

Gersch, Malte; Kreuzer, Johannes; Sieber, Stephan A

2012-06-01

49

Vaccination with F-strain Mycoplasma gallisepticum to reduce production losses in layer chickens.  

PubMed

The effect of Mycoplasma gallisepticum (MG) infection or vaccination of Conn. F-strain MG on 45 weeks of egg production was analyzed using production records from 132 flocks of commercial layer hens. The flocks were located in Pennsylvania, and the data were collected for two years. On the average, layers maintained free from infection with MG laid 15.7 more eggs/hen housed than the MG-infected layers; figures were adjusted for layer-strain effect. This adjusted advantage decreased to 8.7 eggs/hen housed when uninfected flocks were compared with vaccinated flocks. Adjusted average production of vaccinated flocks was 7.0 eggs/hens housed more than production of MG-infected flocks. Egg production of four layer strains was observed with respect to vaccination or natural infection with MG. The four strains responded similarly whether vaccinated or infected. Route of vaccination and age of layer at time of vaccination influenced egg production of vaccinated birds. The adjusted average production/hen housed was 4.9 eggs greater for birds vaccinated via drinking water than for birds vaccinated via spray. The adjusted average was 10.3 eggs/hen housed greater for birds vaccinated between 8 and 18 weeks of age than for birds vaccinated after 18 weeks. PMID:7259680

Carpenter, T E; Mallinson, E T; Miller, K F; Gentry, R F; Schwartz, L D

1981-01-01

50

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

PubMed Central

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

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

2014-01-01

51

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

PubMed

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 AdFMD vaccine lot released is similar to a reference vaccine of proven clinical safety and efficacy. PMID:22888605

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

52

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

USGS Publications Warehouse

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.

Anderson, D. P.

1981-01-01

53

Biological agents in cancer therapy: cytokines, monoclonal antibodies and vaccines  

Microsoft Academic Search

Summary Biological approaches to cancer therapy have gone through phases of early excitement and subsequent neglect and ridicule, and have now entered an era of renewed interest. Unlike Coley and his contemporaries a century ago we are using highly purified agents of impressive potency and specificity of action in our current studies. We have come a long way in dissecting

Herbert F. Oettgen

1990-01-01

54

9 CFR 106.1 - Biological products; exemption.  

Code of Federal Regulations, 2010 CFR

... EXEMPTION FOR BIOLOGICAL PRODUCTS USED IN...UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1 Biological products; exemption...Administrator may exempt any biological product from...the supervision or control of the...

2009-01-01

55

9 CFR 106.1 - Biological products; exemption.  

Code of Federal Regulations, 2010 CFR

... EXEMPTION FOR BIOLOGICAL PRODUCTS USED IN...UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1 Biological products; exemption...Administrator may exempt any biological product from...the supervision or control of the...

2010-01-01

56

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

PubMed

The effect of attenuated Histomonas meleagridis on pullets was investigated and the protection of vaccinated adult laying hens against a severe challenge was studied in the same experimental setting. Four groups of 25 pullets were set up at 18 weeks of life and birds in two groups were vaccinated with in vitro-attenuated H. meleagridis. Chickens in two groups (vaccinated and non-vaccinated) were challenged 5 weeks later with virulent histomonads, while the remaining groups were retained until termination of the study 11 weeks post vaccination. Vaccination of pullets did not have any impact on their subsequent performance. Egg production of non-vaccinated but challenged birds dropped significantly (P ? 0.05) between 2 and 4 weeks post challenge (p.c.) to 58.7%, compared with 90% in control chickens. At 4 weeks p.c., the drop in egg production in vaccinated and challenged birds was significantly lower (P=0.02) than in non-protected layers. Pathological changes were found only in challenged birds 2 and 6 weeks p.c. Several non-vaccinated birds showed severe lesions in the caeca with sporadic involvement of the liver and atrophy of the reproductive tract. Vaccination prior to challenge reduced the incidence of pathological findings. For the first time, vaccination of pullets with in vitro-attenuated histomonads could be shown to be an effective and safe prophylactic tool to prevent a severe drop in egg production of commercial layers following experimental infection. PMID:23391185

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

2013-02-01

57

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

PubMed

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

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

2009-01-01

58

Organomercurial removal from vaccine production wastewaters in a supported liquid membrane bioreactor.  

PubMed

Vaccine production effluents are strongly polluted with thiomersal, a highly toxic organomercurial compound, for which there is presently no remediation technology available. This work describes a new remediation process based on the extraction of thiomersal from the wastewater to a biological compartment, where it is degraded by a microbial strain. The selective extraction of thiomersal is achieved by using an ionic liquid immobilized in a porous membrane. In the biological compartment, thiomersal is degraded to metallic mercury, under aerobic conditions, by a Pseudomonas putida strain. The utilization of ionic liquids in supported liquid membranes for thiomersal transport, and the kinetics of thiomersal biodegradation by a Pseudomonas putida strain are presented and discussed. PMID:15296135

Fortunato, R; Afonso, C A M; Crespo, J G; Reis, M A

2003-01-01

59

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

PubMed

Coccidiosis in chickens is a parasitic disease with great economic significance, which has been controlled successfully for decades using mainly anticoccidial products. However, large-scale and long-term use of anticoccidial drugs has led to the worldwide development of resistance against all these drugs. In order to minimize the occurrence of resistance, the rotation of various anticoccidial drugs in single and/or shuttle programmes is used. Unfortunately, this has not solved the anticoccidial resistance problem. Recently, live anticoccidial vaccines have been incorporated into rotation programmes, resulting in an increasing incidence of anticoccidial drug-sensitive Eimeria spp. field isolates, which may ameliorate the efficacy of anticoccidial drugs. Nevertheless, possible upcoming bans restricting the use of anticoccidials as feed additives, consumer concerns on residues and increasing regulations have prompted the quest for alternative coccidiosis control strategies. Although management and biosecurity measures could halt the introduction of Eimeria spp. to a farm, in practice they do not suffice to prevent coccidiosis outbreaks. Phytotherapy, aromatherapy and pre- and probiotics either show conflicting, non-consistent or non-convincing results, and have therefore not been applied at a large scale in the field. So far, live attenuated and non-attenuated anticoccidial vaccines have proved to be the most solid and successful coccidiosis prevention and control strategy. Despite the drawbacks associated with their production and use, their popularity is increasing. If with time, the immunogenicity of subunit vaccines can be improved, they could represent the next generation of highly efficient and low-cost anticoccidial strategies. PMID:22029884

Peek, H W; Landman, W J M

2011-09-01

60

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

PubMed Central

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

Vemula, Sai V.; Mittal, Suresh K.

2010-01-01

61

Scale-up for bulk production of vaccine against meningococcal disease  

Microsoft Academic Search

At the Netherlands Vaccine Institute (NVI) a vaccine against Neisseria meningitidis serogroup B organisms based on different porA subtypes contained in outer membrane vesicles (OMVs) is in advanced stage of development and will be evaluated in clinical trial studies in the near future. In order to meet the expected demand for product, the current biopharmaceutical production process is being scaled-up.

Gino J. E. Baart; Govert de Jong; Marvin Philippi; Klaas van’t Riet; Leo A. van der Pol; E. Coen Beuvery; Johannes Tramper; Dirk E. Martens

2007-01-01

62

Irrigation to Maximize Vaccine Antigen Production in Genetically Modified Tobacco  

Microsoft Academic Search

A protective antigen (PA) gene from Bacillus anthracis Cohn has been inserted into tobacco (Nicotiana tabacum L.) chloroplasts to produce an anthrax vaccine. The PA protein is the primary immu- nogen of human vaccines for anthrax disease. The objective of this study was to determine the optimum soil water content for producing antigen vaccine in tobacco leaves. High leaf antigen

G. Stevens; E. Vories; M. Mulesky; M. Rhine; D. Dunn

2007-01-01

63

Chemistry and biology of selected natural products  

Microsoft Academic Search

Natural products often offer excitement, stimulation, challenges and op- portunities for chemists, biologists and medical investigators. The study of their chemistry, biology and medicine provides, more often than not, rewards imagined and unimagined, and is still a major frontier in organic chemistry. In this article we summa- rize some of our recent work in this area and project ahead to

K. C. Nicolaou; E. A. Theodorakis; C. F. Claiborne

1996-01-01

64

Complete Genome Sequence of Mycobacterium bovis BCG Korea, the Korean Vaccine Strain for Substantial Production  

PubMed Central

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine available against tuberculosis, and the strains used worldwide represent a family of daughter strains with distinct genotypic characteristics. Here, we report the complete genome sequence of M. bovis BCG Korea, the strain that will be actually used in Korea for vaccine production.

Joung, Sun Myung; Jeon, Sung Joo; Lim, Young Ju; Lim, Jong-Sung; Choi, Beom-Soon; Choi, Ik-Young; Yu, Jeong Hee; Na, Kyung-In; Cho, En-Hi; Shin, Sang-Sook; Park, Young Kil; Kim, Chang-Ki; Kim, Hee-Jin

2013-01-01

65

Biological hydrogen production using a membrane bioreactor  

Microsoft Academic Search

A cross-flow membrane was coupled to a che- mostat to create an anaerobic membrane bioreactor (MBR) for biological hydrogen production. The reactor was fed glucose (10,000 mg\\/L) and inoculated with a soil inoculum heat-treated to kill non-spore-forming methanogens. Hy- drogen gas was consistently produced at a concentra- tion of 57-60% in the headspace under all conditions. When operated in chemostat

Sang-Eun Oh; Prabha Iyer; Mary Ann Bruns; Bruce E. Logan

2004-01-01

66

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

PubMed

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)-? 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)-?-, TNF-?- 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

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

2014-07-01

67

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

PubMed Central

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.

Philbin, Victoria Jane; Levy, Ofer

2009-01-01

68

[Production of interleukin-2 in vitro and in vivo in elderly people, vaccinated with live and inactivated flu vaccines separately and combined].  

PubMed

Forty-three elderly individuals were immunized with Russian trivalent live cold-adapted influenza vaccine (LIV) and US trivalent influenza vaccine (IIV) administered separately or in combination. IL-2 production in vitro (in supernatants of cultures of lymphocytes stimulated with homologous viral antigens and PHA) and in vivo (in blood serum) and other factors of specific antiinfluenza immunity were compared. Vaccination of elderly subjects with commercial vaccines induced T-helper immunological memory, which manifests by increased secretion of IL-2 in vitro and in vivo. Simultaneous vaccination with LIV + IIV and revaccination (in 1 month) with LIV was the most effective method stimulating IL-2 production. The levels of IL-2 production in vitro were in good correlation with the secretion of this cytokin in vivo, lymph proliferation, and serum antibody production. No correlation between IL-2 production in vitro and the formation of local immune response (IgA in nasal swabs) was detected. PMID:10695040

Na?khin, A N; Rekstin, A R; Katz, J; Donina, S A; Grigor'eva, E P; Desheva, Iu A; Arden, N; Rudenko, L G; Cox, N

2000-01-01

69

Impact of Severe Weather Conditions on Biological Products  

MedlinePLUS

... e inundaciones Impact of Severe Weather Conditions on Biological Products CBER is providing interested persons with information concerning the storage and use of temperature-sensitive biological products that have been involved in a temporary ...

70

9 CFR 113.3 - Sampling of biological products.  

Code of Federal Regulations, 2010 CFR

...2009-01-01 2009-01-01 false Sampling of biological products. 113.3 ...REQUIREMENTS Applicability § 113.3 Sampling of biological products. Each...shall be selected to test for viable bacteria and fungi. (ii) Viable...

2009-01-01

71

9 CFR 113.3 - Sampling of biological products.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Sampling of biological products. 113.3 ...REQUIREMENTS Applicability § 113.3 Sampling of biological products. Each...shall be selected to test for viable bacteria and fungi. (ii) Viable...

2010-01-01

72

Thermal Effects on Schistosoma mansoni Irradiation-Attenuated Vaccine Production and Administration.  

National Technical Information Service (NTIS)

Studies were conducted on variable thermal conditions for Schistosoma mansoni nonirradiated cercarial penetration and worm burdens and for irradiation-attenuated vaccine production and administration. A broad range of temperatures (20-35 C) yielded no sig...

M. Stek S. M. Sulaiman

1984-01-01

73

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

PubMed Central

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.

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

2014-01-01

74

Vaccine process technology.  

PubMed

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

Josefsberg, Jessica O; Buckland, Barry

2012-06-01

75

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

PubMed Central

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.

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

2009-01-01

76

Cell Biological Characterization of the Malaria Vaccine Candidate Trophozoite Exported Protein 1  

PubMed Central

In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1). In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

Kulangara, Caroline; Luedin, Samuel; Dietz, Olivier; Rusch, Sebastian; Frank, Geraldine; Mueller, Dania; Moser, Mirjam; Kajava, Andrey V.; Corradin, Giampietro; Beck, Hans-Peter; Felger, Ingrid

2012-01-01

77

Two-tiered biological containment strategy for Lactococcus lactis-based vaccine or immunotherapy vectors.  

PubMed

The concept of biological containment was developed as a strategy to prevent environmental dissemination of engineered live vaccine or drug delivery vehicles. A mutation in the gene encoding thymidylate synthase (thyA), a key enzyme in the pyrimidine biosynthetic pathway, has previously been shown to limit growth of L. lactis vectors under restrictive conditions. We hypothesized that further mutations in the pyrimidine biosynthetic pathway might enhance the stability and safety of live L. lactis vectors. We show that a double mutation in the genes encoding ThyA and CTP synthase (PyrG) in L. lactis confers double auxotrophy for both thymidine and cytidine. However, the combination of two mutations failed to enhance the biological containment phenotype of the engineered strain. In the absence of thymine/thymidine, the thyA mutant exhibited a strong bactericidal phenotype. However, creation of the double mutant caused the loss of this phenotype, though survival in the mouse GI tract was enhanced. The implications for biological containment of live L. lactis based delivery vectors are discussed. PMID:24196273

Hanin, Aurelie; Culligan, Eamonn P; Casey, Pat G; Bahey-El-Din, Mohammed; Hill, Colin; Gahan, Cormac Gm

2014-02-01

78

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

PubMed Central

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.

2014-01-01

79

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

NASA Astrophysics Data System (ADS)

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.

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

1999-06-01

80

Redirection of metabolism for biological hydrogen production.  

PubMed

A major route for hydrogen production by purple photosynthetic bacteria is biological nitrogen fixation. Nitrogenases reduce atmospheric nitrogen to ammonia with the concomitant obligate production of molecular hydrogen. However, hydrogen production in the context of nitrogen fixation is a rather inefficient process because about 75% of the reductant consumed by the nitrogenase is used to generate ammonia. In this study we describe a selection strategy to isolate strains of purple photosynthetic bacteria in which hydrogen production is necessary for growth and independent of nitrogen fixation. We obtained four mutant strains of the photosynthetic bacterium Rhodopseudomonas palustris that produce hydrogen constitutively, even in the presence of ammonium, a condition where wild-type cells do not accumulate detectable amounts of hydrogen. Some of these strains produced up to five times more hydrogen than did wild-type cells growing under nitrogen-fixing conditions. Transcriptome analyses of the hydrogen-producing mutant strains revealed that in addition to the nitrogenase genes, 18 other genes are potentially required to produce hydrogen. The mutations that caused constitutive hydrogen production mapped to four different sites in the NifA transcriptional regulator in the four different strains. The strategy presented here can be applied to the large number of diverse species of anoxygenic photosynthetic bacteria that are known to exist in nature to identify strains for which there are fitness incentives to produce hydrogen. PMID:17220249

Rey, Federico E; Heiniger, Erin K; Harwood, Caroline S

2007-03-01

81

Synthetic Biological Approaches to Natural Product Biosynthesis  

PubMed Central

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.

Winter, Jaclyn M; Tang, Yi

2012-01-01

82

Biological hydrogen production: prospects and challenges.  

PubMed

Hydrogen gas provides exceptional value as an energy carrier and industrial feedstock, but currently is produced entirely by reforming fossil fuels. Biological hydrogen production (BioH(2)), which offers the possibility of being renewable and carbon neutral, can be achieved by photosynthesis, fermentation, and microbial electrolysis cells. This review introduces the principles, advantages and challenges of each approach to BioH(2). Photosynthetic BioH(2) is the ultimate renewable source, since it directly uses inexhaustible resources: sunlight energy and electrons from H(2)O. However, it presents major technical challenges, particularly due to oxygen sensitivity. Fermentative BioH(2) offers a high production rate, but poor conversion efficiency from the organic substrate to H(2). The microbial electrolysis cell can achieve high conversion efficiency, but is an emerging technology. PMID:20189666

Lee, Hyung-Sool; Vermaas, Wim F J; Rittmann, Bruce E

2010-05-01

83

The Avian EB66(R) Cell Line, Application to Vaccines, and Therapeutic Protein Production.  

PubMed

Embryonated chicken eggs and primary chicken embryo fibroblasts (CEFs) have been used for decades as a means of manufacturing human and veterinary vaccines. However, these egg and CEF-based production systems are associated with many serious limitations in terms of their regulatory acceptability, production capacity, and supply chain risks. The development of a safer, cheaper, and more efficient cell substrate for vaccine production would represent a significant business advantage for vaccine manufacturers. Building on the exceptional properties of avian embryonic stem cells, Vivalis has created a new cell substrate, the Duck EB66® cell line. This article describes how this cell substrate was derived, the manufacture and qualification of a master cell bank, and the evaluation of the cell substrate for the manufacture of vaccines and human therapeutic proteins. PMID:21502045

Brown, Stephen W; Mehtali, Majid

2010-01-01

84

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

Microsoft Academic Search

The first scientific attempts to control an infectious disease can be attributed to Edward Jenner, who, in 1796 inoculated an 8-year-old boy with cowpox (vaccinia), giving the boy protection against subsequent challenge with virulent smallpox. Thanks to the successful development of vaccines, many major diseases, such as diphtheria, poliomyelitis and measles, are nowadays kept under control, and in the case

Sissela Liljeqvist; Stefan Ståhl

1999-01-01

85

Biological production of ethanol from coal  

SciTech Connect

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.

Not Available

1992-12-01

86

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

PubMed Central

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

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

2013-01-01

87

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

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 anti-Bm86 specific titers in the range of 1:640 to 1:81920. Conclusion The administration of two initial doses of Gavacplus containing 100 ?g of Bm86 antigen to non-immunized cattle under production conditions is sufficient to affect the weight and the reproductive capacity of R. microplus engorging females. According to these results, cattle herds' manipulation and vaccine costs could be potentially reduced with a positive impact on the implementation of integrated control programs against R. microplus.

2010-01-01

88

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

Microsoft Academic Search

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

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

2011-01-01

89

Effect of Echinacea purpurea on antibody production against fowl influenza vaccine  

Microsoft Academic Search

To study, the effect of Echinacea on production of antibody against avian influenza vaccine 100 chickens were divided into 4 groups: A as negative control, B as positive control (received influenza vaccine H9N2 at 8th day of study), C as B in addition to Echinacea at dose of 0.1% of diet for 2 weeks, D as C but Echinacea at

H. Najafzadeh; M. Ghorbanpour; M. Mayahi; H. Gavzan

2011-01-01

90

New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents.  

PubMed

Although malignant mesothelioma is not a classically immunogenic cancer, there is abundant evidence for immune recognition. The relative ease of obtaining tumor tissue makes mesothelioma ideal for studying surrogate biomarkers such as lymphocytic infiltration or expression of transduced genes. There is evidence that malignant mesothelioma patients as well as asbestos-exposed persons without mesothelioma have impaired immune responsiveness. Substantial progress has been made in animal models using several biological and immunological techniques, but clinical application has been problematic. Systems studied have included lysis by interleukin-2 (IL-2)-activated lymphokine-activated killer (LAK) cells, tumor necrosis factor-alpha (TNF-alpha), a p16-expressing adenovirus vector, suicide gene therapy using the herpes simplex virus-tyrosine kinase (HSV-tk) followed by ganciclovir, and immunomodulatory gene therapy with IL-2, IL-4, interferon-gamma (IFN-gamma), IFN-alpha, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and IL-1beta transfected into tumors. Vaccinia virus has been studied as a vector for cytokine gene transfer. Suicide gene therapy has been combined with a tumor vaccine. The University of Western Australia is initiating a pilot study of autologous vaccination in malignant mesothelioma. Novel agents under study include the angiogenesis inhibitors SU5416, bevacizumab, and thalidomide. ZD1839, an orally administered, highly selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, is being tested in a phase II trial. Since platelet-derived growth factor (PDGF) is thought to be an autocrine growth factor for mesothelioma STI-571 (Gleevec; Novartis, Basel, Switzerland), a highly selective inhibitor of the PDGF receptor tyrosine kinase, is being tested in a phase II trial. The development of more active cytotoxic combinations in this disease should facilitate further studies of chemoimmunotherapy. It seems likely that no single treatment modality will be effective by itself. PMID:11836673

Nowak, Anna K; Lake, Richard A; Kindler, Hedy Lee; Robinson, Bruce W S

2002-02-01

91

Vaccinutveckling inom Foersvaret: Till Gagn foer det Civila Samhaellet (Development of Vaccines by the Defense Which Benefits the Entire Society).  

National Technical Information Service (NTIS)

The document is a brief survey of the proposed Vaccines for Peace, which has become the Bisenthal Vaccine Initiative. Appendices include: (1) Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and ...

G. Sandstroem

1993-01-01

92

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

PubMed

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

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

2008-12-01

93

Recent advances in biological production of 3-hydroxypropionic acid.  

PubMed

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

Kumar, Vinod; Ashok, Somasundar; Park, Sunghoon

2013-11-01

94

[Adverse reactions to vaccines].  

PubMed

Adverse reactions to vaccines are highly varied, ranging from mild local reactions to fatal outcomes. In the last few years many adverse reactions have been attributed to vaccines, often without justification. In agreement with the World Health Organization, these reactions can be classified as follows, depending on the cause: vaccination-induced reactions (due to an effect of the vaccine itself or to an idiosyncrasy); reactions due to errors in storage, manipulation and/or administration; and coincidental reactions (no causal relationship with the vaccine). Hypersensitivity reactions fall into six categories, depending on the causative agent: reactions due to some component of the infectious agent or one of its products; reactions due to adjuvants: aluminium hydroxide; reactions due to stabilizers: gelatin; reactions due to preservatives: thiomersal; reactions due to antibiotics: neomycin; and reactions due to a biological culture medium: chicken embryo cells. Allergic children should not be excluded from the normal vaccine calendar. Immunologically, allergic individuals are more susceptible to infection and to microbial and viral diseases, which often play an aggravating role. Rubella, whooping cough, and influenza usually exacerbate respiratory allergies. Non-vaccination carries a marked risk of contracting serious diseases such as poliomyelitis, tetanus, and diphtheria, etc. In a not too distant future, the techniques of genetic recombination and monoclonal antibody production will allow the creation of vaccines from organisms that cannot be cultivated in the laboratory or that produce small quantities of antigen. These techniques will also lead to identification of the antigens with the greatest immunogenic power and, consequently, to extremely pure vaccines. The adverse reactions to vaccines referred to our service account for between 0.59 % and 1.27 % of first visits in the last three years. We recorded a total of 48 adverse reactions to vaccines. Of these, 44 were attributed to the tetanus vaccine (92 %), 2 to the measles-mumps-rubella vaccine (4 %) and 2 to the meningitis A and C vaccine (4 %). Clinical features consisted of urticaria (11 cases), urticaria with angioedema (7 cases), pseudo-shock (5 cases), fever and urticaria (4 cases), local reactions (4 cases), persistent crying with exanthema (3 cases), giant local reactions with angioedema of the limb (3 cases), anaphylaxis (3 cases), fever > 39.5 C (2 cases), bronchospasm (1 case), and severe atopic dermatitis (1 case).A regimen of hyposensitization to tetanus toxoid was required in 20 patients (45 %); in three, this could not be completed due to generalized urticaria but all the patients presented protective titers with diluted vaccine. PMID:12783762

Eseverri, J L; Ranea, S; Marin, A

2003-01-01

95

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

PubMed

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

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

2009-11-27

96

Inflexal ®V a trivalent virosome subunit influenza vaccine: production  

Microsoft Academic Search

Inflexal®V, a novel virosome-based trivalent influenza vaccine, has been shown to be highly immunogenic and well tolerated in children, young adults, and the elderly. Here we discuss the techniques for the manufacture of Inflexal®V, highlighting the purity and consistency of the manufacturing process. Key factors to be taken into account in the construction of Inflexal®V are the retention of the

Robert Mischler; Ian C Metcalfe

2002-01-01

97

Biological hydrogen production using a membrane bioreactor.  

PubMed

A cross-flow membrane was coupled to a chemostat to create an anaerobic membrane bioreactor (MBR) for biological hydrogen production. The reactor was fed glucose (10,000 mg/L) and inoculated with a soil inoculum heat-treated to kill non-spore-forming methanogens. Hydrogen gas was consistently produced at a concentration of 57-60% in the headspace under all conditions. When operated in chemostat mode (no flow through the membrane) at a hydraulic retention time (HRT) of 3.3 h, 90% of the glucose was removed, producing 2200 mg/L of cells and 500 mL/h of biogas. When operated in MBR mode, the solids retention time (SRT) was increased to SRT = 12 h producing a solids concentration in the reactor of 5800 mg/L. This SRT increased the overall glucose utilization (98%), the biogas production rate (640 mL/h), and the conversion efficiency of glucose-to-hydrogen from 22% (no MBR) to 25% (based on a maximum of 4 mol-H(2)/mol-glucose). When the SRT was increased from 5 h to 48 h, glucose utilization (99%) and biomass concentrations (8,800 +/- 600 mg/L) both increased. However, the biogas production decreased (310 +/- 40 mL/h) and the glucose-to-hydrogen conversion efficiency decreased from 37 +/- 4% to 18 +/- 3%. Sustained permeate flows through the membrane were in the range of 57 to 60 L/m(2) h for three different membrane pore sizes (0.3, 0.5, and 0.8 microm). Most (93.7% to 99.3%) of the membrane resistance was due to internal fouling and the reversible cake resistance, and not the membrane itself. Regular backpulsing was essential for maintaining permeate flux through the membrane. Analysis of DNA sequences using ribosomal intergenic spacer analysis indicated bacteria were most closely related to members of Clostridiaceae and Flexibacteraceae, including Clostridium acidisoli CAC237756 (97%), Linmingia china AF481148 (97%), and Cytophaga sp. MDA2507 AF238333 (99%). No PCR amplification of 16s rRNA genes was obtained when archaea-specific primers were used. PMID:15211496

Oh, Sang-Eun; Iyer, Prabha; Bruns, Mary Ann; Logan, Bruce E

2004-07-01

98

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

PubMed

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

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

2013-12-01

99

9 CFR 103.3 - Shipment of experimental biological products.  

...provided in this section, no person shall ship or deliver for shipment in or from...may be authorized by the Administrator to ship unlicensed biological products for the...Administrator. A request for authorization to ship an unlicensed biological product for...

2014-01-01

100

[Use of continuous human and animal cell lines for the production of viral vaccines].  

PubMed

History of development of safety criteria for continuous human and animal cell lines approved for manufacture of immunobiologic preparations. It was noted that current WHO documents recommend mandatory use of respective WHO's reference cell cultures (Vero-10-87 for continuous cell lines, and Wi-38 or MRC-5 for diploid cell lines) during attestation of new cell cultures proposed for the manufacturing of immunobiologic preparations. Examples of practical use of continuous cell lines (CCLs) for production of viral vaccines on industrial scale are described. On the basis of modern data most important principles were formulated which should be considered to provide safety and efficacy of vaccines produced on the CCLs. PMID:18368760

Grachev, V P; Khapchaev, Iu Kh

2008-01-01

101

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

PubMed

Guidelines issued by regulatory agencies for the development of plant-made pharmaceutical (PMP) products provide criteria for product manufacturing and characterization, safety determination, containment and mitigation of environmental risks. Features of plant-made products do not always enable an easy fit within the criteria subscribed to by regulators. The unconventional nature of plant-based manufacturing processes and peculiarities of plant biology relative to that of traditional biological production systems have led to special considerations in the regulatory scrutiny of PMP. Presented in this review are case studies of two plant-made autologous (patient-specific) cancer vaccines, the nature of which introduced challenges to conventional and standardized development and preclinical evaluation routes. The rationale presented to FDA by the sponsors of each vaccine to build consensus and obtain variances to existing guidelines is discussed. While development of many plant-made biologics can be accomplished within the existing regulatory framework, the development of specialized products can be defended with rational arguments based on strong science. PMID:21358286

Tusé, Daniel

2011-03-01

102

Rabies virus inactivation by binary ethylenimine: new method for inactivated vaccine production.  

PubMed

The inactivation dynamics of rabies virus (PV strain) by binary ethylenimine, and the immunogenic properites and the stability of the vaccines prepared using this agent, were studied. Binary ethylenimine at a final concentration of 0.01 M was prepared wtih 2-bromoethylamine hydrobromide in alkaline solutions, either separately from or in suspensions of rabies virus propagated in BHK cells. The infectivity of virus suspensions containing more than 108 plaque-forming units per 0.1 ml was inactivated in 2 h when the inactivating agent was prepared before its addition to the suspensions, and in3 h when prepared directly in the suspensions. Liquid vaccines prepared in this manner and stored at different temperatures maintained potency for 1 month at 37 degrees C and for 6 months at 4 degrees C and 22 to 25 degrees C. Lyophilized vaccine maintained its potency for 6 months at the three temperatures. The inactivated vaccine mixed with aluminum or oil adjuvant at high dilutions protected guinea pigs against challenge. This safer procedure for rabies virus inactivation offers promise for the production of effective vaccines for the immunization of dogs and cattle. PMID:7358836

Larghi, O P; Nebel, A E

1980-02-01

103

IMMUNOLOGY AND MOLECULAR BIOLOGY Immune Response to a Mucosally Administered Aflatoxin B1 Vaccine  

Microsoft Academic Search

In the present study, a mucosal vaccine was used in an effort to elicit serum IgG and intestinal secretory IgA against the mycotoxin aflatoxin B1 (AFB) in chickens. AFB was coupled to carrier proteins (BSA and porcine thyroglobulin) for use as a vaccine and ELISA coating antigen, respectively. Seven-day-old broiler chicks were divided into groups of 10 and immunized with

J. Wilkinson; D. Rood; D. Minior; K. Guillard; M. Darre; L. K. Silbart

104

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

Code of Federal Regulations, 2010 CFR

...14 Reporting of biological product deviations...manufacturer who holds the biological product license and who had control over the product...should report a biological product deviation...step under your control, acquire...

2009-04-01

105

Effect of a trivalent vaccine against Staphylococcus aureus mastitis lymphocyte subpopulations, antibody production, and neutrophil phagocytosis.  

PubMed

The effect of a novel bovine mastitis trivalent vaccine, containing Staphylococcus aureus capsular polysaccharide type 5 (T5), 8 (T8), and 336 (T336), on lymphocyte subpopulations, antibody production, and neutrophil phagocytosis was evaluated. Twenty pregnant heifers were immunized with either the trivalent alone, trivalent emulsified in Freund's incomplete adjuvant (FICA), trivalent in aluminum hydroxide, or adjuvant only (FICA). Immunization was done 30 d before the expected calving date followed by 2 boosts in a 2-week interval. Compared to FICA, serum antigen-specific immunoglobulin (Ig)G1 and IgG2 were significantly increased in all the vaccinated groups before parturition and sustained until 3 wk postpartum. In comparison with the trivalent alone, formulation with either adjuvant enhanced production of IgG2, but not IgG1. Immune sera, which contained the highest amount of antibodies, slightly increased neutrophil phagocytosis to the 3 serotypes of killed S. aureus, but most of the differences were not significant due to large variation between the cows. The percentage of CD4+ lymphocyte was significantly higher in vaccinated groups than that of FICA 4 wk after the primary immunization. In comparison with FICA, cows inoculated with trivalent vaccine and adjuvants had an increased percentage of CD8+ lymphocytes at 2 time points, 2 wk before and after calving. Our results indicated that the whole cell trivalent vaccine, with or without adjuvants, is able to elicit antibody responses specific to the 3 capsular polysaccharide antigens. The increase of T8-specific IgG2 was more noticeable when the vaccine was emulsified with adjuvants. PMID:15745217

Lee, Jai-Wei; O'Brien, Celia N; Guidry, Albert J; Paape, Max J; Shafer-Weaver, Kimberley A; Zhao, X

2005-01-01

106

Effect of a trivalent vaccine against Staphylococcus aureus mastitis lymphocyte subpopulations, antibody production, and neutrophil phagocytosis  

PubMed Central

Abstract The effect of a novel bovine mastitis trivalent vaccine, containing Staphylococcus aureus capsular polysaccharide type 5 (T5), 8 (T8), and 336 (T336), on lymphocyte subpopulations, antibody production, and neutrophil phagocytosis was evaluated. Twenty pregnant heifers were immunized with either the trivalent alone, trivalent emulsified in Freund’s incomplete adjuvant (FICA), trivalent in aluminum hydroxide, or adjuvant only (FICA). Immunization was done 30 d before the expected calving date followed by 2 boosts in a 2-week interval. Compared to FICA, serum antigen-specific immunoglobulin (Ig)G1 and IgG2 were significantly increased in all the vaccinated groups before parturition and sustained until 3 wk postpartum. In comparison with the trivalent alone, formulation with either adjuvant enhanced production of IgG2, but not IgG1. Immune sera, which contained the highest amount of antibodies, slightly increased neutrophil phagocytosis to the 3 serotypes of killed S. aureus, but most of the differences were not significant due to large variation between the cows. The percentage of CD4+ lymphocyte was significantly higher in vaccinated groups than that of FICA 4 wk after the primary immunization. In comparison with FICA, cows inoculated with trivalent vaccine and adjuvants had an increased percentage of CD8+ lymphocytes at 2 time points, 2 wk before and after calving. Our results indicated that the whole cell trivalent vaccine, with or without adjuvants, is able to elicit antibody responses specific to the 3 capsular polysaccharide antigens. The increase of T8-specific IgG2 was more noticeable when the vaccine was emulsified with adjuvants.

2005-01-01

107

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

PubMed Central

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 week. Thus, this novel automation facilitates standardized large-scale productions of HIV pseudoviruses for ongoing and upcoming HIV vaccine trials.

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

2012-01-01

108

Reflections on 35 years of biological SRM production and analyses  

Microsoft Academic Search

Summary  During the author's 39 years with the National Bureau of Standards (NBS)\\/National Institute for Standards and Technology (NIST)\\u000a as an employee, and since then as Guest Researcher, he has been intimately involved with biological Standard Reference Material\\u000a (SRM) production and analyses. His involvement with biological reference materials started with the very first biological\\u000a certified reference material (CRM), the SRM 1571,

D. A. Becker

2006-01-01

109

Egg production, egg weight, eggshell strength, and mortality in three strains of commercial layers vaccinated with F strain Mycoplasma gallisepticum.  

PubMed

Three strains of commercial leghorns vaccinated at 17 to 22 weeks of age with F strain Mycoplasma gallisepticum (MG) were maintained through 117 weeks of age. The three strains differed in both mortality and percent egg production per hen housed; however, the strains did not differ in egg weight (EW), eggshell strength (ESS), or percent daily egg production. Results of this study indicate EW and ESS for F strain MG-vaccinated hens follow patterns previously reported for uninfected layers. Further, mortality may account, in part, for differences in percent egg production per hen housed between strains of F strain MG-vaccinated hens. PMID:4074249

Branton, S L; Deaton, J W

1985-01-01

110

Biological production of ethanol from coal  

SciTech Connect

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.

Not Available

1990-01-01

111

Biological production of ethanol from coal  

SciTech Connect

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.

Not Available

1990-01-01

112

Biological production of ethanol from coal  

SciTech Connect

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.

Not Available

1991-01-01

113

Biological production of ethanol from coal  

SciTech Connect

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.

Not Available

1992-01-01

114

Biological production of ethanol fom coal  

SciTech Connect

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.

Not Available

1992-05-01

115

Biological pretreatment for production of lignocellulosic biofuel.  

PubMed

Lignocellulosic biomass was submitted to a biological pretreatment prior to a catalytic hydroliquefaction in order to produce biofuel. The biodegradation process was conducted over 3 months in a reactor under controlled conditions. During the biodegradation process the organic matter was characterised and its evolution was correlated with physico-chemical parameters. In parallel with the analysis of the lipidic fraction, analytical pyrolysis was used to monitor bacterial activity. The alterations of branched to linear fatty acids ratio and of mono- to diacids ratio were compared when determined by thermochemolysis and observed in the directly extractable lipids. The evolution of the phytol to the corresponding isoprenoic ketone ratio was observed to be dependent on the desorption technique since it decreases using headspace while it increases using pyrolysis. "Humic"/"fulvic acids" ratio, infrared spectroscopy and thermodifferential analysis were used to determine the degree of OM complexification. PMID:22617032

Lemée, L; Kpogbemabou, D; Pinard, L; Beauchet, R; Laduranty, J

2012-08-01

116

Interferon gamma production during bovine respiratory syncytial virus (BRSV) infection is diminished in calves vaccinated with formalin-inactivated BRSV  

Microsoft Academic Search

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has been associated with severe disease in humans. Research in mice suggests that FI-RSV may prime for decreased interferon gamma (IFN-?) production at subsequent infection. Interferon-? production by peripheral blood mononuclear cells (PBMC) was measured following challenge of calves vaccinated with FI-BRSV to determine whether a similar mechanism is operative in a host naturally

Amelia R. Woolums; Randall S. Singer; Gabrielle A. Boyle; Laurel J. Gershwin

1999-01-01

117

Packet vaccine: black-box exploit detection and signature generation  

Microsoft Academic Search

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

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

2006-01-01

118

The effects of ts-11 strain Mycoplasma gallisepticum vaccination in commercial layers on egg production and selected egg quality parameters.  

PubMed

Live Mycoplasma gallisepticum (MG) vaccines have been USDA approved and licensed for use in commercial layer chickens since 1988; however, egg production and egg quality data exist only for the F strain of MG. Information pertinent to the effects of ts-11 MG on egg and eggshell quality parameters, as well as egg size distribution, is lacking. In this study, pullets were inoculated at 10 wk of age with ts-11 strain MG and placed in biological isolation units at 10 birds/unit. Hen-day egg production, eggshell strength, Haugh unit score, pimpling incidence, and blood/meat spot incidence were monitored and recorded in each trial through a 45-wk production cycle. Further, eggs from all treatments were collected daily, Monday-Thursday, and individually weighed. Results of this study indicate that no significant difference was observed between the treatments for the parameters measured or for egg size distribution. Therefore, these data should lessen producers' concerns pertaining to the impact of ts-11 strain MG on egg production, egg and eggshell quality parameters, and egg size distribution. PMID:11007009

Branton, S L; Lott, B D; May, J D; Maslin, W R; Pharr, G T; Bearson, S D; Collier, S D; Boykin, D L

2000-01-01

119

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

Microsoft Academic Search

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

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

2011-01-01

120

Current biodefense vaccine programs and challenges.  

PubMed

The Defense Threat Reduction Agency's Joint Science and Technology Office manages the Chemical and Biological Defense Program's Science and Technology portfolio. The Joint Science and Technology Office's mission is to invest in transformational ideas, innovative people and actionable technology development for Chemical and Biological Defense solutions, with the primary goal to deliver Science and Technology products and capabilities to the warfighter and civilian population that outpace the threat. This commentary focuses on one thrust area within this mission: the Vaccine program of the Joint Science and Technology Office's Translational Medical Division. Here, we will describe candidate vaccines currently in the S&T pipeline, enabling technologies that should facilitate advanced development of these candidates into FDA licensed vaccines, and how the ever-changing biological threat landscape impacts the future of biodefense vaccines. PMID:23428906

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

2013-07-01

121

Antibodies Elicited by Inactivated Propionibacterium acnes-Based Vaccines Exert Protective Immunity and Attenuate the IL-8 Production in Human Sebocytes: Relevance to Therapy for Acne Vulgaris  

PubMed Central

Propionibacterium acnes is a key pathogen involved in the progression of inflammation in acne vulgaris. We examined whether vaccination against P. acnes suppressed P. acnes-induced skin inflammation. Inactivation of P. acnes with heat was employed to create a P. acnes-based vaccine. Intranasal immunization in mice with this inactivated vaccine provoked specific antibodies against P. acnes. Most notably, immunization with inactivated vaccines generated in vivo protective immunity against P. acnes challenge and facilitated the resolution of ear inflammation in mice. In addition, antibodies elicited by inactivated vaccines effectively neutralized the cytotoxicity of P. acnes and attenuated the production of proinflammatory cytokine IL-8 in human sebocyte SZ95 cells. Intranasal immunization using heat-inactivated P. acnes-based vaccines provided a simple modality to develop acne vaccines. These observations highlight the concept that development of vaccines targeting microbial products may represent an alternative strategy to conventional antibiotic therapy.

Nakatsuji, Teruaki; Liu, Yu-Tsueng; Huang, Cheng-Po; Gallo, Richard L.; Huang, Chun-Ming

2011-01-01

122

Vaccination with cell immunoglobulin mucin-1 antibodies and inactivated influenza enhances vaccine-specific lymphocyte proliferation, interferon-gamma production and cross-strain reactivity.  

PubMed

Influenza virus causes a contagious and potentially serious infection of the upper respiratory tract. While neutralizing antibodies are protective against infection, the problem of antigenic drift remains, requiring the constant monitoring and development of new vaccines. The magnitude of this situation is underscored by the emergence of new potentially human pathogenic influenza strains, avian H5N1 being the most recent example. We present evidence that antibodies against T cell immunoglobulin mucin-1 (TIM-1), a recently identified immunomodulatory molecule, stimulate cellular immunity against influenza viruses and cross-strain immune reactivity. To determine potential immunostimulatory properties of anti-TIM-1, mice were vaccinated with inactivated influenza virus in the presence or absence of TIM-1-specific monoclonal antibodies. Development of cellular immunity against both the influenza strain used for immunization and serotypically distinct virus strains was monitored 3 weeks after vaccination by determining antigen-specific lymphocyte proliferation and cytokine production. Results show that TIM-1 antibodies enhance antigen-specific cellular proliferation (P < 0.05) and interferon (IFN)-gamma production (P < 0.01). Using blocking anti-CD4 and CD8 antibodies, it was observed that antigen-specific cellular proliferation is CD4-dependent and that the majority of proliferating cells are CD4+. Finally, vaccination with inactivated influenza virus with TIM-1 antibody results in the significant (P < 0.001) induction of proliferation and IFN-gamma production upon stimulation with one of three serologically distinct strains. TIM-1 antibodies demonstrate an adjuvant effect promoting antigen-specific cellular proliferation and IFN-gamma production, which are important for the promotion of cell-mediated immunity. These results are the first to suggest that TIM-1 antibody may serve as a potent adjuvant in the development of new influenza virus vaccines. PMID:16792682

Soo Hoo, W; Jensen, E R; Saadat, A; Nieto, D; Moss, R B; Carlo, D J; Moll, T

2006-07-01

123

Light-enhanced primary marine aerosol production from biologically productive seawater  

NASA Astrophysics Data System (ADS)

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.

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

124

Simultaneous determination of trace levels of ethylmercury and methylmercury in biological samples and vaccines using sodium tetra( n -propyl)borate as derivatizing agent  

Microsoft Academic Search

Because of increasing awareness of the potential neurotoxicity of even low levels of organomercury compounds, analytical techniques\\u000a are required for determination of low concentrations of ethylmercury (EtHg) and methylmercury (MeHg) in biological samples.\\u000a An accurate and sensitive method has been developed for simultaneous determination of methylmercury and ethylmercury in vaccines\\u000a and biological samples. MeHg and EtHg were isolated by acid

Darija Gibi?ar; Martina Logar; Nuša Horvat; Andreja Marn-Pernat; Rafael Ponikvar; Milena Horvat

2007-01-01

125

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

PubMed

This study was conducted to determine the effect of overlaying (revaccinating) F-strain Mycoplasma gallisepticum at 22 or 45 wk of age on commercial leghorn hens previously vaccinated with 6/85-strain M. gallisepticum at 10 wk of age. The treatment groups included unvaccinated hens (group 1), hens receiving 6/85-strain M. gallisepticum only (group 2), and hens receiving 6/85-strain M. gallisepticum followed by F-strain M. gallisepticum at either 22 (group 3) or 45 (group 4) wk of age. There was no significant effect on egg production or egg size distribution between any of the treatment groups, unlike previous studies looking at F-strain vaccination only. Egg quality parameters, including eggshell strength, Haugh unit score, and blood-meat spot were similar between the different treatment groups. There was a difference in the rate of pimpling at postpeak production for the treatment group receiving F-strain M. gallisepticum at 22 wk of age, consistent with previously published results. This work suggests that hens previously vaccinated with 6/85-strain M. gallisepticum can be safely revaccinated with F-strain M. gallisepticum to increase protection from field strains while ameliorating the adverse effects associated with F-strain M. gallisepticum vaccination in layers post onset of lay. PMID:20181866

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

2010-03-01

126

Biological and immunological characteristics of lipooligosaccharide-based conjugate vaccines for serotype C Moraxella catarrhalis.  

PubMed

Moraxella catarrhalis is an important bacterial cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS), a major surface antigen of this bacterium, is a potential vaccine component against the organism. There are three major LOS serotypes (serotypes A, B, and C) in clinical isolates of M. catarrhalis. Our previous studies demonstrated that serotype A and B LOS-based conjugates were immunogenic in animals and elicited bactericidal antibodies. In this study, LOS from serotype C strain 26404 was isolated, detoxified, and conjugated to tetanus toxoid (TT) or the cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT, dLOS-CRM-1, and dLOS-CRM-2 vaccine candidates. The molar ratios (dLOS/protein) of the resulting conjugates were 47:1, 19:1, and 32:1, respectively, while the weight ratios were 0.94, 0.84 and 1.44, respectively. All conjugates were highly immunogenic in both mouse and rabbit models. Three subcutaneous injections of each conjugate formulated with the Ribi adjuvant elicited >700-fold increases in serum anti-LOS immunoglobulin G levels in mice (5 microg of dLOS) and >2,000-fold increases in rabbits (50 microg of dLOS). The resulting mouse and rabbit antisera showed complement-mediated bactericidal activity against the homologous strain. In addition, a representative rabbit antiserum showed bactericidal activity against 14 of 18 testable strains, and this bactericidal activity could be 100% inhibited by the serotype C or A LOS but only 30% inhibited by the serotype B LOS. These results indicate that the serotype C LOS-based conjugates can be used as vaccine components for further investigation in humans. PMID:17371852

Yu, Shengqing; Gu, Xin-Xing

2007-06-01

127

The Structural Biology of Enzymes Involved in Natural Product Glycosylation  

PubMed Central

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.

Singh, Shanteri; Phillips, George N.

2012-01-01

128

9 CFR 103.3 - Shipment of experimental biological products.  

Code of Federal Regulations, 2010 CFR

...ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...Animal and Plant Health Inspection Service. (f) Data...biological product in meat animals is not likely...concerning each group of meat animals involved prior...commission firm or abattoir. (h) Any...

2010-01-01

129

9 CFR 103.3 - Shipment of experimental biological products.  

Code of Federal Regulations, 2010 CFR

...ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...Animal and Plant Health Inspection Service. (f) Data...biological product in meat animals is not likely...concerning each group of meat animals involved prior...commission firm or abattoir. (h) Any...

2009-01-01

130

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

PubMed

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

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

2003-01-01

131

Rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or modified-live and killed BHV-1 is associated with virus-specific interferon gamma production  

Microsoft Academic Search

The objective of this study was to determine the effect of vaccination with commercially-available multivalent vaccines containing either modified-live (MLV) bovine herpesvirus-1 (BHV-1) (Bovishield®) or MLV plus killed (MLV+K) BHV-1 (Reliant® Plus) on protection against challenge at 5 days after a single vaccination. An additional objective was to determine whether cell-mediated immunity as measured by virus-specific interferon gamma (IFN-?) production

Amelia R Woolums; Leonardo Siger; Scott Johnson; Guillermo Gallo; Jennifer Conlon

2003-01-01

132

Biodegradation of phytosanitary products in biological wastewater treatment.  

PubMed

Agricultural activity generates two types of waste: firstly, biodegradable organic effluents generally treated by biological processes and, secondly, phytosanitary effluents which contain residues of plant protection products. The latter are collected and treated. Current technological solutions are essentially based on concentration or physical-chemical processes. However, recent improvements in the biodegradability of pesticides open the way to the consideration of alternative, biological, treatment using mixed liquor from wastewater plant activated sludge. The feasibility of the biological treatment of viticultural effluents has been evaluated by the application of pesticides to activated sludge. The necessity for selection of a pesticide-resistant biomass has been highlighted. The elimination of the phytosanitary products shows the potential of a resistant biomass in the treatment of pesticides. The aerated biological storage ponds at three wineries, followed by a sand or reed-bed filter, were used for the treatment of the total annual volume of the viticulture effluents and validate the laboratory experiments. The results show that the biological purification of pesticides by activated sludge is possible by allowing approximately 8 days for biomass adaptation. Stability of purification occurs between 20 and 30 days. PMID:22284913

Massot, A; Estève, K; Noilet, P; Méoule, C; Poupot, C; Mietton-Peuchot, M

2012-04-15

133

Microbial Production of Isoprenoids Enabled by Synthetic Biology  

PubMed Central

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.

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

2013-01-01

134

Soluble microbial products from water biological treatment process: a review.  

PubMed

The relationship between soluble microbial products (SMPs) and extracellular polymeric substances is described, and the characteristics of SMPs in the biological wastewater treatment process, including molecular weight distribution, metal-chelating property, biodegradability, biotoxicity, and membrane fouling, are investigated. The SMPs produced by autotrophs are degradable and utilizable for heterotrophs, thereby confirming the biodegradation of SMPs. Soluble microbial product models are designed through three approaches: establishment of SMP kinetic models or combination with Monod equations, incorporation of SMP generation and degradation into the unified theory raised by Laspidou and Rittmann (2002a), and introduction of the concept of SMP into activated sludge models. The effects of process parameters on SMP concentration are elaborated, based on the optimum biological treatment process operating parameters that can effectively minimize SMP production. The progress of SMP research in water biotreatment systems is presented, and suggestions for future studies are made. PMID:24734470

Kang, Jia; Du, Gang; Gao, Xu; Zhao, Bin; Guo, Jinsong

2014-03-01

135

"Light" Tobacco Products Pose Heavy Health Risks  

MedlinePLUS

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

136

Expression of a recombinant gag protein from endogenous avian virus and its use in screening for antibody reactivity in recipients of chick-derived vaccines  

Microsoft Academic Search

Virions incorporating endogenous avian virus (EAV) RNA have been identified in chick-derived biological products, including the vaccines used to protect against measles, mumps, and yellow fever. The presence of EAV in these vaccines raises safety concerns regarding transmission to vaccine recipients. Development of a serologic assay to detect antibodies to EAV required the discovery of a diagnostic EAV antigen and

Jeffrey A Johnson; Althaf Hussain; Walid Heneine

2003-01-01

137

Use of PCR-based assays for the detection of the adventitious agent porcine circovirus type 1 (PCV1) in vaccines, and for confirming the identity of cell substrates and viruses used in vaccine production.  

PubMed

Safety and quality are important issues for vaccines. Whereas reversion to virulence poses a safety risk with live attenuated vaccines, the potential for the presence of adventitious agents is also an issue of vaccine quality. The recent detection or porcine circovirus type 1 (PCV1) in human vaccines has further highlighted the importance of quality control in vaccine production. The purpose of this study was to use a novel conventional PCR to detect PCV1, and subsequently screen materials used in the manufacture of vaccines at Bharat Biotech International Limited, India. The genome or gene fragments of PCV1 were not detected in any of the vaccines and materials tested, including the live attenuated rotavirus vaccine candidate ROTAVAC(®). Further, the identity of the cells and the viruses used as starting materials in the manufacture of these vaccines was confirmed by species-specific PCR or virus-specific RT-PCR, and no cross-contamination was detected in any case. The methods can be applied for regular in-house quality control screening of raw materials and seeds/banks, as well as formulated vaccines. PMID:22079617

Kumar, Deepak; Beach, Nathan M; Meng, Xiang-Jin; Hegde, Nagendra R

2012-01-01

138

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

PubMed

Vero cells are utilized for production of rabies vaccine. This study deals with the optimize quantity media require for the rabies vaccine production in the smooth roller surface. The rabies virus (Pasteur vaccine strain) is infected to monolayer of the various experimented bottles. To analyze the optimal quantity of media for the production of rabies viral harvest during the process of Vero cell derived rabies vaccine. The trials are started from 200 to 400 mL (PTARV-1, PTARV-2, PTARV-3, PTARV-4 and PTARV-5). The samples are taken in an appropriate time intervals for analysis of In Process Quality Control (IPQC) tests. The collected viral harvests are further processed to rabies vaccine in a pilot level and in addition to scale up an industrial level. Based on the evaluation the PTARV-2 (250 mL) show highly encouraging results for the Vero cell derived rabies vaccine production. PMID:20384277

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

2009-09-15

139

Schistosomiasis vaccines  

PubMed Central

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.

Siddiqui, Bilal A.; Ganley-Leal, Lisa

2011-01-01

140

Cancer vaccines.  

PubMed

Cancer vaccines have been extensively tested in animal models, and in humans. Initial studies focused on first generation vaccines based on whole cell preparations or tumor lysates derived from autologous or allogeneic tumors. Clinical studies conducted with such candidate vaccines contributed to establish the feasibility of immunizing cancer patients against their own tumors. Significant clinical benefits were observed, both in terms of long term survival and recurrence rate, in some of these trials. More recently, however, cancer vaccines targeting well-characterized tumor-associated antigens, i.e. molecules selectively or preferentially expressed by cancer cells but not by normal cells, have been designed and tested in humans. Results obtained as of today with these second-generation vaccines suggest that they are safe and that they can elicit humoral and cellular responses against tumor-specific antigens, without inducing unacceptable clinical signs of autoimmunity. Advances in tumor biology and tumor immunity have helped to better understand the mechanisms displayed by a number of tumors to escape host immunity. This bulk of new knowledge will be used to design future cancer vaccines, which will likely target multiple TAAs, presented by different antigen presentation platforms, in association with synthetic adjuvants and/or immunostimulatory cytokines. Lastly, specific tools allowing to assess in a qualitative and quantitative manner immune responses are critically needed in order to establish correlates between clinical and immune responses in patients receiving experimental vaccines. PMID:11163653

Moingeon, P

2001-01-01

141

Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets  

Microsoft Academic Search

To investigate the biological indicator for vaccine efficacy against HPAI H5N1 virus challenge of varying clades, two inactivated whole-virus H5N1 vaccines containing the hemagglutinin (HA) and neuraminidase (NA) genes of either clade 2.2 A\\/EM\\/Korea\\/W149\\/06 (RgKoreaW149\\/06xPR8) or clade 2.5 A\\/Ck\\/Korea\\/ES\\/03 (RgKoreaES223N\\/03XPR8) virus in the background of A\\/PR\\/8\\/34 (H1N1) were generated by reverse genetics. Administration of the vaccines (2-dose 1.77, 3.5, 7.5

Min-Suk Song; Taek-Kyu Oh; Philippe Noriel Q. Pascua; Ho-Jin Moon; Jun Han Lee; Yun Hee Baek; Kyu-Jin Woo; Yeup Yoon; Moon-Hee Sung; Haryoung Poo; Chul-Joong Kim; Young Ki Choi

2009-01-01

142

Tuberculosis vaccine development: recent progress  

Microsoft Academic Search

Recent years have seen a renewed effort to develop new vaccines against tuberculosis. As a result, several promising avenues of research have developed, including the production of recombinant vaccines, auxotrophic vaccines, DNA vaccines and subunit vaccines. In this article we briefly review this work, as well as consider the pros and cons of the animal models needed to test these

Ian M. Orme; David N. McMurray; John T. Belisle

2001-01-01

143

Systems Biology of Recombinant Protein Production in Bacillus megaterium  

NASA Astrophysics Data System (ADS)

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.

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

144

Rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or modified-live and killed BHV-1 is associated with virus-specific interferon gamma production.  

PubMed

The objective of this study was to determine the effect of vaccination with commercially-available multivalent vaccines containing either modified-live (MLV) bovine herpesvirus-1 (BHV-1) (Bovishield) or MLV plus killed (MLV + K) BHV-1 (Reliant Plus) on protection against challenge at 5 days after a single vaccination. An additional objective was to determine whether cell-mediated immunity as measured by virus-specific interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) was associated with any early protection induced by vaccination. Clinical signs, serum neutralizing (SN) titers, and nasal virus isolation (VI) titers were also measured. The 12-16-week-old dairy cross-calves seronegative for antibodies to BHV-1 were vaccinated with a multivalent vaccine containing MLV BHV-1 (n = 19), a multivalent vaccine containing MLV + K BHV-1 (n = 19), or a control multivalent vaccine not containing BHV-1 (n = 10) on day 0 and challenged intranasally on day 5. PBMC were isolated on days 0, 3, 5, 8, 10, 14 and 19. PBMC were incubated in vitro with spent media, live BHV-1, or heat-inactivated BHV-1 for 72 h. Supernatants were assayed for bovine IFN-gamma by ELISA. Bovine herpesvirus-1-specific IFN-gamma production was expressed as percent of the kit positive control, with value for spent media subtracted. Clinical signs were monitored daily. Serum VN titers were measured on days 0-5 and 19. Nasal VI titer was measured every other day from days 5 to 19. Interferon gamma production was higher on day 5, and was significantly increased post-challenge, in both vaccine groups compared to controls. There was no difference between vaccine groups on any day. There was no significant difference in SN titer among groups on any day. Virus isolation titer was significantly higher in controls on days 6 and 8 compared to both vaccine groups. Temperatures were significantly higher and nasal discharge was present more often post-challenge in controls compared to vaccine groups. Vaccination 5 days prior to challenge with commercially-available vaccine containing MLV or MLV + K BHV-1 was associated with increased BHV-1-specific IFN-gamma production, decreased viral shedding, lower temperatures and less nasal discharge post-challenge. Cell mediated immune responses as measured by IFN-gamma production are stimulated rapidly following BHV-1 vaccination of calves. PMID:12559793

Woolums, Amelia R; Siger, Leonardo; Johnson, Scott; Gallo, Guillermo; Conlon, Jennifer

2003-03-01

145

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

NASA Technical Reports Server (NTRS)

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.

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

2007-01-01

146

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

NASA Technical Reports Server (NTRS)

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.

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

2006-01-01

147

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

NASA Astrophysics Data System (ADS)

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.

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

148

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

PubMed Central

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.

Gellert, Akos; Salanki, Katalin; Tombacz, Kata; Tuboly, Tamas; Balazs, Ervin

2012-01-01

149

Interferon gamma production during bovine respiratory syncytial virus (BRSV) infection is diminished in calves vaccinated with formalin-inactivated BRSV.  

PubMed

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has been associated with severe disease in humans. Research in mice suggests that FI-RSV may prime for decreased interferon gamma (IFN-gamma) production at subsequent infection. Interferon-gamma production by peripheral blood mononuclear cells (PBMC) was measured following challenge of calves vaccinated with FI-BRSV to determine whether a similar mechanism is operative in a host naturally susceptible to RSV. Eight-week old male Holstein calves were administered FI-BRSV and mock challenge (V/M, n = 6); mock vaccination and BRSV challenge (M/C, n = 6) or FI-BRSV and BRSV challenge (V/C, n = 7). Vaccine was administered twice at a 2-week interval; challenge followed one month later. On days 0, 5 and 10 postchallenge (PC), PBMC were stimulated in vitro for 24 h with live BRSV, concanavalin A (positive control) or spent media (negative control). Supernatants were assayed for IFN-gamma using ELISA. Interferon-gamma production by BRSV-stimulated PBMC was increased in M/C and V/C calves as compared to V/M calves on day 5 PC (p < 0.015); and increased in M/C calves compared to V/C and V/M calves on day 10 PC (p < 0.015). Over time postchallenge, a significant increase in IFN-gamma production by BRSV-stimulated PBMC was seen in M/C calves (p < 0.025) but not in V/C calves. FI-BRSV vaccination of calves led to diminished IFN-gamma production postchallenge. Decreased IFN-gamma production may have contributed to impaired viral clearance and enhanced disease in FI-BRSV vaccinated calves. PMID:10195762

Woolums, A R; Singer, R S; Boyle, G A; Gershwin, L J

1999-03-17

150

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

Microsoft Academic Search

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

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

2005-01-01

151

Using Polyclonal and Monoclonal Antibodies in Regulatory Testing of Biological Products  

Microsoft Academic Search

Polyclonal and monoclonal antibodies are often used in regulatory testing of biologicals (vaccines and related prod- ucts). One of the most common applications for antibody- based immunoassays is as a batch release test. Batch release tests, whether they measure serological responses to vacci- nation or they quantify individual antigens by in vitro meth- ods, must provide an acceptable estimate of

Nancy E. Coe Clough; Paul J. Hauer

152

Study of Shigella Vaccines in Man.  

National Technical Information Service (NTIS)

Studies have continued to evaluate the safety, biologic properties and efficacy of various oral Shigella vaccine candidates. The most recent vaccine candidates employed have been Escherichia coli bearing Shigella group antigens. These vaccine candidates a...

R. B. Hornick

1974-01-01

153

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

Code of Federal Regulations, 2010 CFR

...submit a list of licensed biological products prepared in the licensed...product or provisions that the biological product is restricted to use...distribution and use of a veterinary biological product be restricted...Management and Budget under control number 0579-0013)...

2009-01-01

154

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

Code of Federal Regulations, 2010 CFR

...submit a list of licensed biological products prepared in the licensed...product or provisions that the biological product is restricted to use...distribution and use of a veterinary biological product be restricted...Management and Budget under control number 0579-0013)...

2010-01-01

155

Developments in the production and quality control of poliovirus vaccines – Historical perspectives  

Microsoft Academic Search

Using virus grown in monkey kidney cells, Salk and his colleagues developed an inactivated poliovirus vaccine (IPV) in 1952. A large-scale field trial showed the vaccine to be safe and highly immunogenic in children, but soon after the vaccine became generally available in 1955, cases of paralytic disease were reported in recipients. Investigations showed that almost all the cases occurred

J. Furesz

2006-01-01

156

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. ...

157

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

PubMed Central

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.

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

1986-01-01

158

Biological treatment of chicken feather waste for improved biogas production.  

PubMed

A two-stage system was developed which combines the biological degradation of keratin-rich waste with the production of biogas. Chicken feather waste was treated biologically with a recombinant Bacillus megaterium strain showing keratinase activity prior to biogas production. Chopped, autoclaved chicken feathers (4%, W/V) were completely degraded, resulting in a yellowish fermentation broth with a level of 0.51 mg/mL soluble proteins after 8 days of cultivation of the recombinant strain. During the subsequent anaerobic batch digestion experiments, methane production of 0.35 Nm3/kg dry feathers (i.e., 0.4 Nm3/kg volatile solids of feathers), corresponding to 80% of the theoretical value on proteins, was achieved from the feather hydrolyzates, independently of the pre-hydrolysis time period of 1, 2 or 8 days. Cultivation with a native keratinase producing strain, Bacillus licheniformis resulted in only 0.25 mg/mL soluble proteins in the feather hydrolyzate, which then was digested achieving a maximum accumulated methane production of 0.31 Nm3/kg dry feathers. Feather hydrolyzates treated with the wild type B. megaterium produced 0.21 Nm3 CH4/kg dry feathers as maximum yield. PMID:22432272

Forgács, Gergely; Alinezhad, Saeid; Mirabdollah, Amir; Feuk-Lagerstedt, Elisabeth; Horváth, Ilona Sárvári

2011-01-01

159

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

Code of Federal Regulations, 2010 CFR

...administered experimental biological products or live organisms...or research sponsor to control disposition of all animals...administered experimental biological products or live organisms...including challenged control animals) shall...

2009-01-01

160

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

Code of Federal Regulations, 2010 CFR

...administered experimental biological products or live organisms...or research sponsor to control disposition of all animals...administered experimental biological products or live organisms...including challenged control animals) shall...

2010-01-01

161

Molecular biology in studies of oceanic primary production  

SciTech Connect

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.

LaRoche, J.; Falkowski, P.G. (Brookhaven National Lab., Upton, NY (United States)); Geider, R. (Delaware Univ., Lewes, DE (United States). Coll. of Marine Studies)

1992-01-01

162

Molecular biology in studies of oceanic primary production  

SciTech Connect

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.

LaRoche, J.; Falkowski, P.G. [Brookhaven National Lab., Upton, NY (United States); Geider, R. [Delaware Univ., Lewes, DE (United States). Coll. of Marine Studies

1992-07-01

163

Minimization of excess sludge production for biological wastewater treatment.  

PubMed

Excess sludge treatment and disposal currently represents a rising challenge for wastewater treatment plants (WWTPs) due to economic, environmental and regulation factors. There is therefore considerable impetus to explore and develop strategies and technologies for reducing excess sludge production in biological wastewater treatment processes. This paper reviews current strategies for reducing sludge production based on these mechanisms: lysis-cryptic growth, uncoupling metabolism, maintenance metabolism, and predation on bacteria. The strategies for sludge reduction should be evaluated and chosen for practical application using costs analysis and assessment of environmental impact. High costs still limit technologies of sludge ozonation-cryptic growth and membrane bioreactor from spreading application in full-scale WWTPs. Bioacclimation and harmful to environment are major bottlenecks for chemical uncoupler in practical application. Sludge reduction induced by oligochaetes may present a cost-effective way for WWTPs if unstable worm growth is solved. Employing any strategy for reducing sludge production may have an impact on microbial community in biological wastewater treatment processes. This impact may influence the sludge characteristics and the quality of effluent. PMID:14511716

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

2003-11-01

164

Comparative evaluation of conventional polymerase chain reaction (PCR), with loop-mediated isothermal amplification and SYBR green I-based real-time PCR for the quantitation of porcine circovirus-1 DNA in contaminated samples destined for vaccine production.  

PubMed

Porcine circovirus type1 (PCV1), described initially as a contaminant of a porcine kidney cell line, is ubiquitous within the swine population The presence of PCV1 in porcine cell lines can lead to contamination during both human and porcine vaccine production. Therefore, a rapid, specific, sensitive and practical method is needed for the detection of PCV1 in bio-products. The aim of this study was to compare three assays in their ability to accurately quantify PCV1 virus in biological samples, namely loop-mediated isothermal amplification (LAMP), SYBR green I-based real-time polymerase chain reaction (PCR) and conventional PCR. All assays yielded successful quantitation of PCV1 DNA and differentiated between PCV1-free and-contaminated cells. In addition, the results were specific for PCV1, since amplification of samples containing closely-related PCV2 or other pathogenic swine viruses yielded negative results. The lowest detection threshold of 10(2) copies was displayed by the SYBR green I-based real-time PCR assay. In addition, this assay was the most effective in detecting PCV1 contamination in a set of commercially available porcine vaccines. Therefore we conclude that SYBR green I-based real-time PCR is specific and sensitive for detecting PCV1 in biological samples and maybe used for quality control of vaccine and biomaterial production. PMID:23538038

Yang, Bo-Chao; Wang, Feng-Xue; Zhang, Shu-Qin; Song, Ni; Li, Jian-Xi; Yang, Zhi-Qiang; Wen, Yong-Jun; Wu, Hua

2013-07-01

165

[Towards a new vaccine economy?].  

PubMed

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

Poirot, P; Martin, J F

1994-01-01

166

Current studies on physiological functions and biological production of lactosucrose.  

PubMed

Lactosucrose (O-?-D-galactopyranosyl-(1,4)-O-?-D-glucopyranosyl-(1,2)-?-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 ?-fructofuranosidase from Arthrobacter sp. K-1 or a range of levansucrases, or through transgalactosylation by ?-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

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

2013-08-01

167

Systems biological approaches towards understanding cellulase production by Trichoderma reesei  

PubMed Central

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.

Kubicek, Christian P.

2013-01-01

168

Current concepts and future approaches to the development of autologous/autogenous vaccines for veterinary use.  

PubMed

Current classification of autologous/autogenous (A/A) vaccines is commonly based on the concept of strain/antigen specificity associated with targeted treatment of a restricted number of animals. However, fulfilling these two conditions is not sufficient for immune-veterinary immunebiologicals to be excluded from the provisions of Directive 2001/82/EC. Indeed, non-inactivated A/A vaccines are not automatically considered out of the scope of the community code relating to veterinary medicinal products, in particular to immune-biologicals. As a major consequence of the "regulatory" exclusion from the requirements of EU rules, A/A vaccines can be usually manufactured and distributed without having obtained a marketing authorization by the competent authority of a Member State. Furthermore, strain specificity enables veterinarians to consider the use of these vaccines in quite a large variety of epidemiological circumstances where no "conventional" vaccines are yet available or are considered efficacious. In addition, in contrast to "conventional" vaccines, which are considered exclusively as a preventive tool against infectious diseases, A/A vaccines can also be used to treat "continuing" infections. Although the limited scientific value of these products and the poor investigations of the effector mechanisms involved are widely recognized, their use is still claimed in conditions where disorders in the immune system are suspected. Today, a more appropriate definition of A/A vaccines is one that takes into account their historical tradition and practical use, such as stable- or herd-specific vaccines, custom ("..ized") vaccines, therapeutic vaccines, pharmavaccines, vaccines used for biological therapy, etc. Although acknowledging the "regulatory autonomy" of A/A vaccines versus "conventional" vaccines, here it will be presented as an overview of the necessary points to consider, to guarantee an acceptable standard in the development and control of this particular category of veterinary immune-biologicals. PMID:15597617

Tollis, M

2004-01-01

169

Female contraceptive vaccine possible, but not for years.  

PubMed

Researchers are presently testing 2 types of contraceptive vaccines in animal models. One of these is the sperm antigen vaccine which would cause immunity to sperm within the female reproductive tract. The other works against the zona pellucida (the extracellular membrane surrounding the ovum) which the sperm must bind to and penetrate for fertilization to take place. At this time, researchers do not yet know what vaccine is the best route. The sperm antigen vaccine would inhibit capacitation--that stage where they become capable of fertilizing the ovum. The researchers foresee certain problems with this vaccine, however. For example, it will be difficult to get a vaccine to work properly within just the reproductive tract since most antigen vaccines work within the entire immune system. Further, all the areas of the reproductive tract are biologically different. In addition, researchers must find a vaccine potent enough to affect the millions of sperm that enter the uterus. A potential problem with the zona pellucida vaccine is that it could create ovarian dysfunction permanently. Therefore, researchers realize the importance of finding a zona pellucida vaccine that will induce fertilization but not destroy the ovaries. WHO is in the early stages of working on a vaccine against human chorionic gonadotropin to prevent implantation, but this and any postfertilization vaccine will probably not be produced for the US market because of the present antiabortion sentiment. Additional barriers to production of a contraceptive vaccine is that pharmaceutical companies fear liability in marketing a new contraceptive and their profit margin will be low. Nevertheless, the earliest a contraceptive vaccine would become available in 1999. PMID:12342587

1989-10-01

170

Polysaccharide-Based Vaccines  

NASA Astrophysics Data System (ADS)

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.

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

171

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

NASA Technical Reports Server (NTRS)

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

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

1994-01-01

172

First self-adjuvant multicomponent potential vaccine candidates by tethering of four or eight MUC1 antigenic immunodominant PDTRP units on a calixarene platform: synthesis and biological evaluation.  

PubMed

MUC1 protein overexpressed in human epithelial carcinoma is a target in development of novel anticancer vaccines. Multiple units of immunodominant B-cell epitope PDTRP MUC1 core sequence were conjugated to calix[4,8]arene platforms containing TLR2 ligand, to produce two novel anticancer self-adjuvant vaccine candidates. The immunogenicity of the synthetic constructs was investigated by immunization of mice in vivo. ELISA assay evidenced that the vaccine candidates stimulate anti MUC1 IgG antibody production (major for the octavalent construct) and no additive effect but a multivalency effect was observed when compared to an analogous monovalent. Octa- and tetravalent constructs lacking in PDTRP peptide moieties did not show anti MUC1 IgG antibody production in mice. The antibodies induced by the synthesized constructs are able to recognize the MUC1 structures present on MCF7 tumor cells. The results display that calixarenes are convenient platforms for building multicomponent self-adjuvant vaccine constructs promising as immunotherapeutic anticancer agents. PMID:24041198

Geraci, Corrada; Consoli, Grazia M L; Granata, Giuseppe; Galante, Eva; Palmigiano, Angelo; Pappalardo, Maria; Di Puma, Salvatore D; Spadaro, Angelo

2013-10-16

173

Smallpox vaccine.  

PubMed

After an extensive worldwide eradication program, the last nonlaboratory case of smallpox occurred in 1977 in Somalia. In 1972, routine smallpox immunization was discontinued in the United States, and since 1983, vaccine production has been halted. Stockpiled vaccine has been used only for laboratory researchers working on orthopoxviruses. In recent years, there has been concern that smallpox virus stocks may be in the hands of bioterrorists, and this concern has been heightened by the terrorist attack on the World Trade Center and the Pentagon on September 11, 2001. Because most of the population is considered to be nonimmune, there is debate as to whether smallpox immunization should be resumed. This statement reviews the current status of smallpox vaccine, the adverse effects that were associated with smallpox vaccine in the past, and the major proposals for vaccine use. The statement provides the rationale for a policy based on the so-called ring vaccination strategy recommended by the Centers for Disease Control and Prevention, in which cases of smallpox are rapidly identified, infected individuals are isolated, and contacts of the infected individuals as well as their contacts are immunized immediately. PMID:12359807

2002-10-01

174

Biological production of ethanol from coal. Final report  

SciTech Connect

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.

Not Available

1992-12-01

175

Enhanced saccharification of biologically pretreated wheat straw for ethanol production.  

PubMed

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

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

2013-02-01

176

Biological surfactant production in a biological slurry reactor treating diesel fuel contaminated soil.  

PubMed

A sandy loam with aged diesel fuel contamination was treated for 90 days in an 8-L soil slurry-sequencing batch reactor (SS-SBR). The purpose was to investigate biological surfactant production and its effect on slurry properties and reactor performance. The SS-SBR was operated with a 10-day retention time and a 5-day cycle. Track studies were performed to monitor the fluctuation in slurry properties during a single cycle. Surfactants were produced faster than they were degraded or sorbed during the first 1.5 days of each cycle, resulting in increasing concentrations from less than the critical micelle concentration (CMC) to 60 times the CMC and an increase in aqueous diesel fuel concentration from 0 to 1.2 g/L. Only after the concentration of surfactants and emulsified diesel fuel began to decrease through biodegradation (after 1.5 days) was foaming observed. Foam thickness increased from 0 mm at 1.5 days to 48 mm on day 3, and then decreased to 0 mm again by the end of the cycle. Surfactants were completely degraded by the end of each cycle. Coinciding profiles of foam thickness and emulsification capacity (i.e., ability to emulsify spiked hydrocarbon) indicate that foaming resulted from the temporary accumulation of free surfactant molecules. Biological surfactant production occurred without cell multiplication during the first day, but was later growth associated. The ratio of oxygen to diesel fuel consumed was 1.7, and the microorganism yield on a chemical oxygen demand basis (YCOD) was 0.43. PMID:11558308

Cassidy, D P

2001-01-01

177

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

Code of Federal Regulations, 2011 CFR

...Persons who manufacture only in vitro diagnostic products that are not subject to licensing under section 351 of the Public Health Service Act do not report biological product deviations for those products under this section but must report in...

2011-04-01

178

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

Federal Register 2010, 2011, 2012, 2013

...applicant's supply of the product. Manufacturing shutdowns for maintenance or other...biological product. A merger of firms or transfer of an application for...product. An interruption in manufacturing (e.g., contamination of...

2013-11-04

179

Ethics of vaccination programs.  

PubMed

Ethical issues are present at each stage in the vaccine product life cycle, the period extending from the earliest stages of research through the eventual design and implementation of global vaccination programs. Recent developments highlight fundamental principles of vaccine ethics and raise unique issues for ongoing vaccination activities worldwide. These include the 2009-10 H1N1 pandemic influenza vaccination campaign, renewed attention to the potential global eradication of polio, and the ongoing evaluation of vaccine risk controversies, most notably the alleged link between childhood vaccines and autism. These cases present ethical challenges for public health policy-makers, scientists, physicians, and other stakeholders in their efforts to improve the health of individuals, communities, and nations through vaccination. PMID:22440783

Schwartz, Jason L; Caplan, Arthur L

2011-10-01

180

[Design and construction of artificial biological systems for complex natural products biosynthesis].  

PubMed

Natural products (NPs) are important drug pools for human disease prevention and treatment. The great advances in synthetic biology have greatly revolutionized the strategies of NPs development and production. This review entitled with design and construction of artificial biological systems for complex NPs biosynthesis, mainly introduced the progresses in artificial design of synthetic biological parts, naturally mining novel synthetic parts of NPs, the assembly & adaption of the artificial biological modules & systems. PMID:24364351

Wang, Jianfeng; Meng, Hailin; Xiong, Zhiqiang; Wang, Yong

2013-08-01

181

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

PubMed

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 proliferation in cells maintaining receptivity. Mathematical models describing quantitative relationships between consumption of small amounts of oestrogens in meat in addition to greater concentrations from endogenous production, chemical stoichiometry at cellular level and human pathology have not been developed. Such an approach will be necessary to establish 'molecular materiality' of the additional hormone intake as a component of relative risk assessment. The other hormones, although generally less well researched, are similarly subject to a range of tests to determine potentially adverse effects. The resulting limited international consensus relates to the application of the 'precautionary principle' and non-acceptance by the European Commission of the recommendations of the Codex Alimentarius Commission, which determined that meat from cattle, hormone-treated according to good practice, was safe for human consumers. The present review considers the hormone issue in the context of current international social methodology and regulation, recent advances in knowledge of biological activity of hormones and current status of science-based evaluation of food safety and risk for human consumers. PMID:19087409

Galbraith, Hugh

2002-12-01

182

Competency development in antibody production in cancer cell biology  

SciTech Connect

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.

Park, M.S.

1998-12-01

183

Effect of Vaccination Against Coccidiosis in Combination with an Antibacterial Oregano (Origanum vulgare) Compound in Organic Broiler Production  

Microsoft Academic Search

Effects on production and health in broilers vaccinated against coccidiosis (Paracox®, Schering-Plough Animal Health) in combination with an antibacterial organic compound (Orego-Stim®, Meriden Animal Health Ltd.) were investigated. To obtain an environment and infection level similar to practical conditions, experimental floor pens were set up in a commercial broiler chicken house. Orego-Stim® supplement increased live weight and feed intake up

L Waldenstedt

2003-01-01

184

Construction and biological characterization of artificial recombinants between a wild type flavivirus (Kunjin) and a live chimeric flavivirus vaccine (ChimeriVax-JE).  

PubMed

Although the theoretical concern of genetic recombination has been raised related to the use of live attenuated flavivirus vaccines [Seligman, Gould, Lancet 2004;363:2073-5], it has little foundation [e.g., Monath TP, Kanesa-Thasan N, Guirakhoo F, Pugachev K, Almond J, Lang J, et al. Vaccine 2005;23:2956-8]. To investigate biological effects of recombination between a chimeric yellow fever (YF) 17D/Japanese encephalitis (JE) vaccine virus (ChimeriVax-JE) and a wild-type flavivirus Kunjin (KUN-cDNA), the prM-E envelope protein genes were swapped between the two viruses, resulting in new YF 17D/KUN(prM-E) and KUN/JE(prM-E) chimeras. The prM-E genes are easily exchangeable between flavivirues, and thus the exchange was expected to yield the most replication-competent chimeras, while other rationally designed recombinants would be more likely to be crippled or non-viable. The new chimeras proved highly attenuated in comparison with the KUN-cDNA parent, as judged by plaque size and growth kinetics in cell culture, low viremia in hamsters, and reduced neurovirulence/neuroinvasiveness in mice. These data provide strong experimental evidence that the potential of recombinants, should they ever emerge, to cause disease or spread (compete in nature with wild-type flaviviruses) would be indeed extremely low. PMID:17693000

Pugachev, Konstantin V; Schwaiger, Julia; Brown, Nathan; Zhang, Zhen-xi; Catalan, John; Mitchell, Frederick S; Ocran, Simeon W; Rumyantsev, Alexander A; Khromykh, Alexander A; Monath, Thomas P; Guirakhoo, Farshad

2007-09-17

185

Clinical trials with allergen products: in search of biological markers of efficacy.  

PubMed

I discuss herein our efforts to identify biological markers of efficacy in support of the development of sublingual allergy vaccines. Biomarkers are of major interest to facilitate clinical development, for example by predicting safety and efficacy of candidate vaccines or their components (e.g. adjuvants and formulations) on the basis of immunogenicity evaluated in humans. They will be mandatory in the future to evaluate customized recombinant allergy vaccines designed upon component-resolved diagnosis. In this regard, they must ideally be both qualitative and quantitative. Such markers would also be useful to confirm foreseen mechanisms of action potentially associated with successful immunotherapy (e.g. the Treg hypothesis). The recent availability of sophisticated technologies (referred here as the technology push) to assess in details both humoral and cellular arms of the immune system provides new opportunities to identify such markers. In this regard, documenting natural immune responses, most particularly allergen-specific T cell responses in healthy persons, is critical to identify immunological correlates of protection, and thus to design optimal allergy vaccines. PMID:17393738

Moingeon, Philippe

2006-01-01

186

Sustainable production of biologically active molecules of marine based origin.  

PubMed

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

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

187

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

PubMed

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

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

2012-01-01

188

37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.  

Code of Federal Regulations, 2010 CFR

...patent term extension for a human drug, antibiotic drug or human biological product...patent term extension for a human drug, antibiotic drug or human biological product...750 that a patent for a human drug, antibiotic drug or human biological...

2009-07-01

189

37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.  

Code of Federal Regulations, 2010 CFR

...patent term extension for a human drug, antibiotic drug or human biological product...patent term extension for a human drug, antibiotic drug or human biological product...750 that a patent for a human drug, antibiotic drug or human biological...

2010-07-01

190

Understanding Vaccines: What They Are How They Work  

NSDL National Science Digital Library

This is a PDF booklet providing information on vaccines including how they prevent disease, how they are developed and researched, and what the future holds for vaccines in production. Benefits of vaccines, and specific vaccine types are discussed.

2003-07-01

191

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

PubMed

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 sample by sentinel bacteria suggests that antibiotic residues in DG were inactivated during the production process or are present in sublethal concentrations. PMID:23463564

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

2013-05-01

192

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

PubMed Central

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 the original protein. This rapid and easily scalable system may enable the implementation of pCTB to mass vaccination against outbreaks, thereby providing better protection of high-risk populations in developing countries.

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

2013-01-01

193

Use of Recombinant DNA Techniques for the Production of a More Effective Anthrax Vaccine.  

National Technical Information Service (NTIS)

The overall goal of the present research is to construct a safe and effective human anthrax vaccine using recombinant DNA techniques. During the course of this contract, we have isolated and characterized each of the Bacillus anthracis toxin genes. Althou...

D. L. Robertson

1988-01-01

194

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

Federal Register 2010, 2011, 2012, 2013

...pandemic influenza? 3. Improving availability for developing countries. How can we support and stimulate demand for seasonal flu vaccine in middle and lower income countries? Are there other [[Page 55777

2010-09-14

195

Viable adenovirus vaccine prototypes: high-level production of a papillomavirus capsid antigen from the major late transcriptional unit.  

PubMed

Safe, effective, orally delivered, live adenovirus vaccines have been in use for three decades. Recombinant derivatives of the live adenovirus vaccines may prove an economical alternative to current vaccines for a variety of diseases. To explore that possibility, we constructed a series of recombinants that express the major capsid protein (L1) of canine oral papillomavirus (COPV), a model for mucosal human papillomavirus (HPV) infection. Vaccination with virus-like particles (VLPs) composed of recombinant HPV L1 completely prevents persistent HPV infection [Koutsky, L. A., Ault, K. A., Wheeler, C. M., Brown, D. R., Barr, E., Alvarez, F. B., Chiacchierini, L. M. & Jansen, K. U. (2002) N. Engl. J. Med. 347, 1645-1651], suggesting that L1 expressed from recombinant adenoviruses might provide protective immunity. In our recombinants, COPV L1 is incorporated into adenovirus late region 5 (Ad L5) and is expressed as a member of the adenoviral major late transcriptional unit (MLTU). COPV L1 production by the most prolific recombinant is comparable to that of the most abundant adenoviral protein, hexon. COPV L1 production by recombinants is influenced by Ad L5 gene order, the specific mRNA processing signals associated with COPV L1, and the state of a putative splicing inhibitor in the COPV L1 gene. Recombinant COPV L1 protein assembles into VLPs that react with an antibody specific for conformational epitopes on native COPV L1 protein that correlate with protection in vivo. The designs of these recombinants can be applied directly to the production of recombinants appropriate for assessing immunogenicity and protective efficacy in animal models and in human trials. PMID:15767581

Berg, Michael; Difatta, Julie; Hoiczyk, Egbert; Schlegel, Richard; Ketner, Gary

2005-03-22

196

Viable adenovirus vaccine prototypes: High-level production of a papillomavirus capsid antigen from the major late transcriptional unit  

PubMed Central

Safe, effective, orally delivered, live adenovirus vaccines have been in use for three decades. Recombinant derivatives of the live adenovirus vaccines may prove an economical alternative to current vaccines for a variety of diseases. To explore that possibility, we constructed a series of recombinants that express the major capsid protein (L1) of canine oral papillomavirus (COPV), a model for mucosal human papillomavirus (HPV) infection. Vaccination with virus-like particles (VLPs) composed of recombinant HPV L1 completely prevents persistent HPV infection [Koutsky, L. A., Ault, K. A., Wheeler, C. M., Brown, D. R., Barr, E., Alvarez, F. B., Chiacchierini, L. M. & Jansen, K. U. (2002) N. Engl. J. Med. 347, 1645–1651], suggesting that L1 expressed from recombinant adenoviruses might provide protective immunity. In our recombinants, COPV L1 is incorporated into adenovirus late region 5 (Ad L5) and is expressed as a member of the adenoviral major late transcriptional unit (MLTU). COPV L1 production by the most prolific recombinant is comparable to that of the most abundant adenoviral protein, hexon. COPV L1 production by recombinants is influenced by Ad L5 gene order, the specific mRNA processing signals associated with COPV L1, and the state of a putative splicing inhibitor in the COPV L1 gene. Recombinant COPV L1 protein assembles into VLPs that react with an antibody specific for conformational epitopes on native COPV L1 protein that correlate with protection in vivo. The designs of these recombinants can be applied directly to the production of recombinants appropriate for assessing immunogenicity and protective efficacy in animal models and in human trials.

Berg, Michael; DiFatta, Julie; Hoiczyk, Egbert; Schlegel, Richard; Ketner, Gary

2005-01-01

197

IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform.  

PubMed

The quality of a Th1 response can be a prospective correlate of vaccine-mediated protection against certain intracellular pathogens. Using two distinct vaccine platforms, we evaluate the influence of interleukin (IL) 10 production on the magnitude, quality, and protective capacity of CD4(+) T cell responses in the mouse model of Leishmania major infection. Multiparameter flow cytometry was used to delineate the CD4(+) T cell production of interferon (IFN) gamma, IL-2, tumor necrosis factor (TNF), and IL-10 (or combinations thereof) after vaccination. Immunization with a high dose of adenovirus (ADV) expressing leishmanial proteins (MML-ADV) elicited a limited proportion of multifunctional IFN-gamma(+)IL-2(+)TNF(+) Th1 cells, a high frequency of IL-10-producing CD4(+) T cells, and did not protect against subsequent challenge. Surprisingly, in the absence of IL-10, there was no change in the magnitude, quality, or protective capacity of the Th1 response elicited by high-dose MML-ADV. In contrast, after immunization with MML protein and CpG (MML + CpG), IL-10 limited the production of IL-12 by DCs in vivo, thereby decreasing the generation of multifunctional Th1 cells. Consequently, three immunizations with MML + CpG were required for full protection. However, inhibiting IL-10 at the time of immunization enhanced the magnitude and quality of the Th1 response sufficiently to mediate protection after only a single immunization. Overall, we delineate distinct mechanisms by which vaccines elicit protective Th1 responses and underscore the importance of multifunctional CD4(+) T cells. PMID:20530206

Darrah, Patricia A; Hegde, Sonia T; Patel, Dipti T; Lindsay, Ross W B; Chen, Linda; Roederer, Mario; Seder, Robert A

2010-07-01

198

DNA vaccines  

PubMed Central

Since the introduction of DNA vaccines two decades ago, this attractive strategy has been hampered by its low immunogenicity in humans. Studies conducted to improve the immunogenicity of DNA vaccines have shown that understanding the mechanism of action of DNA vaccines might be the key to successfully improving their immunogenicity. Our current understanding is that DNA vaccines induce innate and adaptive immune responses in two ways: (1) encoded protein (or polypeptide) antigen(s) by the DNA plasmid can be expressed in stromal cells (i.e., muscle cells) as well as DCs, where these antigens are processed and presented to naïve CD4 or CD8 T cells either by direct or cross presentation, respectively; and (2) the transfected DNA plasmid itself may bind to an un-identified cytosolic DNA sensor and activate the TBK1-STING pathway and the production of type I interferons (IFNs) which function as an adjuvant. Recent studies investigating double-stranded cytosolic DNA sensor(s) have highlighted new mechanisms in which cytosolic DNA may release secondary metabolites, which are in turn recognized by a novel DNA sensing machinery. Here, we discuss these new metabolites and the possibilities of translating this knowledge into improved immunogenicity for DNA vaccines.

Coban, Cevayir; Kobiyama, Kouji; Jounai, Nao; Tozuka, Miyuki; Ishii, Ken J

2013-01-01

199

Production of a Particulate Hepatitis C Vaccine Candidate by an Engineered Lactococcus lactis Strain?  

PubMed Central

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-?) 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-? and IL-17A as well as the proinflammatory cytokines tumor necrosis factor alpha (TNF-?) 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.

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

2011-01-01

200

Topical Acne Products Can Cause Dangerous Side Effects  

MedlinePLUS

... Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products For Consumers Print this page ... Home For Consumers Consumer Updates Consumer Updates Animal & Veterinary Children's Health Cosmetics Dietary Supplements Drugs Food Medical ...

201

Preventing Tetanus, Diphtheria, and Pertussis Among Adolescents: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, Vol. 55, No. RR-3, March 24, 2006.  

National Technical Information Service (NTIS)

During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologi...

2006-01-01

202

Using noble gases to constrain gas exchange and biological productivity  

NASA Astrophysics Data System (ADS)

The five noble gases (He, Ne, Ar, Kr, and Xe) are biologically and chemically inert, making them useful oceanographic tracers. Moreover, the noble gases have a wide range of solubilities and diffusivities, and thus respond differently to physical forcing. We present here a one year time-series of the five noble gases and the isotope 3He, measured in the upper 400 m of the Sargasso Sea with monthly resolution at the Bermuda Atlantic Time-series Site (BATS). Two profiles of the noble gases in the entire water column down to 4200 m are presented as well. We combine the upper ocean noble gas time-series data, nutrient, oxygen, and hydrographic data from BATS, and a one-dimensional vertical mixed layer model (a modified Price-Weller-Pinkel model) in order to quantify air-sea gas exchange processes. We use inverse modeling to quantify the magnitude of both diffusive gas exchange and air injection processes. The estimates obtained constrain the seasonal time-scale gas exchange rate to a precision of 6% and the bubble injection fluxes to 15%, valid for wind speeds up to 15 m/sec. The overall results suggest that the Wanninkhof quadratic formulation needs to be adjusted downward by approximately 20%. Additionally, 3He is used as a tracer of upwelling nutrients in order to constrain new production. Nutrients in the upper thermocline are well correlated with 3He, and thus 3He and nitrate measurements, combined with estimates of gas exchange, are used to quantify the input of new nutrients into the mixed layer. 3He measurement are also used in conjunction with tritium and oxygen data in order to calculate apparent oxygen utilization rates (AOUR) and thus to estimate export production.

Stanley, R.; Jenkins, W. J.; Lott, D. E.; Doney, S. C.

2007-12-01

203

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

PubMed

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

Stirling, Catrina; Novokova, Viera

2013-09-01

204

[Immuno-contraceptive vaccines].  

PubMed

Results of studies on birth control vaccines accomplished by many research groups within the WHO Special Programe of Research, Development and Research Training in Human Reproduction has been reviewed. The mostly investigated contraceptive vaccines contain human chorionic gonadotropin, and therefore structure, biological role and immunogenicity of the hormone were presented. Also, vaccines obtained on the basis of subunit beta of the human chorionic gonadotropin, its heterodimer with subunit beta of ovine lutropin or C-terminal peptide of beta subunit were described. Results of two phases of clinical trials with immuno-contraceptive vaccines were presented. The use of contraceptive vaccines for treatment of some trophoblastic tumors and the idea of using contraceptive recombinant vaccines were also mentioned. PMID:8657642

Kochanowska, I E; Szewczuk, A

1995-01-01

205

Overview of marker vaccine and differential diagnostic test technology.  

PubMed

Recent advances in molecular biology, immunology, microbiology, genetics and microbial pathogenesis have lead to the development of a wide variety of new approaches for developing safer and more effective vaccines based on designs such as subunit vaccines, gene deleted vaccines, live vectored vaccines, and DNA mediated vaccines. Technology tools can be as basic as identifying naturally occurring strains with deletions that support differentiating infected from vaccinated animal (DIVA) needs or be based on higher technology developments such as improved protein expression and purification methods, transgenic plant- and plant virus-based antigen production, and novel adjuvants that target specific immune responses. These new approaches, when applied to the development of marker vaccines and companion diagnostic test kits hold tremendous potential for developing improved tools for eradication and control programs. Marker vaccines and companion diagnostic test kits must meet the established licensing requirements for purity, potency, safety and efficacy. Efficacy claims are based on evaluation of the level of protection demonstrated in host animal trials and may range from "prevents infection with (a specific agent)", to "for use as an aid in the reduction of disease due to (a specific agent)." The differences in claims and recommendations are a function of the variation in protection elicited by various vaccines. For designing effective eradication programs, vaccine efficacy characteristics such as for reducing susceptibility to infections and spread of infections must be well defined; similarly, diagnostic test performance characteristics (efficacy) must be determined. In addition to data to support efficacy claims, it is imperative that safety of production and use of vaccines be evaluated. During the design of marker vaccines and diagnostic tests, it is important to consider the application of appropriate technologies to improve the safety of these products. Use of recombinant technologies for production of vaccines and/or diagnostic test antigens can reduce the biosafety concerns during production and during use, including human exposure to zoonotic pathogens during production and use, and potential spread of foreign animal disease agents due to loss of biocontainment. In addition, vaccines may induce adverse reactions. It is important to determine the frequency of adverse events and to reduce the likelihood of induction of adverse reactions through proper design. PMID:16257545

Henderson, Louise M

2005-12-01

206

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

PubMed

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 of commercial parent broiler chicken breeders with the FMG vaccine before laying may prevent infection by field M. gallisepticum, and facilitate productive and reproductive performance. PMID:23687149

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

2013-06-01

207

Influence of an immunopotentiator Polyoxidonium on cytokine profile and antibody production in children vaccinated with Priorix.  

PubMed

60 children aged 1-2 years old (32 boys and 28 girls) were vaccinated with Priorix. Vaccinated children included healthy control (19 children, group 1), and children with immunological disturbances such as episodes of respiratory infection. From the latter group, 20 children did not receive (group 2), and 21 children received 0.15 mg/kg of Polyoxidonium simultaneously with the vaccine (group 3).On days 7 and 30 after vaccination, CD-markers on lymphocytes and concentration of specific antibodies, as well as levels of 11 cytokines in serum were evaluated by flow cytometry, ELISA, and multiplex techniques respectively. It was found that injection of Polyoxidonium skewed T helper differentiation to Th2 type. Antibody responses were significantly higher in children with preferable Th2 responses. Children from group 3 possessed higher titers of specific IgG-antibodies. Our study shows that Polyoxidonium could smooth out the immune reaction on vaccination. It is important for children with some immunological disturbances. PMID:22385273

Toptygina, Anna; Semikina, Elena; Alioshkin, Vladimir

2012-10-01

208

Vaccines in a hurry.  

PubMed

Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies. PMID:19460599

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

2009-05-26

209

Developing vaccines against pandemic influenza.  

PubMed Central

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.

Wood, J M

2001-01-01

210

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

Federal Register 2010, 2011, 2012, 2013

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Labeling for Human Prescription Drug and Biological Products--Implementing the PLR Content and Format Requirements.'' This guidance is intended to assist applicants in complying with the content and format requirements of labeling for human prescription drug and biological products. The......

2013-02-25

211

Simultaneous determination of trace levels of ethylmercury and methylmercury in biological samples and vaccines using sodium tetra(n-propyl)borate as derivatizing agent.  

PubMed

Because of increasing awareness of the potential neurotoxicity of even low levels of organomercury compounds, analytical techniques are required for determination of low concentrations of ethylmercury (EtHg) and methylmercury (MeHg) in biological samples. An accurate and sensitive method has been developed for simultaneous determination of methylmercury and ethylmercury in vaccines and biological samples. MeHg and EtHg were isolated by acid leaching (H2SO4-KBr-CuSO4), extraction of MeHg and EtHg bromides into an organic solvent (CH2Cl2), then back-extraction into Milli-Q water. MeHg and EtHg bromides were derivatized with sodium tetrapropylborate (NaBPr4), collected at room temperature on Tenax, separated by isothermal gas chromatography (GC), pyrolysed, and detected by cold-vapour atomic fluorescence spectrometry (CV AFS). The repeatability of results from the method was approximately 5-10% for EtHg and 5-15% for MeHg. Detection limits achieved were 0.01 ng g-1 for EtHg and MeHg in blood, saliva, and vaccines and 5 ng g-1 for EtHg and MeHg in hair. The method presented has been shown to be suitable for determination of background levels of these contaminants in biological samples and can be used in studies related to the health effects of mercury and its species in man. This work illustrates the possibility of using hair and blood as potential biomarkers of exposure to thiomersal. PMID:17340078

Gibicar, Darija; Logar, Martina; Horvat, Nusa; Marn-Pernat, Andreja; Ponikvar, Rafael; Horvat, Milena

2007-05-01

212

Enhanced Assessment of the Health Status of Vaccine Protected Personnel At-Risk to Multiple Biowarfare Agents Using a Novel, Web-Based Clinical Data Management System (CDMS).  

National Technical Information Service (NTIS)

The Special Immunization Program (SIP) Clinic at the U. S. Army Medical Research Institute of Infectious Diseases (USAMRIID) provides investigational vaccines developed as potential biological defense products for Armed Forces personnel. These investigati...

M. J. McCreery J. E. Brown S. C. Mayer E. Boudreau M. Kortepeter

2004-01-01

213

Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation.  

PubMed

Through an immune-mediated graft-versus-leukemia effect, allogeneic hematopoietic stem cell transplantation (HSCT) affords durable clinical benefits for many patients with hematologic malignancies. Nonetheless, subjects with high-risk acute myeloid leukemia or advanced myelodysplasia often relapse, underscoring the need to intensify tumor immunity within this cohort. In preclinical models, allogeneic HSCT followed by vaccination with irradiated tumor cells engineered to secrete GM-CSF generates a potent antitumor effect without exacerbating the toxicities of graft-versus-host disease (GVHD). To test whether this strategy might be similarly active in humans, we conducted a Phase I clinical trial in which high-risk acute myeloid leukemia or myelodysplasia patients were immunized with irradiated, autologous, GM-CSF-secreting tumor cells early after allogeneic, nonmyeloablative HSCT. Despite the administration of a calcineurin inhibitor as prophylaxis against GVHD, vaccination elicited local and systemic reactions that were qualitatively similar to those previously observed in nontransplanted, immunized solid-tumor patients. While the frequencies of acute and chronic GVHD were not increased, 9 of 10 subjects who completed vaccination achieved durable complete remissions, with a median follow-up of 26 months (range 12-43 months). Six long-term responders showed marked decreases in the levels of soluble NKG2D ligands, and 3 demonstrated normalization of cytotoxic lymphocyte NKG2D expression as a function of treatment. Together, these results establish the safety and immunogenicity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic HSCT, and raise the possibility that this combinatorial immunotherapy might potentiate graft-versus-leukemia in patients. PMID:19717467

Ho, Vincent T; Vanneman, Matthew; Kim, Haesook; Sasada, Tetsuro; Kang, Yoon Joong; Pasek, Mildred; Cutler, Corey; Koreth, John; Alyea, Edwin; Sarantopoulos, Stefanie; Antin, Joseph H; Ritz, Jerome; Canning, Christine; Kutok, Jeffery; Mihm, Martin C; Dranoff, Glenn; Soiffer, Robert

2009-09-15

214

Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation  

PubMed Central

Through an immune-mediated graft-versus-leukemia effect, allogeneic hematopoietic stem cell transplantation (HSCT) affords durable clinical benefits for many patients with hematologic malignancies. Nonetheless, subjects with high-risk acute myeloid leukemia or advanced myelodysplasia often relapse, underscoring the need to intensify tumor immunity within this cohort. In preclinical models, allogeneic HSCT followed by vaccination with irradiated tumor cells engineered to secrete GM-CSF generates a potent antitumor effect without exacerbating the toxicities of graft-versus-host disease (GVHD). To test whether this strategy might be similarly active in humans, we conducted a Phase I clinical trial in which high-risk acute myeloid leukemia or myelodysplasia patients were immunized with irradiated, autologous, GM-CSF-secreting tumor cells early after allogeneic, nonmyeloablative HSCT. Despite the administration of a calcineurin inhibitor as prophylaxis against GVHD, vaccination elicited local and systemic reactions that were qualitatively similar to those previously observed in nontransplanted, immunized solid-tumor patients. While the frequencies of acute and chronic GVHD were not increased, 9 of 10 subjects who completed vaccination achieved durable complete remissions, with a median follow-up of 26 months (range 12–43 months). Six long-term responders showed marked decreases in the levels of soluble NKG2D ligands, and 3 demonstrated normalization of cytotoxic lymphocyte NKG2D expression as a function of treatment. Together, these results establish the safety and immunogenicity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic HSCT, and raise the possibility that this combinatorial immunotherapy might potentiate graft-versus-leukemia in patients.

Ho, Vincent T.; Vanneman, Matthew; Kim, Haesook; Sasada, Tetsuro; Kang, Yoon Joong; Pasek, Mildred; Cutler, Corey; Koreth, John; Alyea, Edwin; Sarantopoulos, Stefanie; Antin, Joseph H.; Ritz, Jerome; Canning, Christine; Kutok, Jeffery; Mihm, Martin C.; Dranoff, Glenn; Soiffer, Robert

2009-01-01

215

Emerging Vaccine Informatics  

PubMed Central

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.

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

2010-01-01

216

[Poliovirus vaccine].  

PubMed

To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world. PMID:23189825

Shimizu, Hiroyuki

2012-06-01

217

Biogas Production and Biogas Uses: Biological Principles and Process Technology.  

National Technical Information Service (NTIS)

The report abstracted focuses on the biological and chemical principles allowing both to optimize the fermentative process and to purify the gases produced and provide for an optimal combustion efficiency. Cold fermentation is one of the processes the stu...

A. Wellinger K. Egger K. Sutter

1985-01-01

218

The association between psychosocial factors and vaccine-induced cytokine production  

Microsoft Academic Search

Existing data suggest that immune function is compromised by negative psychosocial factors. We hypothesized that high psychological well being and quality relationships would be associated with vigorous cytokine responses to vaccination. Lymphocytes from 18 individuals were studied for their ability to produce interferon-? (IFN-?) and interleukin-10 (IL-10) with influenza or hepatitis A immunization. Psychological well being and relationship quality were

Mary S. Hayney; Gayle Dienberg Love; Jessica M. Buck; Carol D. Ryff; Burton Singer; Daniel Muller

2003-01-01

219

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

Microsoft Academic Search

The most common lymphoproliferative disease in chickens is Marek's disease (MD), which is caused by the oncogenic herpesvirus Marek's disease virus (MDV). The emergence of hypervirulent pathotypes of MDV has led to vaccine failures, which have become common and which have resulted in serious economic losses in some countries, and a revaccination strategy has been introduced in practice. The mechanism

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

2009-01-01

220

Serum-free Influenza Vaccine Production with MDCK Cells in Wave-bioreactor and 5L-stirred Tank Bioreactor  

Microsoft Academic Search

A serum-free process for influenza virus vaccine production (equine and human) in roller bottles and microcarrier systems\\u000a in 5L-stirred tank and 2Lwave bioreactor (Cytodex 1) is described. MDCK cells were adapted from growth in serum containing\\u000a GMEM medium to serum-free Ex-Cell MDCK medium. Virus titers of 2.0–2.9 log HA units\\/ 100 ?L were obtained. Omission of the\\u000a medium exchange before

Yvonne Genzel; Marlies Fischer; Ruth Olmer; Bastian Schäfer; Claudia Best; Susanne König; Boris Hundt; Udo Reichl

221

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

PubMed Central

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.

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

2004-01-01

222

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)

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.

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

2004-09-01

223

Particulate barium fluxes and their relationships to biological productivity  

NASA Astrophysics Data System (ADS)

To understand better the processes that control the transport of particulate barium through the water column and its preservation in marine sediments, we measured particulate barium fluxes along an equatorial transect at 140°W using moored sediment traps. The fluxes of barium correlate strongly with the fluxes of organic carbon; however, this relationship is non-linear—higher carbon fluxes have proportionately less associated barium. As a result we observe spatial and temporal variations of roughly a factor of three in the barium-to-organic carbon ratio. Understanding this variability may help to define the processes that determine the geochemical behavior of Ba in the oceans. Several hypotheses that could influence the flux of Ba and its relationship to organic carbon flux have been proposed: barite formation in barium- and sulfate-enriched microenvironments formed during particle settling; lateral advection of carbon and barium from continental margins; the influence of seawater barium concentration; and Ba scavenging by aluminosilicates. Our study reveals temporal variability in the Ba/C org values that occurs over timescales of less than one month. Also, depth profiles of carbon and Ba fluxes show that the variability originates at depths less than 1200 m and is conveyed throughout the water column. Both the rapid changes and the upper water column origin of the signals point to upper-ocean biological processes as the predominant cause of the variability in the barium-to-organic carbon ratios. We also observe, however, a 25% increase in Ba flux below 1200 m. The deep sources of Ba could result from barite formation linked to continued organic carbon degradation or from lateral sources of particulate barium. Because the spatial and temporal changes in Ba/C org values correlated to changes in particulate opal and organic carbon fluxes, ocean ecology appears to have an important influence on barium fluxes. A better understanding of the processes that contribute to the particulate barium flux is needed before the accumulation of barium in marine sediments can be used as a quantitative proxy for ocean productivity.

Dymond, Jack; Collier, Robert

224

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

Federal Register 2010, 2011, 2012, 2013

...Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app. 2). Dated: September 26, 2013. Jill Hartzler Warner, Acting Associate Commissioner for Special Medical Programs. [FR Doc. 2013-24025 Filed 10-1-13;...

2013-10-02

225

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

Federal Register 2010, 2011, 2012, 2013

...HEALTH AND HUMAN SERVICES Food and Drug Administration...committee of the Food and Drug Administration...Health (NIH), Building 29B/ Conference...passport, green card, etc...HFM-71), Food and Drug Administration...later than 2 business days before...

2010-08-06

226

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

NASA Technical Reports Server (NTRS)

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

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

1973-01-01

227

The effect of vaccination, ploidy and smolt production regime on pathological melanin depositions in muscle tissue of Atlantic salmon, Salmo salar L.  

PubMed

The presence of melanin in muscle fillets of farmed salmon represents a considerable quality problem for the salmon industry with major economic concerns. In this study, we have examined the presence of abnormal pigmentation in vaccinated versus unvaccinated Atlantic salmon, Salmo salar L., and evaluated possible differences between diploid and triploid fish. Furthermore, the impact of the smolt production regime at ambient (4.5 °C) versus elevated temperature (16 °C) was investigated. Pigmented muscle spots were analysed for the expression of genes involved in melanization (tyrosinase gene family) and immune-related response in addition to morphological investigations. The proportion of fish with intramuscular melanin deposits was not significantly different between vaccinated and unvaccinated fish, regardless of ploidy. However, an interaction between vaccination and smolt regime was shown, where smoltification at elevated temperature after vaccination increased the number of affected individuals compared with vaccination followed by simulated natural smoltification. Furthermore, there were overall more fish with melanin spots amongst the triploids compared with their diploid counterparts. Transcription of the tyrosinase gene family confirmed an onsite melanogenesis in all pigment spots. The histological examination and the expression of the immune-related genes revealed a chronic polyphasic myopathy that was not affected by vaccination, ploidy or smolt production regime. PMID:23646928

Larsen, H A S; Austbø, L; Nødtvedt, A; Fraser, T W K; Rimstad, E; Fjelldal, P G; Hansen, T; Koppang, E O

2014-04-01

228

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

PubMed Central

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

Sanchez-Sampedro, Lucas; Gomez, Carmen Elena; Mejias-Perez, Ernesto; Perez-Jimenez, Eva; Oliveros, Juan Carlos

2013-01-01

229

Production and characterization of vaccines based on flaviviruses defective in replication  

SciTech Connect

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.

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

2006-08-01

230

Leptospirosis vaccines  

PubMed Central

Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

Wang, Zhijun; Jin, Li; Wegrzyn, Alicja

2007-01-01

231

Protection against Fasciola gigantica using paramyosin antigen as a candidate for vaccine production.  

PubMed

Yet no vaccine to protect ruminants against liver fluke infection has been commercialized. In an attempt to develop a suitable vaccine against Fasciola gigantica (F. gigantica) infection in rabbits, using 97 kDa Pmy antigen. It was found that, the mean worm burdens and bile egg count after challenge were reduced significantly by 58.40 and 61.40%, respectively. On the other hand, immunization of rabbits with Pmy induced a significant expression of humoral antibodies (IgM, total IgG, IgG1, IgG2 and IgG4) and different cytokines (IL-6, IL-10, L-12 and TNF-alpha). Among Ig isotypes, IgG2 and IgG4 were most dominant Post-infection (PI) while, recording a low IgG1 level. The dominance of IgG2 and IgG4 suggested late T helper1 (Th1) involvement in rabbit's cellular response. While, the low IgG1 level suggested Th2 response to adult F. gigantica worm Pmy. Among all cytokines, IL-10 was the highest in rabbits immunized with Pmy PI suggesting also the enhancement of Th2 response. It was clear that the native F. gigantica Pmy is considered as a relevant candidate for vaccination against fascioliasis. Also, these data suggested the immunoprophylactic effect of the native F. gigantica Pmy which is mediated by a mixed Th1/Th2 response. PMID:24511686

Abou-Elhakam, H; Rabee, I; El Deeb, S; El Amir, A

2013-11-15

232

Intradermal vaccination by DNA tattooing.  

PubMed

DNA vaccination is an attractive vaccination method. First, the production of plasmid DNA as a vaccine is considerably more cheap and simple than the production of recombinant protein. Second, the expression cassette of DNA vaccines can readily be modified, making DNA vaccines highly flexible. Finally, in animal models, DNA vaccination is able to induce potent cellular immune responses. Over the past decade, the focus in the DNA vaccination field has in large part moved from intramuscular immunization towards dermal administration. As a natural "porte d'entrée" for pathogens, the skin is rich in antigen-presenting cells, which are required for generating an efficient antigen-specific immune response. This chapter describes a DNA vaccination protocol that utilizes a simple tattooing device for the dermal delivery of plasmid DNA. This technique, called DNA tattooing, is capable of generating high frequencies of antigen-reactive T cells in mice and macaques. PMID:24715286

van den Berg, Joost H; Oosterhuis, Koen; Schumacher, Ton N M; Haanen, John B A G; Bins, Adriaan D

2014-01-01

233

Footrot vaccines and vaccination.  

PubMed

Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of acquired immunity. PMID:24736003

Dhungyel, Om; Hunter, James; Whittington, Richard

2014-05-30

234

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

PubMed

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

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

2009-06-25

235

Oceanographic frontal structure and biological production at an ice edge  

Microsoft Academic Search

Marginal ice edge zones (MIZ) are unique frontal systems with air-ice-sea interfaces. Phytoplankton blooms, which occur along the edge of the melting ice pack in spring, are strongly related to the air-ice-sea interactive processes. In spring 1982, during a cruise to the Bering Sea ice pack, hydrographic sections, including standard biological oceanographic parameters, were collected across the MIZ showing such

H. J. Niebauer; V. Alexander

1985-01-01

236

GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination  

PubMed Central

The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-? production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-? is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a “T cell–driven” methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens.

Judkowski, Valeria; Bunying, Alcinette; Ge, Feng; Appel, Jon R.; Law, Kingyee; Sharma, Atima; Raja- Gabaglia, Claudia; Norori, Patricia; Santos, Radleigh G.; Giulianotti, Marc A.; Slifka, Mark K.; Douek, Daniel C.; Graham, Barney S.; Pinilla, Clemencia

2011-01-01

237

Production of Biologically Active Substances by Animal Cells and Its Future Prospect.  

National Technical Information Service (NTIS)

Biotechnology has made a remarkable progress in the last two decades with genetic engineering as the core technology. The authors have observed successful production of a number of biologically active substances employing genetically engineered microorgan...

M. Oishi

1985-01-01

238

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

Code of Federal Regulations, 2013 CFR

37 Patents, Trademarks, and Copyrights 1 2013-07-01...2013-07-01 false Calculation of patent term extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights...

2013-07-01

239

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

Code of Federal Regulations, 2011 CFR

37 Patents, Trademarks, and Copyrights 1 2011-07-01...2011-07-01 false Calculation of patent term extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights...

2011-07-01

240

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

Code of Federal Regulations, 2010 CFR

37 Patents, Trademarks, and Copyrights 1 2010-07-01...2010-07-01 false Calculation of patent term extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights...

2010-07-01

241

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

Code of Federal Regulations, 2012 CFR

37 Patents, Trademarks, and Copyrights 1 2012-07-01...2012-07-01 false Calculation of patent term extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights...

2012-07-01

242

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

Code of Federal Regulations, 2010 CFR

...benefit-to-risk ratio of a biological product shall be considered...effectiveness. (4) A biological product may combine two...rational concurrent preventive therapy or treatment for a significant...recommendations with respect to the biological products falling within...

2010-04-01

243

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

Code of Federal Regulations, 2010 CFR

...benefit-to-risk ratio of a biological product shall be considered...effectiveness. (4) A biological product may combine two...rational concurrent preventive therapy or treatment for a significant...recommendations with respect to the biological products falling within...

2009-04-01

244

Design of clinical trials for therapeutic cancer vaccines development.  

PubMed

Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate. PMID:19835869

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

245

Sustainable Production Process of Biological Mineral Feed Additives  

Microsoft Academic Search

Problem statement: This study discussed the problem of accumulation of Zn and Cu in the topsoil as a result of application of mineral feed additives that possess low bioavailability in anima l diet. The review considered the production process of mineral feed additives in which a product supplies microelements in highly bioavailable form. Enrichment of natural biomass of edible microalgae

Katarzyna Chojnacka; Poland Wroclaw; Marjana Simonic

2009-01-01

246

Biology Needs a Modern Assessment System for Professional Productivity  

ERIC Educational Resources Information Center

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…

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

247

Anthrax vaccines.  

PubMed

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

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

2005-01-01

248

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

Microsoft Academic Search

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

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

249

Process development for the production of an E. coli produced clinical grade recombinant malaria vaccine for Plasmodium vivax  

Microsoft Academic Search

The global eradication of malaria will require the development of vaccines to prevent infection cause by Plasmodium vivax in addition to Plasmodium falciparum. In an attempt to contribute to this effort we have previously reported the cloning and expression of a vaccine based on the circumsporozoite protein of P. vivax. The synthetic vaccine encodes for a full-length molecule encompassing the

Brian A. Bell; James F. Wood; Reeta Bansal; Hatem Ragab; John Cargo III; Michael A. Washington; Chloe L. Wood; Lisa A. Ware; Christian F. Ockenhouse; Anjali Yadava

2009-01-01

250

Advances in methods for the production, purification, and characterization of HIV1 Gag–Env pseudovirion vaccines  

Microsoft Academic Search

HIV pseudovirion or virus-like particle vaccines represent a promising approach for eliciting humoral and cellular immune responses. Pseudovirions present the envelope glycoprotein complex in its authentic trimeric form, and thus have the potential to generate neutralizing antibodies against relevant virion-associated epitopes that may be lacking in protein subunit vaccines. The development of pseudovirion particles as a viable vaccine approach for

Jason Hammonds; Xuemin Chen; Xiugen Zhang; Francis Lee; Paul Spearman

2007-01-01

251

Military vaccines in today's environment  

PubMed Central

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

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

2012-01-01

252

Vaccination against tick-borne encephalitis virus tests specific IgG production ability in patients under immunoglobulin substitution therapy.  

PubMed

To assess B-cell function in patients under immunoglobulin (IgG)-replacement therapy, the non-licensed artificial bacteriophage (?X174)-neo-antigen may be used despite limited availability and experience. Active immunization against tick-borne encephalitis (TBE) is performed in few European countries. To test the feasibility of using licensed TBE vaccination as (neo-)antigen to determine residual or restored B-cell function in patients under regular IgG substitution, TBE-IgG levels were analyzed in 18 patients with ? 1-2 years of regular intravenous or subcutaneous IgG substitution and in pharmaceutical IgG-preparations (n=21 batches, 10 products). Six individuals were boosted against TBE. Although TBE-specific IgG was detectable in concentrates (281-57,100 VieU/0.5 ?L), levels were only borderline in patient sera (n=31, 18 individuals; median 132 VieU; positive >155). Thus, TBE vaccination may be used to test B-cell function under IgG replacement therapy because IgG substitution appears insufficient to yield protective TBE-specific antibody levels in children. PMID:20656033

Seidel, Markus G; Grohmann, Eva; Sadeghi, Kambis; Pollak, Arnold; Heitger, Andreas; Förster-Waldl, Elisabeth

2010-09-14

253

Chemistry and biology of bengamides and bengazoles, bioactive natural products from Jaspis sponges.  

PubMed

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

García-Ruiz, Cristina; Sarabia, Francisco

2014-03-01

254

A downstream process for production of a viable and stable Bacillus cereus aquaculture biological agent  

Microsoft Academic Search

Biological products offer advantages over chemotherapeutics in aquaculture. Adoption in commercial application is lacking\\u000a due to limitations in process and product development that address key end user product requirements such as cost, efficacy,\\u000a shelf life and convenience. In previous studies, we have reported on the efficacy, physiological robustness and low-cost spore\\u000a production of a Bacillus cereus isolate (NRRL 100132). This

Rajesh Lalloo; Dheepak Maharajh; Johann Görgens; Neil Gardiner

2010-01-01

255

Dectin-2-Dependent NKT Cell Activation and Serotype-Specific Antibody Production in Mice Immunized with Pneumococcal Polysaccharide Vaccine  

PubMed Central

Although thymus-independent type 2 antigens generally do not undergo Ig class switching from IgM to IgG, pneumococcal polysaccharide vaccine (PPV) induces the production of serotype-specific IgG. How this happens remains unclear, however. In the present study, PPV immunization induced production of IgG as well as IgM specific for a serotype 3-pneumococcal polysaccharide in the sera of wild-type (WT) mice, but this phenomenon was significantly reduced in Dectin-2 knockout (KO) mice. Immunization with PPV caused IL-12p40 production in WT mice, but this response was significantly reduced in Dectin-2KO mice. Likewise, immunization with PPV activated natural killer T (NKT) cells in WT mice but not in Dectin-2KO mice. Furthermore, administration of ?-galactosylceramide, recombinant (r)IL-12 or rIFN-? improved the reduced IgG levels in Dectin-2KO mice, and treatment with neutralizing anti-IFN-? mAb resulted in the reduction of IgG synthesis in PPV-immunized WT mice. Transfer of spleen cells from PPV-immunized WT mice conferred protection against pneumococcal infection on recipient mice, whereas this effect was cancelled when the transferred spleen cells were harvested from PPV-immunized Dectin-2KO mice. These results suggest that the detection of PPV antigens via Dectin-2 triggers IL-12 production, which induces IFN-? synthesis by NKT cells and subsequently the production of serotype-specific IgG.

Miyasaka, Tomomitsu; Akahori, Yukiko; Toyama, Masahiko; Miyamura, Namiko; Ishii, Keiko; Saijo, Shinobu; Iwakura, Yoichiro; Kinjo, Yuki; Miyazaki, Yoshitsugu; Oishi, Kazunori; Kawakami, Kazuyoshi

2013-01-01

256

Rubella vaccination  

Microsoft Academic Search

Rubella vaccination programmes aim to prevent congenital rubella infections. Previously differing programmes have now converged according to the following principle: First vaccination should be given at the age of 15 months (together with measles and mumps vaccine) to both boys and girls, in order to diminish the circulation of the wild virus. Teenage girls require (re-)vaccination to ensure their immunity.

J. Forster

1988-01-01

257

Biological validation of bio-engineered red blood cell productions.  

PubMed

The generation in vitro of cultured red blood cells (cRBC) could become an alternative to classical transfusion products. However, even when derived from healthy donors, the cRBC generated in vitro from hematopoietic stem cells may display alterations resulting from a poor controlled production process. In this context, we attempted to monitor the quality of the transfusion products arising from new biotechnologies. For that purpose, we developed an in vitro erythrophagocytosis (EP) test with the murine fibroblast cell line MS-5 and human macrophages (reference method). We evaluated 38 batches of cRBC, at the stage of reticulocyte, generated from CD34(+) cells isolated from placental blood or by leukapheresis. We showed that (i) the EP test performed with the MS-5 cell line was sensitive and can replace human macrophages for the evaluation of cultured cells. (ii) The EP tests revealed disparities among the batches of cRBC. (iii) The viability of the cells (determined by calcein-AM test), the expression of CD47 (antiphagocytosis receptor) and the externalization of phosphatidylserine (PS, marker of phagocytosis) were not critical parameters for the validation of the cRBC. (iv) Conversely, the cell deformability determined by ektacytometry was inversely correlated with the intensity of the phagocytic index. Assuming that the culture conditions directly influence the quality of the cell products generated, optimization of the production mode could benefit from the erythrophagocytosis test. PMID:23040561

Giarratana, Marie-Catherine; Marie, Tiffany; Darghouth, Dhouha; Douay, Luc

2013-02-01

258

Immunologic Monitoring of Cancer Vaccine Therapy: Results of a Workshop Sponsored by the Society for Biological Therapy  

Microsoft Academic Search

Summary: The Society for Biological Therapy held a Workshop last fall devoted to immune monitoring for cancer immunotherapy trials. Participants included members of the academic and pharmaceutical communities as well as the National Cancer Institute and the Food and Drug Administration. Discussion focused on the relative merits and appropriate use of various immune monitoring tools. Six breakout groups dealt with

Ulrich Keilholz; Jeffrey Weber; James H. Finke; Dmitry I. Gabrilovich; W. Martin Kast; Mary L. Disis; John M. Kirkwood; Carmen Scheibenbogen; Jeff Schlom; Vernon C. Maino; H. Kim Lyerly; Peter P. Lee; Walter Storkus; Franceso Marincola; Alexandra Worobec; Michael B. Atkins

259

Synthetic biology tools for bioprospecting of natural products in eukaryotes.  

PubMed

Filamentous fungi have the capacity to produce a battery of natural products of often unknown function, synthesized by complex metabolic pathways. Unfortunately, most of these pathways appear silent, many in intractable organisms, and their products consequently unidentified. One basic challenge is the difficulty of expressing a biosynthesis pathway for a complex natural product in a heterologous eukaryotic host. Here, we provide a proof-of concept solution to this challenge and describe how the entire penicillin biosynthesis pathway can be expressed in a heterologous host. The method takes advantage of a combination of improved yeast in vivo cloning technology, generation of polycistronic mRNA for the gene cluster under study, and an amenable and easily manipulated fungal host, i.e., Aspergillus nidulans. We achieve expression from a single promoter of the pathway genes to yield a large polycistronic mRNA by using viral 2A peptide sequences to direct successful cotranslational cleavage of pathway enzymes. PMID:24631120

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

2014-04-24

260

Combination biological and microwave treatments of used rubber products  

DOEpatents

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.

Fliermans, Carl B. (Augusta, GA); Wicks, George G. (Aiken, SC)

2002-01-01

261

Pricing of new vaccines  

PubMed Central

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

McGlone, Sarah M

2010-01-01

262

Biological production off Southern California is linked to climatic change  

Microsoft Academic Search

To obtain clues about how coastal primary production might be affected by interannual and interdecadal changes in climate, we studied marine laminated sediments from the center of the Santa Barbara Basin. We report here a large decrease in the flux of diatoms between the periods 1954–1972 and 1973–1986, by a factor of five, and sustained reductions from 1973 to 1978

Carina B. Lange; Susan K. Burke; Wolfgang H. Berger

1990-01-01

263

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

Microsoft Academic Search

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

Albert Farrugia

2006-01-01

264

2-Pyrone natural products and mimetics: isolation, characterisation and biological activity.  

PubMed

The review summarises natural products containing the 2-pyrone moiety. An emphasis has been placed upon the biological activity associated with 2-pyrones, particularly with respect to potential therapeutic or anti-microbial agents. Where appropriate, non-natural 2-pyrone analogues are discussed, particularly those derived from natural product lead compounds. PMID:16010346

McGlacken, Gerard P; Fairlamb, Ian J S

2005-06-01

265

Potentials and Limitations in the Use of Ionizing Radiation in the Production of Vaccines.  

National Technical Information Service (NTIS)

A brief explanation of potential effects of ionizing radiation on macromolecules of biological relevance is followed by an exposition of the most important applications of ionizing radiation. Reference is made also to the advantages and disadvantages of r...

H. Richter

1975-01-01

266

Time-Ordered Product Expansions for Computational Stochastic Systems Biology  

PubMed Central

The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie’s Stochastic Simulation Algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differ-ential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion (TOPE) can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems.

Mjolsness, Eric

2013-01-01

267

Time-ordered product expansions for computational stochastic system biology.  

PubMed

The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie's stochastic simulation algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems. PMID:23735739

Mjolsness, Eric

2013-06-01

268

Biological production of hydrogen from cellulose by natural anaerobic microflora  

Microsoft Academic Search

The capability of natural anaerobic microflora to produce hydrogen was examined with artificial wastewater containing cellulose. The microflora in sludge compost was found to produce a significant amount of hydrogen (2.4 mol\\/mol-hexose). Among the fermentation products other than hydrogen and carbon dioxide, the lower fatty acids, mainly acetate and butyrate, constituted more than approximately 90% of the total soluble metabolites.

Yoshiyuki Ueno; Tatsushi Kawai; Susumu Sato; Seiji Otsuka; Masayoshi Morimoto

1995-01-01

269

Some Biological Effects of Carbamoyloxyurea, an Oxidation Product of Hydroxyurea  

PubMed Central

Carbamoyloxyurea, an oxidation product of hydroxyurea, is bactericidal for Escherichia coli. Drug-induced killing is independent of cellular metabolism; ribonucleic acid and protein syntheses are the processes most affected, and the lethal action is accompanied by degradation of cellular deoxyribonucleic acid. In all of these effects the drug differs from hydroxyurea, a primarily bacteriostatic agent that inhibits deoxyribonucleic acid synthesis, whose lethal action ultimately depends on cellular activity.

Rosenkranz, Herbert S.

1970-01-01

270

Production and biological activity of rebeccamycin, a novel antitumor agent.  

PubMed

An actinomycete, strain C-38,383, was selected in a screening program for the isolation of novel antitumor agents. A yellow crystalline product, named rebeccamycin, was isolated from the mycelium and was found to have activity against P388 leukemia, L1210 leukemia and B16 melanoma implanted in mice. Rebeccamycin inhibits the growth of human lung adenocarcinoma cells (A549) and produces single-strand breaks in the DNA of these cells. No DNA-protein cross-links were detected. A related antibiotic, staurosporine, is produced by Streptomyces staurosporeus and Streptomyces actuosus. Strain C-38,383 was found to resemble closely strains of Nocardia aerocolonigenes recently renamed Saccharothrix aerocolonigenes. A strain selection isolate without aerial mycelium, C-38,383-RK-1, failed to produce rebeccamycin while a strain with aerial mycelium, C-38,383-RK-2, was found to be a suitable strain for production. A description of the producing strain is presented and its taxonomic position is reviewed. A fermentor containing 37 liters of production medium gave a rebeccamycin yield of 663 mg/liter after 204 hours of incubation with strain C-38,383-RK-2. PMID:3112080

Bush, J A; Long, B H; Catino, J J; Bradner, W T; Tomita, K

1987-05-01

271

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

PubMed

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

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

2007-08-01

272

Effect of Preexisting Immunity to Adenovirus on Transgene Product-Specific Genital T Cell Responses on Vaccination of Mice With a Homologous Vector  

PubMed Central

We evaluated changes in global and human immunodeficiency virus (HIV)–specific genital T cells after vaccination of female mice with a replication-defective adenovirus vector of human serotype 5 (AdHu5) expressing Gag protein of HIV-1, in the presence or absence of preexisting immunity to the vaccine carrier. Our data show that preexisting immunity causes a rapid and transient decrease of genital CD4+ T cells without increasing the expression of chemokine (C-C motif) receptor 5. Furthermore, preexposure to AdHu5 affects long-term alterations in the magnitude and quality of vaccine-induced Gag-specific CD8+ T cell responses. AdHu5-specific antibodies interfere with the induction of transgene product–specific CD8+ T cell responses in systemic compartments, whereas some mechanism other than antibodies also seems to affect those that home to the genital tract.

Haut, Larissa Herkenhoff; Ratcliffe, Sarah; Pinto, Aguinaldo Roberto

2011-01-01

273

Hybridoma-Derived Idiotype Vaccine for Lymphoma: Approval Must Wait  

PubMed Central

Hybridoma-derived idiotype vaccines have been used for the experimental treatment of human lymphoma over the last twenty years, providing evidence of biological efficacy, clinical efficacy and clinical benefit. However, the product that has come closer to regulatory approval is unlikely to clear that hurdle due to the insufficiently robust data obtained in a recently closed clinical trial. This review aims at discussing the reasons for hybridoma-derived idiotype vaccines, more difficult to produce but also more successful than recombinant idiotype vaccines so far, are unlikely to gain regulatory approval. In particular, it is necessary to examine the many peculiar features of this therapeutic approach in a broader context, with special attention to concepts like customized active immunotherapy and randomization. Most published trials based on hybridoma-derived idiotype vaccines are being analyzed, together with the yet non-peer reviewed data from the only randomized study conducted so far with this product, and with the main trials on recombinant idiotype vaccines for thorough comparison. All in all, the sole randomized trial ever conducted on hybridoma-derived idiotype vaccines failed to achieve its primary clinical end point because of an insufficient accrual and because the statistical significance achieved was not as stringent as required for regulatory approval.

Bendandi, Maurizio

2010-01-01

274

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

PubMed Central

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

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

2010-01-01

275

Mycobacterium bovis BCG Vaccination Augments Interleukin-8 mRNA Expression and Protein Production in Guinea Pig Alveolar Macrophages Infected with Mycobacterium tuberculosis  

PubMed Central

Alveolar macrophages are likely the first cell type to encounter Mycobacterium tuberculosis in a pulmonary infection, resulting in the production of chemokines. In order to evaluate this response, alveolar macrophages harvested from nonvaccinated and Mycobacterium bovis BCG-vaccinated guinea pigs were infected in vitro with live M. tuberculosis H37Ra or H37Rv (multiplicity of infection, 1:1) or cultured with lipopolysaccharide (10 ?g/ml) for 3, 12, and 24 h. Interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was determined by real-time PCR. Culture supernatants were assayed for guinea pig IL-8 protein by using a human IL-8 enzyme-linked immunosorbent assay kit. Alveolar macrophages harvested from BCG-vaccinated guinea pigs produced significantly more mRNA and protein for IL-8 than alveolar macrophages harvested from nonvaccinated guinea pigs at 12 and 24 h poststimulation or postinfection. Infection with attenuated M. tuberculosis (H37Ra) stimulated alveolar macrophages isolated from BCG-vaccinated guinea pigs to produce significantly more IL-8 mRNA than did alveolar macrophages infected with a virulent strain (H37Rv) at 12 and 24 h postinfection. Significant MCP-1 mRNA production was also detected in stimulated or infected alveolar macrophages; however, prior vaccination did not significantly affect levels of MCP-1 mRNA. Alveolar macrophages isolated from BCG-vaccinated guinea pigs produced significantly more IL-8 mRNA and protein when stimulated for 24 h with heat-killed H37Ra, heat-killed H37Rv, and H37Rv cell wall, but not mannose-capped lipoarabinomannan (ManLAM), than did cells stimulated with media alone. These observations indicate that prior vaccination may alter very early events in the M. tuberculosis-infected lung.

Lyons, Mark J.; Yoshimura, Teizo; McMurray, David N.

2002-01-01

276

[The problems of vaccination against chlamydial abortion in sheep].  

PubMed

Different vaccines used against chlamydial abortion in sheep are described. Problems associated with insufficient immunity after vaccination are discussed. Reasons for failure of certain vaccine preparations are addressed. Finally new developments in vaccine production are introduced which might be useful in solving problems still existing in the prevention of chlamydial abortion in sheep by vaccination. PMID:1796460

Thiele, D

1991-12-01

277

A limulus amoebocyte lysate activating activity (LAL activity) that lacks biological activities of endotoxin found in biological products.  

PubMed

Pyrogenic substances in influenza HA (IHA) vaccine have been controlled by the pyrogen test or the mouse body weight decreasing toxicity (BWD) test. We examined the possibility of replacing the animal tests with the endotoxin test Commercial IHA vaccines were found to show considerable levels of LAL activity ranging from 0.2 to 160 EU/ml. However, a batch of the vaccine having even 100 EU/ml of LAL activity showed neither pyrogenicity in rabbits nor tumor necrosis factor alpha (TNF-alpha) induction in RAW264.7 cells. The LAL activity of IHA vaccine was abolished by a monoclonal antibody that recognizes LPS-binding epitope of LAL factor C. The activity of IHA vaccine showed different physicochemical properties from those of LAL activity of endotoxin. LAL activity of endotoxin is known to be sensitive to polymyxin B treatment and was found to be resistant to polyoxyethylene 10 cetyl ether (Brij56) treatment. On the contrary, the LAL activity of IRA vaccine was shown to be resistant to polymyxin B but sensitive to Brij56 treatment. The difference in sensitivity of the two LAL activities to polymyxin B and Brij56 might suggest the possibility of their discriminative measurements. PMID:12363016

Ochia, Masaki; Tamura, Hiroshi; Yamamoto, Akihiko; Aizawa, Maki; Kataoka, Michiyo; Toyoizumi, Hiromi; Horiuchi, Yoshinobu

2002-01-01

278

Biological production of hydroxylated aromatics: Optimization strategies for Pseudomonas putida S12  

Microsoft Academic Search

To replace environmentally unfriendly petrochemical production processes, the demand for bio-based production of organic chemicals is increasing. This thesis focuses on the biological production of hydroxylated aromatics from renewable substrates by engineered P. putida S12 including several cases of strain improvement.\\u000aChapter 2 describes the construction of a P. putida S12 strain that produces p-hydroxybenzoate\\u000avia the aromatic amino acid

A. Verhoef

2010-01-01

279

Maximum entropy production principle in physics, chemistry and biology  

NASA Astrophysics Data System (ADS)

The tendency of the entropy to a maximum as an isolated system is relaxed to the equilibrium (the second law of thermodynamics) has been known since the mid-19th century. However, independent theoretical and applied studies, which suggested the maximization of the entropy production during nonequilibrium processes (the so-called maximum entropy production principle, MEPP), appeared in the 20th century. Publications on this topic were fragmented and different research teams, which were concerned with this principle, were unaware of studies performed by other scientists. As a result, the recognition and the use of MEPP by a wider circle of researchers were considerably delayed. The objectives of the present review consist in summation and analysis of studies dealing with MEPP. The first part of the review is concerned with the thermodynamic and statistical basis of the principle (including the relationship of MEPP with the second law of thermodynamics and Prigogine's principle). Various existing applications of the principle to analysis of nonequilibrium systems will be discussed in the second part.

Martyushev, L. M.; Seleznev, V. D.

2006-04-01

280

SBBGR technology for minimising excess sludge production in biological processes.  

PubMed

This paper reports the results of an investigation aimed at evaluating the performance of an innovative technology (SBBGR system - Sequencing Batch Biofilter Granular Reactor), characterised by a low sludge production, for treating municipal wastewater at demonstrative scale. The results have shown that even at the maximum investigated organic load (i.e., 2.5 kg COD/m(3) d), the plant removed 80% of COD, total suspended solids and nitrogen content with relative residual concentrations lower than the Italian limits for discharge into soil. The process was characterised by a very low sludge production (i.e., 0.12-0.14 kg TSS/kg COD(removed)) ascribable to the high sludge age in the system (thetac >120 d). Molecular in situ detection methods and microscopy staining procedures were employed in combination with the traditional measurements (oxygen uptake rate and total protein content) to evaluate both the microbial activity and composition, and the structure of the biomass. A stable presence of active bacterial populations (mainly Proteobacteria) was found within compact and dense aggregates. PMID:20137803

Di Iaconi, Claudio; De Sanctis, Marco; Rossetti, Simona; Ramadori, Roberto

2010-03-01

281

BIOLOG  

EPA Science Inventory

BIOLOG contains more than 43,000 citations to literature on microbial degradation and toxicity of more than 6,000 chemicals. Records are organized by CAS Registry Number and by 6 categories (i.e., biodegradation/toxicity; oxygen condition (anaerobic/aerobic); culture type (pure e...

282

Chemokines as Cancer Vaccine Adjuvants  

PubMed Central

We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs) and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

Bobanga, Iuliana D.; Petrosiute, Agne; Huang, Alex Y.

2014-01-01

283

Advances in influenza vaccination  

PubMed Central

Influenza virus infections yearly cause high morbidity and mortality burdens in humans, and the development of a new influenza pandemic continues to threaten mankind as a Damoclean sword. Influenza vaccines have been produced by using egg-based virus growth and passaging techniques that were developed more than 60 years ago, following the identification of influenza A virus as an etiological agent of seasonal influenza. These vaccines aimed mainly at eliciting neutralizing antibodies targeting antigenically variable regions of the hemagglutinin (HA) protein, which requires regular updates to match circulating seasonal influenza A and B virus strains. Given the relatively limited protection induced by current seasonal influenza vaccines, a more universal influenza vaccine that would protect against more—if not all—influenza viruses is among the largest unmet medical needs of the 21st century. New insights into correlates of protection from influenza and into broad B- and T-cell protective anti-influenza immune responses offer promising avenues for innovative vaccine development as well as manufacturing strategies or platforms, leading to the development of a new generation of vaccines. These aim at the rapid and massive production of influenza vaccines that provide broad protective and long-lasting immunity. Recent advances in influenza vaccine research demonstrate the feasibility of a wide range of approaches and call for the initiation of preclinical proof-of-principle studies followed by clinical trials in humans.

Reperant, Leslie A.; Rimmelzwaan, Guus F.

2014-01-01

284

CHEMICAL AND BIOLOGICAL CHARACTERIZATION OF PRODUCTS OF INCOMPLETE COMBUSTION FROM THE SIMULATED FIELD BURNING OF AGRICULTURAL PLASTIC  

EPA Science Inventory

The article describes chemical and biological analyses performed to characterize products of incomplete combustion emitted during the simulated open field burning of agricultural plastic. The study highlights the benefits of a combined chemical/biological approach to characteizin...

285

Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases  

PubMed Central

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

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

2014-01-01

286

Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases.  

PubMed

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

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

2014-01-01

287

21 CFR 610.53 - Dating periods for licensed biological products.  

Code of Federal Regulations, 2010 CFR

... Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed ......do Not...do Not applicable 2 years. 5. Pertussis Immune Globulin (Human) 3 years...Serum 1 year 2 years 5 years. Pertussis Vaccine ......do Not...

2010-04-01

288

21 CFR 610.53 - Dating periods for licensed biological products.  

Code of Federal Regulations, 2011 CFR

... Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed ......do Not...do Not applicable 2 years. 5. Pertussis Immune Globulin (Human) 3 years...Serum 1 year 2 years 5 years. Pertussis Vaccine ......do Not...

2011-04-01

289

21 CFR 610.53 - Dating periods for licensed biological products.  

Code of Federal Regulations, 2010 CFR

... Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed ......do Not...do Not applicable 2 years. 5. Pertussis Immune Globulin (Human) 3 years...Serum 1 year 2 years 5 years. Pertussis Vaccine ......do Not...

2009-04-01

290

Studies on Production and Biological Potential of Prodigiosin by Serratia marcescens.  

PubMed

Efficacy of Serratia marcescens for pigment production and biological activity was investigated. Natural substrates like sweet potato, mahua flower extract (Madhuca latifolia L.), and sesam at different concentrations were taken. As a carbon source microorganism favored potato powder was followed by sesam and mannitol, and as nitrogen source casein hydrolysate was followed by yeast and malt extract. The effect of inorganic salts on pigment production was also studied. At final optimized composition of suitable carbon, nitrogen source, and trace materials and at suitable physiological conditions, prodigiosin production was 4.8 g L(-1). The isolated pigment showed antimicrobial activity against different pathogenic bacteria and fungi. Extracted pigment was characterized by spectroscopy, Fourier transform infrared (FTIR), and thin layer chromatography (TLC) which confirm production of biological compound prodigiosin. This study suggests that use of sweet potato powder and casein can be a potential alternative bioresource for commercial production of pigment prodigiosin. PMID:24781979

Suryawanshi, Rahul K; Patil, Chandrashekhar D; Borase, Hemant P; Salunke, Bipinchandra K; Patil, Satish V

2014-07-01

291

Vaccine therapy for pancreatic cancer  

PubMed Central

Pancreatic cancer is a lethal disease and currently available therapies have significant limitations. Pancreatic cancer is thus an ideal setting for the development of novel treatment modalities such as immunotherapy. However, relevant obstacles must be overcome for immunotherapeutic regimens against pancreatic cancer to be successful. Vaccine therapy relies on the administration of biological preparations that include an antigen that (at least ideally) is specifically expressed by malignant cells, boosting the natural ability of the immune system to react against neoplastic cells. There are a number of ways to deliver anticancer vaccines. Potent vaccines stimulate antigen presentation by dendritic cells, hence driving the expansion of antigen-specific effector and memory T cells. Unlike vaccines given as a prophylaxis against infectious diseases, anticancer vaccines require the concurrent administration of agents that interfere with the natural predisposition of tumors to drive immunosuppression. The safety and efficacy of vaccines against pancreatic cancer are nowadays being tested in early phase clinical trials.

Salman, Bulent; Zhou, Donger; Jaffee, Elizabeth M; Edil, Barish H; Zheng, Lei

2013-01-01

292

Therapeutic vaccines against infectious diseases.  

PubMed

Therapeutic vaccines against chronic infectious diseases aim at eliciting broad humoral and cellular immune responses against multiple target antigens. Importantly, the development of such vaccines will help to establish surrogate markers of protection in humans and thus will augment the subsequent development of efficient prophylactic vaccines. A combination of synthetic small-molecule drugs and immunotherapeutics is likely to represent a powerful means of controlling chronic infections in the future. Challenges faced in developing therapeutic vaccines include the following: first, overcoming the potential impairment of immune responses due to established infection; second, optimizing schedules of vaccine administration in combination with standard of care chemotherapy; and third, defining what biological and immunological read-outs should be used to infer vaccine efficacy. PMID:14572538

Moingeon, Philippe; Almond, Jeffrey; de Wilde, Michel

2003-10-01

293

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

SciTech Connect

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

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

2010-08-01

294

Covalent albumin microparticles as an adjuvant for production of mucosal vaccines against hepatitis B.  

PubMed

Covalently modified albumin (BSA) microparticles were developed for potential use as an adjuvant in mucosal vaccines against hepatitis B. To synthesize consistent protein particles, a covalent approach was proposed to modify BSA. Our strategy was to bond maleic anhydride (MA) molecules to BSA structure by nucleophilic reaction for further radical cross-linking/polymerization reaction with N',N'-dimethylacrylamide (DMAAm). The presence of poly(N',N'-dimethylacrylamide) in the protein network enables the microparticles to show well-defined, homogeneous forms. Cytotoxicity tests showed that the cytotoxic concentration for 50% of VERO cells (CC50) was 216.25 ± 5.30 ?g mL(-1) in 72 h of incubation. The obtained CC50 value is relatively low for an incubation time of 72 h, suggesting an acceptable biocompatibility. Assay of total protein showed that the encapsulation efficiency of the microparticles with hepatitis B surface antigen (HBsAg) was 77.7 ± 0.2%. For the reference sample, which was incubated without HBsAg, the quantity of protein was below the limit of detection. PMID:23863080

Sitta, Danielly L A; Guilherme, Marcos R; Garcia, Francielle P; Cellet, Thelma S P; Nakamura, Celso V; Muniz, Edvani C; Rubira, Adley F

2013-09-01

295

PRIORITIZATION OF DELAYED VACCINATION FOR PANDEMIC INFLUENZA  

PubMed Central

Limited production capacity and delays in vaccine development are major obstacles to vaccination programs that are designed to mitigate a pandemic influenza. In order to evaluate and compare the impact of various vaccination strategies during a pandemic influenza, we developed an age/risk-structured model of influenza transmission, and parameterized it with epidemiological data from the 2009 H1N1 influenza A pandemic. Our model predicts that the impact of vaccination would be considerably diminished by delays in vaccination and staggered vaccine supply. Nonetheless, prioritizing limited H1N1 vaccine to individuals with a high risk of complications, followed by school-age children, and then preschool-age children, would minimize an over-all attack rate as well as hospitalizations and deaths. This vaccination scheme would maximize the benefits of vaccination by protecting the high-risk people directly, and generating indirect protection by vaccinating children who are most likely to transmit the disease.

Shim, Eunha

2013-01-01

296

[Japanese encephalitis vaccine].  

PubMed

Japanese encephalitis is a mosquito-borne flaviviral infection, which has a wide distribution in Asian countries, including Japan. The clinical illness may manifest as a febrile headache syndrome, aseptic meningitis, or encephalitis with a number of cases of subclinical infection. Japanese encephalitis is a vaccine-preventable disease. The mouse brain derived inactivated vaccine was first developed in Japan in 1950s. In 2009, this original form was replaced by the Vero cell derived product. The results of clinical trial and post marketing investigation on the Vero cell derived inactivated vaccine showed good immunogenicity and safety profile. High immunization coverage should be encouraged to prevent people from Japanese encephalitis. PMID:21922756

Nakano, Takashi

2011-09-01

297

Aids Vaccines.  

National Technical Information Service (NTIS)

The invention provides vaccination protocols for administering immunogens to a primate host in order to promote the formation of neutralizing antibodies (NAbs) against primate immunodeficiency viruses. In some embodiments, the vaccination protocols compri...

L. Stamataos N. L. Haigwood W. Blay

2005-01-01

298

Research in advance for FMD Novel Vaccines  

PubMed Central

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

2011-01-01

299

Vaccine candidates in STD.  

PubMed

Sexually transmitted diseases (STDs) are caused by organisms that infect the mucosal surfaces of the genitourinary tract. In spite of its public health importance, current STD vaccine research lags behind work against pathogens that target another mucosal region, the respiratory tract. In the latter case, live-attenuated viral vaccines, killed whole-cell bacterial vaccines, subunit/protein bacterial vaccines, and bacterial polysaccharide vaccines have been enormously successful. To move STD vaccine research forward, complex issues must be resolved. Those include selection of an appropriate antigen (e.g. scientific feasibility and intellectual property rights), the manufacture of the vaccine (e.g. delivery systems, formulation processes, and production steps), and the appropriate public health approach (e.g. medical indications and marketing aspects). Particular scientific problems have delayed STD vaccine development, like incomplete attenuation (human herpes simplex virus type 2), accentuated immunopathology (Chlamydia trachomatis), poor immunogenicity (Treponema pallidum), and broad antigenic heterogeneity (Neisseria gonorrhoeae). Nevertheless, efforts continue with the use of protein antigens: for example, the haemolysin toxoid of Haemophilus ducreyi; the major outer membrane protein(s) of N. gonorrhoeae and C. trachomatis; the glycoprotein D of human herpes simplex virus type 2; and the proteins E6 and E7 of human papilloma virus. It may be predicted that eventual STD vaccines (administered either for prophylaxis or for therapy) will use approaches that include (1) live-attenuated viruses, (2) subunit proteins or inactivated whole organisms given with mucosal adjuvants or with cellular immune response adjuvants, and (3) DNA plasmids expressing the vaccine antigen. PMID:12537725

Fletcher, Mark A

2002-12-01

300

Vaccines against nicotine.  

PubMed

Medications against any dependence-inducing drug face a dilemma: if they are efficient, they will induce withdrawal symptoms and the patient is likely to stop taking his medication. Anti drug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting rather with the drug in the blood than with a receptor in the brain, the vaccines are, in addition, free of side effects due to central interaction. For drugs like nicotine interacting with different types of receptors in many organs, this is a further advantage. There are three reasons that anti drug vaccines have first been developed against nicotine. Firstly, in most parts of the world 20 to 50% of the adult population smoke and any smoking cessation treatment will have an important impact on public health and be commercially a very attractive product. The second reason are the smokers themselves, who would like to quit in significant numbers and who have shown good compliance for any form of treatment. Thirdly, the quantities of cocaine or heroine taken by dependant persons are higher than the quantity of nicotine per cigarette, which makes an anti nicotine vaccine the easier vaccine project. Three anti nicotine vaccines are today in an advanced stage of clinical evaluation. We report here how those vaccines work, on the progress of the trials and future developments to expect. Results show that the efficiency of the vaccines is directly related to the antibody levels of the probates, a fact which will help to optimize further the vaccine effect. We expect the vaccines to appear on the market during a time window between 2009 and 2011. PMID:19276649

Cerny, Erich H; Cerny, Thomas

2009-04-01

301

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

NASA Astrophysics Data System (ADS)

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

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

2009-04-01

302

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

PubMed

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

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

2013-11-01

303

The Role of Synthetic Biology in the Design of Microbial Cell Factories for Biofuel Production  

PubMed Central

Insecurity in the supply of fossil fuels, volatile fuel prices, and major concerns regarding climate change have sparked renewed interest in the production of fuels from renewable resources. Because of this, the use of biodiesel has grown dramatically during the last few years and is expected to increase even further in the future. Biodiesel production through the use of microbial systems has marked a turning point in the field of biofuels since it is emerging as an attractive alternative to conventional technology. Recent progress in synthetic biology has accelerated the ability to analyze, construct, and/or redesign microbial metabolic pathways with unprecedented precision, in order to permit biofuel production that is amenable to industrial applications. The review presented here focuses specifically on the role of synthetic biology in the design of microbial cell factories for efficient production of biodiesel.

Colin, Veronica Leticia; Rodriguez, Analia; Cristobal, Hector Antonio

2011-01-01

304

Biological sludge solubilisation for reduction of excess sludge production in wastewater treatment process.  

PubMed

A novel sludge disintegration system (JFE-SD system) was developed for the reduction of excess sludge production in wastewater treatment plants. Chemical and biological treatments were applied to disintegrate excess sludge. At the first step, to enhance biological disintegration, the sludge was pretreated with alkali. At the second step, the sludge was disintegrated by biological treatment. Many kinds of sludge degrading microorganisms integrated the sludge. The efficiency of the new sludge disintegration system was confirmed in a full-scale experiment. The JFE-SD system reduced excess sludge production by approximately 50% during the experimental period. The quality of effluent was kept at quite a good level. Economic analysis revealed that this system could significantly decrease the excess sludge treatment cost. PMID:17087369

Yamaguchi, T; Yao, Y; Kihara, Y

2006-01-01

305

A systems biology approach to optimising hosts for industrial protein production.  

PubMed

The vast number of expression hosts available for recombinant protein production have a variety of advantages and disadvantages; none, however, is globally optimal and host selection is frequently a compromise. Strain development requires a holistic approach, which systems biology can supply by delineating experimental data sets with computational modelling. Here, we review recent advances in computational models, in parallel with an expansion of the molecular toolbox, in the pursuit of optimal host strains for industrial protein production. PMID:23892981

Royle, Kate; Kontoravdi, Cleo

2013-12-01

306

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

Microsoft Academic Search

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

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

2010-01-01

307

Biological Nitrogen Fixation in Relation to Energy Forest Production. Progress Report, 1978-1980.  

National Technical Information Service (NTIS)

Different pasture legumes, Alnus incana and Myrica gale have been tested in pot experiments and field trials with respect to their use as biological N-fertilizers in relation to energy forest production. So far experiments have been mainly concerned with ...

M. Clarholm U. Granhall

1981-01-01

308

The Use of Video in Transferable Skills Education for Biology Students I. Production of Pilot Videos  

Microsoft Academic Search

Students in the penultimate year of a Biology degree produced pilot videos on microbiological topics using camcorders. Videos were intended for use as school teaching aids: the ‘best’ video was selected for subsequent professional production. The organisation, assessment and evaluation of the project are described.

Joanna Verran

1992-01-01

309

The Analysis of Cyanide and its Breakdown Products in Biological Samples  

Microsoft Academic Search

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

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

2010-01-01

310

The chemistry of suspended matter in Esthwaite Water, a biologically productive lake with seasonally anoxic hypolimnion  

Microsoft Academic Search

Ten detailed vertical water column profiles were taken between April and November, 1979, in Esthwaite Water (English Lake district), a lake with high biological productivity and a seasonally anoxic hypolimnion. Measurements of the major-element particle composition (organic C, P, S, Si, Al, Ti, K, Mg, Ca, Fe, Mn, and Ba) and hydrochemical constituents (temperature, pH, dissolved oxygen, total suspended load,

Edward R. Sholkovitz; David Copland

1982-01-01

311

HPLC study of oxidation products of hydroethidine in chemical and biological systems: ramifications in superoxide measurements  

Microsoft Academic Search

Methods for the detection and quantitation of hydroethidine (HE) and its oxidation products by HPLC analysis are described. Synthetic methods for preparation of authentic standards (2-hydroxyethidium and diethidium) are provided. Potential applications of the HPLC methods to chemical and biological systems are discussed. Specific examples of chromatograms obtained using UV–Vis absorption, fluorescence, electrochemical, and mass spectrometry detectors are provided. The

Jacek Zielonka; Micael Hardy; B. Kalyanaraman

2009-01-01

312

Recent advances in the production of proteins in insect and mammalian cells for structural biology  

Microsoft Academic Search

The production of proteins in sufficient quantity and of appropriate quality is an essential pre-requisite for structural studies. Escherichia coli remains the dominant expression system in structural biology with nearly 90% of the structures in the Protein Data Bank (PDB) derived from proteins produced in this bacterial host. However, many mammalian and eukaryotic viral proteins require post-translation modification for proper

Joanne E. Nettleship; René Assenberg; Jonathan M. Diprose; Nahid Rahman-Huq; Raymond J. Owens

2010-01-01

313

The case for vaccines.  

PubMed

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

Hoffman, Wendell W

2013-01-01

314

Potency assays for therapeutic live whole cell cancer vaccines.  

PubMed

Therapeutic cancer vaccines are under development with the goal of enhancing the body's immune response to cancer cells sufficient to arrest cancer cell growth. Among the various approaches being used are those based on whole tumor cells. Developing a suitable measure of the potency of such vaccines presents a significant challenge because neither cellular associated markers nor in vivo biological responses that are correlated with efficacy have been identified; nevertheless, manufacturers and regulatory agencies will need to develop methods to evaluate these products. At this moment, the challenge for manufacturers who are developing whole cell vaccines is to demonstrate batch-to-batch consistency for the vaccine used in clinical studies and to show that comparable vaccine batches have the same capacity to achieve an acceptable level of biological activity that may be related to efficacy. This is particularly challenging in that animal models to test that activity do not exist and direct serological or immunological correlates of clinical protection are not available because protection has not yet been established in clinical trials. In the absence of well-defined biological markers and tests for manufacturing consistency, manufacturers and regulators will need to rely heavily on a highly reproducible manufacturing process--the consistency of the process therefore becomes critical. In developing regulatory approaches to whole cell cancer vaccines, the experience from the field of infectious disease vaccines should be examined for general guidance. A framework that draws heavily on the field of infectious disease vaccines is presented and suggests that at this point in the development of this new class of products, it is reasonable to develop data on quantitative antigen expression as a measure of potency with the expectation that when clinical efficacy has been established it will confirm the appropriateness of this approach. But because this will not be known until the end of a pivotal trial, a bioassay should be considered and run in parallel. Several examples of bioassays are presented along with their advantages and disadvantages. The final selection of a potency assay for use in lot release of a commercializable therapeutic whole cell vaccine ultimately will depend on the totality of the data available at the time of approval by regulatory agencies. Based on information currently available, it is likely that quantitative antigen expression or a bioassay could be used to measure potency. If both are determined to be acceptable, the use of quantitative antigen expression could be considered for routine lot release, while the bioassay could be reserved for use as one of the elements in establishing comparability when manufacturing changes are being considered after approval. PMID:16882459

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

2007-04-01

315

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

PubMed

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

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

2013-11-01

316

Nanoparticles for transcutaneous vaccination.  

PubMed

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

Hansen, Steffi; Lehr, Claus-Michael

2012-03-01

317

Nanoparticles for transcutaneous vaccination  

PubMed Central

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

Hansen, Steffi; Lehr, Claus-Michael

2012-01-01

318

Rapid Production of Specific Vaccines for Lymphoma by Expression of the Tumor-Derived Single-Chain Fv Epitopes in Tobacco Plants  

Microsoft Academic Search

Rapid production of protein-based tumor-specific vaccines for the treatment of malignancies is possible with the plant-based transient expression system described here. We created a modified tobamoviral vector that encodes the idiotype-specific single-chain Fv fragment (scFv) of the immunoglobulin from the 38C13 mouse B cell lymphoma. Infected Nicotiana benthamiana plants contain high levels of secreted scFv protein in the extracellular compartment.

Alison A. McCormick; Monto H. Kumagai; Kathleen Hanley; Thomas H. Turpen; Itzhak Hakim; Laurence K. Grill; Daniel Tuse; Shoshana Levy; Ronald Levy

1999-01-01

319

Statistical and regulatory considerations in assessments of interchangeability of biological drug products.  

PubMed

When the patent of a brand-name, marketed drug expires, new, generic products are usually offered. Small-molecule generic and originator drug products are expected to be chemically identical. Their pharmaceutical similarity can be typically assessed by simple regulatory criteria such as the expectation that the 90% confidence interval for the ratio of geometric means of some pharmacokinetic parameters be between 0.80 and 1.25. When such criteria are satisfied, the drug products are generally considered to exhibit therapeutic equivalence. They are then usually interchanged freely within individual patients. Biological drugs are complex proteins, for instance, because of their large size, intricate structure, sensitivity to environmental conditions, difficult manufacturing procedures, and the possibility of immunogenicity. Generic and brand-name biologic products can be expected to show only similarity but not identity in their various features and clinical effects. Consequently, the determination of biosimilarity is also a complicated process which involves assessment of the totality of the evidence for the close similarity of the two products. Moreover, even when biosimilarity has been established, it may not be assumed that the two biosimilar products can be automatically substituted by pharmacists. This generally requires additional, careful considerations. Without declaring interchangeability, a new product could be prescribed, i.e. it is prescribable. However, two products can be automatically substituted only if they are interchangeable. Interchangeability is a statistical term and it means that products can be used in any order in the same patient without considering the treatment history. The concepts of interchangeability and prescribability have been widely discussed in the past but only in relation to small molecule generics. In this paper we apply these concepts to biosimilars and we discuss: definitions of prescribability and interchangeability and their statistical implementation; the relation between bioequivalence and interchangeability for small-molecule drug products; regulatory requirements and expectations of biosimilar products in various jurisdictions; possible statistical approaches to establish the similarity and interchangeability of biologic drug products; definition of other technical terms such as switchability and automatic substitution. The paper will be concluded with a discussion of the anticipated future use of interchangeability of biological drug products. PMID:24832831

Tóthfalusi, Lászlo; Endrényi, László; Chow, Shein-Chung

2014-05-01

320

A purified inactivated Japanese encephalitis virus vaccine made in vero cells  

Microsoft Academic Search

A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals.

Ashok K. Srivastava; J. Robert Putnak; Sung H. Lee; Sun P. Hong; Sang B. Moon; David A. Barvir; Bangti Zhao; Russell A. Olson; Soo-Ok Kim; Wang-Don Yoo; Andrew C. Towle; David W. Vaughn; Bruce L. Innis; Kenneth H. Eckels

2001-01-01

321

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

ERIC Educational Resources Information Center

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

Guilfoile, Patrick

1999-01-01

322

Plant-based production of recombinant Plasmodium surface protein pf38 and evaluation of its potential as a vaccine candidate.  

PubMed

Pf38 is a surface protein of the malarial parasite Plasmodium falciparum. In this study, we produced and purified recombinant Pf38 and a fusion protein composed of red fluorescent protein and Pf38 (RFP-Pf38) using a transient expression system in the plant Nicotiana benthamiana. To our knowledge, this is the first description of the production of recombinant Pf38. To verify the quality of the recombinant Pf38, plasma from semi-immune African donors was used to confirm specific binding to Pf38. ELISA measurements revealed that immune responses to Pf38 in this African subset were comparable to reactivities to AMA-1 and MSP119. Pf38 and RFP-Pf38 were successfully used to immunise mice, although titres from these mice were low (on average 1?11.000 and 1?39.000, respectively). In immune fluorescence assays, the purified IgG fraction from the sera of immunised mice recognised Pf38 on the surface of schizonts, gametocytes, macrogametes and zygotes, but not sporozoites. Growth inhibition assays using ?Pf38 antibodies demonstrated strong inhibition (?60%) of the growth of blood-stage P. falciparum. The development of zygotes was also effectively inhibited by ?Pf38 antibodies, as determined by the zygote development assay. Collectively, these results suggest that Pf38 is an interesting candidate for the development of a malaria vaccine. PMID:24278216

Feller, Tatjana; Thom, Pascal; Koch, Natalie; Spiegel, Holger; Addai-Mensah, Otchere; Fischer, Rainer; Reimann, Andreas; Pradel, Gabriele; Fendel, Rolf; Schillberg, Stefan; Scheuermayer, Matthias; Schinkel, Helga

2013-01-01

323

Catecholamine plasma levels, IFN-? serum levels and antibodies production induced by rabies vaccine in dogs selected for their paw preference.  

PubMed

To explore the possible role of the sympathetic nervous activity in the asymmetrical crosstalk between the brain and immune system, catecholamine (E, NE) plasma levels, Interferon-? (IFN-?) serum levels and production of antibodies induced by rabies vaccine in dogs selected for their paw preference were measured. The results showed that the direction of behavioural lateralization influenced both epinephrine levels and immune response in dogs. A different kinetic of epinephrine levels after immunization was observed in left-pawed dogs compared to both right-pawed and ambidextrous dogs. The titers of antirabies antibodies were lower in left-pawed dogs than in right-pawed and ambidextrous dogs. Similarly, the IFN-? serum levels were lower in left-pawed dogs than in the other two groups. Taken together, these findings showed that the left-pawed group appeared to be consistently the different group stressing the fundamental role played by the sympathetic nervous system as a mechanistic basis for the crosstalk between the brain and the immune system. PMID:24364988

Siniscalchi, Marcello; Cirone, Francesco; Guaricci, Antonio Ciro; Quaranta, Angelo

2014-09-01

324

Smallpox Vaccines for Biodefense  

PubMed Central

Few diseases can match the enormous impact that smallpox has had on mankind. Its influence can be seen in the earliest recorded histories of ancient civilizations in Egypt and Mesopotamia. With fatality rates up to 30%, smallpox left its survivors with extensive scarring and other serious sequelae. It is estimated that smallpox killed 500 million people in the 19th and 20th centuries. Given the ongoing concerns regarding the use of variola as a biological weapon, this review will focus on the licensed vaccines as well as current research into next-generation vaccines to protect against smallpox and other poxviruses.

Kennedy, Richard B.; Ovsyannikova, Inna; Poland, Gregory A.

2009-01-01

325

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

NASA Astrophysics Data System (ADS)

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

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

326

Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01_AE, and CRF02_AG, for the Development and Assessment of Candidate Vaccines  

PubMed Central

A critical priority for human immunodeficiency virus type 1 (HIV-1) vaccine development is standardization of reagents and assays for evaluation of immune responses elicited by candidate vaccines. To provide a panel of viral reagents from multiple vaccine trial sites, 60 international HIV-1 isolates were expanded in peripheral blood mononuclear cells and characterized both genetically and biologically. Ten isolates each from clades A, B, C, and D and 10 isolates each from CRF01_AE and CRF02_AG were prepared from individuals whose HIV-1 infection was evaluated by complete genome sequencing. The main criterion for selection was that the candidate isolate was pure clade or pure circulating recombinant. After expansion in culture, the complete envelope (gp160) of each isolate was verified by sequencing. The 50% tissue culture infectious dose and p24 antigen concentration for each viral stock were determined; no correlation between these two biologic parameters was found. Syncytium formation in MT-2 cells and CCR5 or CXCR4 coreceptor usage were determined for all isolates. Isolates were also screened for neutralization by soluble CD4, a cocktail of monoclonal antibodies, and a pool of HIV-1-positive patient sera. The panel consists of 49 nonsyncytium-inducing isolates that use CCR5 as a major coreceptor and 11 syncytium-inducing isolates that use only CXCR4 or both coreceptors. Neutralization profiles suggest that the panel contains both neutralization-sensitive and -resistant isolates. This collection of HIV-1 isolates represents the six major globally prevalent strains, is exceptionally large and well characterized, and provides an important resource for standardization of immunogenicity assessment in HIV-1 vaccine trials.

Brown, Bruce K.; Darden, Janice M.; Tovanabutra, Sodsai; Oblander, Tamara; Frost, Julie; Sanders-Buell, Eric; de Souza, Mark S.; Birx, Deborah L.; McCutchan, Francine E.; Polonis, Victoria R.

2005-01-01

327

Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG, for the development and assessment of candidate vaccines.  

PubMed

A critical priority for human immunodeficiency virus type 1 (HIV-1) vaccine development is standardization of reagents and assays for evaluation of immune responses elicited by candidate vaccines. To provide a panel of viral reagents from multiple vaccine trial sites, 60 international HIV-1 isolates were expanded in peripheral blood mononuclear cells and characterized both genetically and biologically. Ten isolates each from clades A, B, C, and D and 10 isolates each from CRF01_AE and CRF02_AG were prepared from individuals whose HIV-1 infection was evaluated by complete genome sequencing. The main criterion for selection was that the candidate isolate was pure clade or pure circulating recombinant. After expansion in culture, the complete envelope (gp160) of each isolate was verified by sequencing. The 50% tissue culture infectious dose and p24 antigen concentration for each viral stock were determined; no correlation between these two biologic parameters was found. Syncytium formation in MT-2 cells and CCR5 or CXCR4 coreceptor usage were determined for all isolates. Isolates were also screened for neutralization by soluble CD4, a cocktail of monoclonal antibodies, and a pool of HIV-1-positive patient sera. The panel consists of 49 nonsyncytium-inducing isolates that use CCR5 as a major coreceptor and 11 syncytium-inducing isolates that use only CXCR4 or both coreceptors. Neutralization profiles suggest that the panel contains both neutralization-sensitive and -resistant isolates. This collection of HIV-1 isolates represents the six major globally prevalent strains, is exceptionally large and well characterized, and provides an important resource for standardization of immunogenicity assessment in HIV-1 vaccine trials. PMID:15857994

Brown, Bruce K; Darden, Janice M; Tovanabutra, Sodsai; Oblander, Tamara; Frost, Julie; Sanders-Buell, Eric; de Souza, Mark S; Birx, Deborah L; McCutchan, Francine E; Polonis, Victoria R

2005-05-01

328

A downstream process for production of a viable and stable Bacillus cereus aquaculture biological agent.  

PubMed

Biological products offer advantages over chemotherapeutics in aquaculture. Adoption in commercial application is lacking due to limitations in process and product development that address key end user product requirements such as cost, efficacy, shelf life and convenience. In previous studies, we have reported on the efficacy, physiological robustness and low-cost spore production of a Bacillus cereus isolate (NRRL 100132). This study examines the development of suitable spore recovery, drying, formulation and tablet production from the fermentation product. Key criteria used for such downstream process unit evaluation included spore viability, recovery, spore balance, spore re-germination, product intermediate stability, end product stability and efficacy. A process flow sheet comprising vertical tube centrifugation, fluidised bed agglomeration and tablet pressing yielded a suitable product. The formulation included corn steep liquor and glucose to enhance subsequent spore regermination. Viable spore recovery and spore balance closure across each of the process units was high (>70% and >99% respectively), with improvement in recovery possible by adoption of continuous processing at large scale. Spore regermination was 97%, whilst a product half-life in excess of 5 years was estimated based on thermal resistance curves. The process resulted in a commercially attractive product and suitable variable cost of production. PMID:19921182

Lalloo, Rajesh; Maharajh, Dheepak; Görgens, Johann; Gardiner, Neil

2010-03-01

329

What controls biological productivity in coastal upwelling systems? Insights from a comparative modeling study  

NASA Astrophysics Data System (ADS)

The magnitude of the biological productivity in Eastern Boundary Upwelling Systems (EBUS) is traditionally viewed as directly reflecting the upwelling intensity. Yet, different EBUS show different sensitivities of productivity to upwelling-favorable winds (Carr and Kearns, 2003). Here, using a comparative modeling study of the California Current System (California CS) and Canary Current System (Canary CS), we show how physical and environmental factors, such as light, temperature and cross-shore circulation modulate the response of biological productivity to upwelling strength. To this end, we made a series of eddy-resolving simulations of the California CS and Canary CS using the Regional Ocean Modeling System (ROMS), coupled to a nitrogen based Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD) ecosystem model. We find the nutrient content of the euphotic zone to be 20 % smaller in the Canary CS relative to the California CS. Yet, the biological productivity is 50 % smaller in the latter. This is due to: (1) a faster nutrient-replete growth in the Canary CS relative to the California CS, related to a more favorable light and temperature conditions in the Canary CS, and (2) the longer nearshore water residence times in the Canary CS which lead to larger buildup of biomass in the upwelling zone, thereby enhancing the productivity. The longer residence times in the Canary CS appear to be associated with the wider continental shelves and the lower eddy activity characterizing this upwelling system. This results in a weaker offshore export of nutrients and organic matter, thereby increasing local nutrient recycling and enhancing the coupling between new and export production in the Northwest African system. Our results suggest that climate change induced perturbations such as upwelling favorable wind intensification might lead to contrasting biological responses in the California CS and the Canary CS, with major implications for the biogeochemical cycles and fisheries in these two ecosystems.

Lachkar, Z.; Gruber, N.

2011-06-01

330

Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses  

PubMed Central

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

Mooney, Alaina J; Tompkins, S Mark

2013-01-01

331

Bovine respiratory disease: commercial vaccines currently available in Canada.  

PubMed Central

Bovine respiratory disease (BRD) remains a significant cost to both the beef and dairy industries. In the United States, an estimated 640 million dollars is lost annually due to BRD. Losses are largely a result of pneumonic pasteurellosis ("shipping fever"), enzootic pneumonia of calves, and atypical interstitial pneumonia. In Canada, over 80% of the biologics licensed for use in cattle are against agents associated with BRD. The objectives of this paper were (a) to summarize information available concerning commercial vaccines currently used in Canada for protection against BRD, and (b) to provide an easily accessible resource for veterinary practitioners and researchers. Information from the most recent Compendium of Veterinary Products has been tabulated for each vaccine by trade name, according to vaccine type, and the pathogens against which they are designed to protect. Additional information from published articles (peer-reviewed and other) has been provided and referenced.

Bowland, S L; Shewen, P E

2000-01-01

332

Prospective cost-benefit analysis of a two-dimensional barcode for vaccine production, clinical documentation, and public health reporting and tracking.  

PubMed

In the United States recording accurate vaccine lot numbers in immunization records is required by the National Childhood Vaccine Injury Act and is necessary for public health surveillance and implementation of vaccine product recalls. However, this information is often missing or inaccurate in records. The Food and Drug Administration (FDA) requires a linear barcode of the National Drug Code (NDC) on vaccine product labels as a medication verification measure, but lot number and expiration date must still be recorded by hand. Beginning in 2011, FDA permitted manufacturers to replace linear barcodes with two-dimensional (2D) barcodes on unit-of-use product labels. A 2D barcode can contain the NDC, expiration date, and lot number in a symbol small enough to fit on a unit-of-use label. All three data elements could be scanned into a patient record. To assess 2D barcodes' potential impacts, a mixed-methods approach of time-motion data analysis, interview and survey data collection, and cost-benefit analysis was employed. Analysis of a time-motion study conducted at 33 practices suggests scanning 2D-barcoded vaccines could reduce immunization documentation time by 36-39 s per dose. Data from an internet survey of primary care providers and local health officials indicate that 60% of pediatric practices, 54% of family medicine practices, and 39% of health departments would use the 2D barcode, with more indicating they would do so if they used electronic health records. Inclusive of manufacturer and immunization provider costs and benefits, we forecast lower-bound net benefits to be $310-334 million between 2011 and 2023 with a benefit-to-cost ratio of 3.1:1-3.2:1. Although we were unable to monetize benefits for expected improved immunization coverage, surveillance, or reduced medication errors, based on our findings, we expect that using 2D barcodes will lower vaccine documentation costs, facilitate data capture, and enhance immunization data quality. PMID:23664988

O'Connor, Alan C; Kennedy, Erin D; Loomis, Ross J; Haque, Saira N; Layton, Christine M; Williams, Warren W; Amoozegar, Jacqueline B; Braun, Fern M; Honeycutt, Amanda A; Weinbaum, Cindy

2013-06-28

333

Future of Polio Vaccines  

PubMed Central

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

2009-01-01

334

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

ClinicalTrials.gov

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

2012-11-16

335

Plant-derived virus-like particles as vaccines.  

PubMed

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

Chen, Qiang; Lai, Huafang

2013-01-01

336

Production, characterization and control of a Neisseria meningitidis hexavalent class 1 outer membrane protein containing vesicle vaccine.  

PubMed

An experimental serogroup B meningococcal vaccine was prepared from two genetically engineered strains; each expressing three different class 1 outer membrane proteins (OMPs) (PorA). The two strains expressed the subtypes P1.7,16;P1.5,2;P1.19,15 and P1.5c,10;P1.12,13;P1.7h,4, respectively. Outer membrane vesicles (OMV) were prepared from these strains by deoxycholate extraction, mixed with aluminiumphosphate as adjuvant and formulated to final vaccines. The class 1 OMPs represent ca 90% of the protein in the vaccine. The vaccine was found safe for human use and induced a bactericidal immune response in mice against five of the six wild type strains, which served as donors for the various por A genes. PMID:8873395

Claassen, I; Meylis, J; van der Ley, P; Peeters, C; Brons, H; Robert, J; Borsboom, D; van der Ark, A; van Straaten, I; Roholl, P; Kuipers, B; Poolman, J

1996-07-01

337

Induction of Dendritic Cell Production of Type I and Type III Interferons by Wild-Type and Vaccine Strains of Measles Virus: Role of Defective Interfering RNAs  

PubMed Central

The innate immune response to viral infection frequently includes induction of type I interferons (IFN), but many viruses have evolved ways to block this response and increase virulence. In vitro studies of IFN production after infection of susceptible cells with measles virus (MeV) have often reported greater IFN synthesis after infection with vaccine than with wild-type strains of MeV. However, the possible presence in laboratory virus stocks of 5? copy-back defective interfering (DI) RNAs that induce IFN independent of the standard virus has frequently confounded interpretation of data from these studies. To further investigate MeV strain-dependent differences in IFN induction and the role of DI RNAs, monocyte-derived dendritic cells (moDCs) were infected with the wild-type Bilthoven strain and the vaccine Edmonston-Zagreb strain with and without DI RNAs. Production of type I IFN, type III IFN, and the interferon-stimulated genes (ISGs) Mx and ISG56 by infected cells was assessed with a flow cytometry-based IFN bioassay, quantitative reverse transcriptase PCR (RT-PCR), and immunoassays. Bilthoven infected moDCs less efficiently than Edmonston-Zagreb. Presence of DI RNAs in vaccine stocks resulted in greater maturation of moDCs, inhibition of virus replication, and induction of higher levels of IFN and ISGs. Production of type I IFN, type III IFN, and ISG mRNA and protein was determined by both the level of infection and the presence of DI RNAs. At the same levels of infection and in the absence of DI RNA, IFN induction was similar between wild-type and vaccine strains of MeV.

Shivakoti, Rupak; Siwek, Martina; Hauer, Debra; Schultz, Kimberly L. W.

2013-01-01

338

Relationship between HLA Polymorphisms and Gamma Interferon and Interleukin10 Cytokine Production in Healthy Individuals after Rubella Vaccination  

Microsoft Academic Search

We studied the association between HLA alleles and rubella-specific gamma interferon (IFN-) (Th1) and interleukin-10 (IL-10) (Th2) cytokine responses among 106 healthy children (ages, 14 to 17 years) previously immunized with two doses of rubella vaccine. Antibody titers and cytokine responses to rubella vaccination were not sex or age dependent. Several class I HLA-A (*0201, *2402, *6801) alleles were significantly

Inna G. Ovsyannikova; Robert M. Jacobson; Jenna E. Ryan; Neelam Dhiman; Robert A. Vierkant; Gregory A. Poland

2007-01-01

339

Anti-endotoxin vaccines  

PubMed Central

Gram-negative bacterial (GNB) infections are a leading cause of serious infections both in hospitals and the community. The mortality remains high despite potent antimicrobials and modern supportive care. In the last decade invasive GNB have become increasingly resistant to commonly used antibiotics, and attempts to intervene with novel biological therapies have been unsuccessful. Earlier studies with antibodies directed against a highly conserved core region in the GNB lipopolysaccharide (LPS, or endotoxin) suggested that this approach may have therapeutic benefit, and led to the development of a subunit vaccine that has progressed to phase 1 clinical testing. Since only a few serogroups of GNB cause bacteremia, O-specific vaccines had been developed, but these were not deployed because of the availability of other therapeutic options at the time. Given the likelihood that new antibiotics will not be soon available, the development of vaccines and antibodies directed against endotoxin, both O and core antigens, deserves a “second look”.

Cross, Alan S

2014-01-01

340

Baculovirus as vaccine vectors.  

PubMed

Application of viral vectors derived from human viruses to mediate immune response in animals and humans has been greatly hampered by the problems associated with pre-existing immunity and associated toxicities. Among few non-human viral vectors, baculovirus has now evolved as a novel tool for vaccine vector development. With broad tissue tropism and expanded bio-safety profile suitably supplemented with intrinsic immunostimulatory properties, baculovirus has now attained a niche position in the arena of vaccine development. Recombinant envelope-modified baculovirus equipped with novel shuttle promoters for in vivo transduction has shown promising results in several animal models. Baculovirus mediated induction of systemic and mucosal immune responses through intranasal or oral administration has now open an entirely new way for the development of new generation vaccines. Gaining additional insight into the baculovirus biology and its interaction with non-native hosts will certainly promote this human-friendly virus as a potential vector for clinical applications. PMID:20394572

Madhan, Selvaraj; Prabakaran, Mookkan; Kwang, Jimmy

2010-06-01

341

Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers  

Microsoft Academic Search

In 14 clinical studies, various efficacy and safety aspects of a new virosomal influenza vaccine (Invivac®) were assessed in 2865 subjects. The virosomal influenza vaccine fully complies with the Committee for Proprietary Medicinal Products (CPMP) requirement for immunogenicity of influenza vaccines. In particular, in a subset of subjects with low pre-vaccination titers (thus those persons who actually need protection by

I. A de Bruijn; J Nauta; L Gerez; A. M Palache

2004-01-01

342

Viral vectors for vaccine applications  

PubMed Central

Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the reduction and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral molecular biology and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast number of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense.

Choi, Youngjoo

2013-01-01

343

Viral vectors for vaccine applications.  

PubMed

Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the reduction and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral molecular biology and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast number of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense. PMID:23858400

Choi, Youngjoo; Chang, Jun

2013-07-01

344

Effect of Mycobacterium bovis BCG Vaccination on Mycobacterium-Specific Cellular Proliferation and Tumor Necrosis Factor Alpha Production from Distinct Guinea Pig Leukocyte Populations  

PubMed Central

In this study, we focused on three leukocyte-rich guinea pig cell populations, bronchoalveolar lavage (BAL) cells, resident peritoneal cells (PC), and splenocytes (SPC). BAL cells, SPC, and PC were stimulated either with live attenuated Mycobacterium tuberculosis H37Ra or with live or heat-killed virulent M. tuberculosis H37Rv (multiplicity of infection of 1:100). Each cell population was determined to proliferate in response to heat-killed virulent H37Rv, whereas no measurable proliferative response could be detected upon stimulation with live mycobacteria. Additionally, this proliferative capacity (in SPC and PC populations) was significantly enhanced upon prior vaccination with Mycobacterium bovis BCG. Accordingly, in a parallel set of experiments we found a strong positive correlation between production of antigen-specific bioactive tumor necrosis factor alpha (TNF-?) and prior vaccination with BCG. A nonspecific stimulus, lipopolysaccharide, failed to induce this effect on BAL cells, SPC, and PC. These results showed that production of bioactive TNF-? from mycobacterium-stimulated guinea pig cell cultures positively correlates with the vaccination status of the host and with the virulence of the mycobacterial strain.

Lasco, Todd M.; Yamamoto, Toshiko; Yoshimura, Teizo; Allen, Shannon Sedberry; Cassone, Lynne; McMurray, David N.

2003-01-01

345

Chemical and biological evaluation of endotoxin contamination on natural rubber latex products.  

PubMed

Relationship between pyrogenicity and bacterial endotoxin contamination on latex products was demonstrated by chemical analysis and biological assays. In commercially available latex products' surveillance, water extracts prepared from one surgical glove and two silicone elastomer-coated Foley catheters sterilized by gamma-irradiation were obviously pyrogenic in rabbits. The induced fever was monophasic at low dose of the pyrogenic extracts and biphasic at high dose. These extracts exhibited limulus amebocyte lysate gelation activity, and induced inflammatory cytokine (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) production from MM6-CA8 human monocytoid cells. These biological properties, including pyrogenicity, completely disappeared by treating the pyrogenic extracts with endotoxin-adsorbent affinity column. Limulus amebocyte lysate activity and cytokine production from MM6-CA8 cells induced by the extracts were significantly decreased by endotoxin inhibitors, an active fragment peptide of an 18-kDa cationic antimicrobial protein and a synthetic lipid A B464 analogue. Furthermore, very small amounts of 2-keto-3-deoxyoctonate and 3-hydroxy fatty acid, which are common constituents of bacterial endotoxins, were detected by gas chromatography-mass spectrometry analysis of the pyrogenic extracts. These findings clearly showed that the pyrogenicity found in these latex products originated from endotoxins contaminating the products. PMID:11255197

Haishima, Y; Murai, T; Nakagawa, Y; Hirata, M; Yagami, T; Nakamura, A

2001-06-01

346

Vaccines against bluetongue in Europe  

Microsoft Academic Search

After the incursion of bluetongue virus (BTV) into European Mediterranean countries in 1998, vaccination was used in an effort to minimize direct economic losses to animal production, reduce virus circulation and allow safe movements of animals from endemic areas. Vaccination strategies in different countries were developed according to their individual policies, the geographic distribution of the incurring serotypes of BTV

Giovanni Savini; N. James MacLachlan; Jose-Manuel Sanchez-Vizcaino; Stéphan Zientara

2008-01-01

347

Seasonal influenza vaccination and technologies.  

PubMed

Seasonal influenza is a serious respiratory illness that causes annual worldwide epidemics resulting in significant morbidity and mortality. Influenza pandemics occur about every 40 yrs, and may carry a greater burden of illness and death than seasonal influenza. Both seasonal influenza and pandemic influenza have profound economic consequences. The combination of current vaccine efficacy and viral antigenic drifts and shifts necessitates annual vaccination. New manufacturing technologies in influenza vaccine development employ cell culture and recombinant techniques. Both allow more rapid vaccine creation and production. In the past 5 years, brisk, highly creative activity in influenza vaccine research and development has begun. New vaccine technologies and vaccination strategies are addressing the need for viable alternatives to egg production methods and improved efficacy. At present, stubborn problems of sub-optimal efficacy and the need for annual immunization persist. There is an obvious need for more efficacious vaccines and improved vaccination strategies to make immunization easier for providers and patients. Mitigating this serious annual health threat remains an important public health priority. PMID:24691877

Nafziger, Anne N; Pratt, David S

2014-07-01

348

Advances in antiviral vaccine development.  

PubMed

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

Graham, Barney S

2013-09-01

349

Recombinant vaccines.  

PubMed

The Recombinant Vaccines: Strategies for Candidate Discovery and Vaccine Delivery conference, organized by EuroSciCon, hosted a group of UK-based and international scientists from as far afield as Malaysia and Australia. Genomic analyses of pathogens and elucidation of mechanisms of pathogenesis has advanced candidate discovery and development of vaccines. Therefore, it was timely that this conference featured, in addition to detailed expositions of target selection and clinical trials, presentations on manufacturability, scale-up and delivery of vaccines. Ten talks were presented. This meeting report describes the key topics presented and the themes that emerged from this conference. PMID:20450319

Barnard, Ross Thomas

2010-05-01

350

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

PubMed

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

Ferrari, Luca; Borghetti, Paolo; De Angelis, Elena; Martelli, Paolo

2014-01-01

351

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

PubMed Central

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

2014-01-01

352

Biogas production and valorization by means of a two-step biological process  

Microsoft Academic Search

The scope of this research work was to investigate biogas production and purification by a two-step bench-scale biological system, consisting of fed-batch pulse-feeding anaerobic digestion of mixed sludge, followed by methane enrichment of biogas by the use of the cyanobacterium Arthrospiraplatensis. The composition of biogas was nearly constant, and methane and carbon dioxide percentages ranged between 70.5–76.0% and 13.2–19.5%, respectively.

A. Converti; R. P. S. Oliveira; B. R. Torres; A. Lodi; M. Zilli

2009-01-01

353

Biological nitrogen fixation and socioeconomic factors for legume production in sub-Saharan Africa: a review  

Microsoft Academic Search

Low crop productivity is a general problem facing most farming systems in sub-Saharan Africa (SSA). These low yields are pronounced\\u000a in grain legumes and are often associated with declining soil fertility and reduced N2-fixation due to biological and environmental factors. Unfortunately, the majority of African small farmers are now unable\\u000a to afford the high mineral fertilizer prices. More than 75%

Jonas. N. Chianu; E. M. Nkonya; F. S. Mairura; Justina. N. Chianu; F. K. Akinnifesi

2011-01-01

354

antiTuberculosis natural products: synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin  

Microsoft Academic Search

There is an urgent need for novel therapeutics possessing new modes of action to treat tuberculosis (TB) infections. In this study we report on the synthesis and biological evaluation of a series of pyrido[2,3,4-kl]acridin-6-one alkaloids related to the anti-TB (MIC 0.35?M) but cytotoxic (IC50 <0.14?M) marine natural product ascididemin (1). The most interesting compounds identified were 21 and 24, which

David R. Appleton; A. Norrie Pearce; Brent R. Copp

2010-01-01

355

Tick-borne Encephalitis Vaccines  

PubMed Central

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

Lehrer, Axel T; Holbrook, Michael R.

2012-01-01

356

Activity and biological effects of neem products against arthropods of medical and veterinary importance.  

PubMed

Botanical insecticides are relatively safe and degradable, and are readily available sources of biopesticides. The most prominent phytochemical pesticides in recent years are those derived from neem trees, which have been studied extensively in the fields of entomology and phytochemistry, and have uses for medicinal and cosmetic purposes. The neem products have been obtained from several species of neem trees in the family Meliaceae. Six species in this family have been the subject of botanical pesticide research. They are Azadirachta indica A. Juss, Azadirachta excelsa Jack, Azadirachta siamens Valeton, Melia azedarach L., Melia toosendan Sieb. and Zucc., and Melia volkensii Gürke. The Meliaceae, especially A. indica (Indian neem tree), contains at least 35 biologically active principles. Azadirachtin is the predominant insecticidal active ingredient in the seed, leaves, and other parts of the neem tree. Azadirachtin and other compounds in neem products exhibit various modes of action against insects such as antifeedancy, growth regulation, fecundity suppression and sterilization, oviposition repellency or attractancy, changes in biological fitness, and blocking development of vector-borne pathogens. Some of these bioactivity parameters of neem products have been investigated at least in some species of insects of medical and veterinary importance, such as mosquitoes, flies, triatomines, cockroaches, fleas, lice, and others. Here we review, synthesize, and analyze published information on the activity, modes of action, and other biological effects of neem products against arthropods of medical and veterinary importance. The amount of information on the activity, use, and application of neem products for the control of disease vectors and human and animal pests is limited. Additional research is needed to determine the potential usefulness of neem products in vector control programs. PMID:10412110

Mulla, M S; Su, T

1999-06-01

357

Overview of cancer vaccines  

PubMed Central

Cancer immunotherapy has seen a tremendous number of failures and only few recent regulatory successes. This is a review dedicated to determine major regulatory and developmental issues around cancer immunotherapeutics. A three pillar approach should be used in setting a development path: discovery platforms and sufficient pool of validated tumor antigens, product development strategy enabling to bring the product closer to the patient and clinical development strategy accounting for competitive landscape, treatment paradigm, technical and commercial risks. Regulatory framework existing around cancer vaccines in the EU, US, Japan and some developing countries is outlined. In addition, the review covers some specific issues on the design and conduct of clinical trials with cancer vaccines.

Kudrin, Alex

2012-01-01

358

Biological Productivity from an Oxygen Mass Balance in the subarctic North Pacific  

NASA Astrophysics Data System (ADS)

Biological productivity is an important process controlling the export of carbon into the deep ocean and thus influencing the earth's climate. An O2 mass balance of the upper ocean can estimate this export of organic carbon if the physical processes affecting the O2 concentrations are accounted for. This can be accomplished by measuring the dissolved O2/Ar ratio, because their similar physical properties allow us to consider Ar an 'abiotic' O2 analogue. Here we present a two-year data set of O2/N2/Ar ratio measurements collected at Station Papa and along Line P in 2007/08. Line P, situated in the subarctic North Pacific, is a series of oceanographic stations running from the southwest tip of Vancouver Island to Station Papa (50°N, 145°W), one of the oldest deep-ocean time series in existence which is located in the High-Nutrient/Low-Chlorophyll (HNLC) region of the subarctic gyre. Current cruises along Line P run three times per year, typically in February, June and August. The dissolved gas ratios are measured using a stable isotope mass spectrometer and oxygen concentrations by titration. In a simple steady state, we equate biological O2 production to diffusive gas exchange, using the O2/Ar ratio to normalize the physical component of the oxygen signal and calculate the net biological oxygen production. Diffusive gas exchange is calculated using a wind speed parameterization. Preliminary estimates of the net biological production in the mixed layer at Station Papa for 2007 are calculated at 30.9 and 14.0 mmol C m-2 d- 1 for June and August respectively, both exhibiting mixed layer O2/Ar supersaturations. The O2/Ar undersaturation in the mixed layer for February 2007 suggests net respiration at that time. The wind speed parameterization of diffusive gas exchange is the major source of error for this method. We plan to refine our productivity calculation to account for vertical mixing and also by measuring rates of production using a number of different methods, so that we may determine if the values obtained converge on a result. Future investigations to obtain a better-constrained estimate of the biological carbon export in this region by measuring Nitrogen and Carbon uptake rates in the euphotic zone using dual, stable isotope tracer 15N/13C incubations in addition to the oxygen mass balance will be discussed.

Giesbrecht, K. E.; Hamme, R. C.

2008-12-01

359

Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B  

PubMed Central

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufacturing process. Therefore, we used a crossflow diafiltration system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work was to produce AFCo1 on pilot scale, while conserving the adjuvant properties. The proteoliposomes (raw material) were resuspended in a buffer containing sodium deoxycholate and were transformed into AFCo1 under the action of a calcium forming buffer. The detergent was removed from the protein solution by diafiltration to a constant volume. In this CFS, we used a hollow fiber cartridge from Amicon (polysulfona cartridge of 10 kDa porosity, 1mm channel diameter of fiber and 0.45 m2 area of filtration), allowing production of a batch of up to 20 L. AFCo1 were successfully produced by tangential filtration to pilot scale. The batch passed preliminary stability tests. Nasal immunization of BALB/c mice, induced specific saliva IgA and serum IgG. The induction of Th1 responses were demonstrated by the induction of IgG2a, IFN? and not IL-5. The adjuvant action over Neisseria (self) antigens and with co-administered (heterologous) antigens such as ovalbumin and a synthetic peptide from haemolytic Streptococcus B was also demonstrated.

2013-01-01

360

Multiple large foreign protein expression by a single recombinant baculovirus: a system for production of multivalent vaccines.  

PubMed

Baculovirus expression system offers the advantage of expression of several large proteins simultaneously by a single recombinant virus. To date, expression of multiple large (>100kDa) proteins has been hampered by the need to generate large constructs and repeat use of homologous sequence and promoter. The development of multi-loci baculovirus expression system overcomes these issues by enabling the recombination of large foreign sequences into different regions of the genome. In this paper, we have examined the co-expression of African horse sickness virus (AHSV) VP2 proteins from multiple serotypes in a single recombinant baculovirus. To this end, recombinant baculoviruses expressing multiple AHSV VP2 proteins were generated and it was found that up to six different AHSV serotypes (serotype 1, 3, 4, 5, 7 and 8) VP2 proteins (?120kDa) could be expressed simultaneously from different loci of baculovirus genome. The expression of VP2 of one serotype was not significantly hindered by the presence of other serotypes, although there were slight differences in expression level between different serotypes. The expression of VP2 of further serotypes from additional loci resulted in a lesser expression level of VP2 proteins. Based on these findings, three additional recombinant baculoviruses encompassing all nine AHSV serotypes were constructed (serotypes 1, 7, 8 or serotypes 2, 4, 5 or serotypes 3, 6, 9) and each of the triple recombinant viruses exhibited similar expression level of each VP2. This system allows for the expression of a number of large proteins that has the potential to be exploited for multivalent vaccines production. PMID:23872366

Kanai, Yuta; Athmaram, T N; Stewart, Meredith; Roy, Polly

2013-09-01

361

Vaccines for bluetongue.  

PubMed

Isolation of 8 serotypes of bluetongue virus (BTV) in Australia has led to widespread debate on how to prepare for an outbreak of bluetongue disease and the type of vaccine best suited to control bluetongue in Australia. This article describes the vaccine options under consideration by research workers and animal health administrators. The most widely discussed options are live attenuated virus, killed virus and virus-like particles (VLP) generated by recombinant baculoviruses. Attenuated virus vaccines are cheap and easy to produce and are administered in a single dose. They replicate in sheep without causing significant clinical effects and provide protection against challenge with virulent virus of the same serotype. The possibility that insects could acquire vaccine virus by feeding on vaccinated animals and transmit it to sheep or cattle cannot be eliminated. This poses a risk because attenuated viruses are teratogenic if ewes are infected in the first half of pregnancy. In addition, vaccine virus replication in insects and ruminants may lead to a reversion to virulence. Killed virus vaccines have been shown to be efficacious in small laboratory trials and cannot be transmitted to other animals in the field, but are significantly more expensive to produce than attenuated viruses and require at least 2 doses with adjuvant to elicit an immune response. More work is needed to properly assess their effectiveness and determine their cost of production. Recombinant VLP contain the 4 major structural proteins of BTV but no nucleic acid. VLP are relatively easy to isolate, but it is unlikely that the purification methods currently used in laboratories will be adapted for use commercially. Despite the enthusiasm of recent years, little commercial progress appears to have been made. Although scientific research in Australia and overseas has provided a number of options for development of bluetongue vaccines, the decisions on which to use in an outbreak are complex and will require, not only consideration of factors discussed here, but also agreement from industry and government. PMID:8893989

Murray, P K; Eaton, B T

1996-06-01

362

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

PubMed

Brazil, the Russian Federation, India, China and South Africa - the countries known as BRICS - have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018

Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah

2014-06-01

363

Impact of BRICS' investment in vaccine development on the global vaccine market  

PubMed Central

Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.

Milstien, Julie; Schmitt, Sarah

2014-01-01

364

Vaccines for seasonal and pandemic influenza.  

PubMed

Seasonal influenza continues to have a huge annual impact in the United States, accounting for tens of millions of illnesses, hundreds of thousands of excess hospitalizations, and tens of thousands of excess deaths. Vaccination remains the mainstay for the prevention of influenza. In the United States, 2 types of influenza vaccine are currently licensed: trivalent inactivated influenza vaccine and live attenuated influenza vaccine. Both are safe and effective in the populations for which they are approved for use. Children, adults <65 years of age, and the elderly all receive substantial health benefits from vaccination. In addition, vaccination appears to be cost-effective, if not cost saving, across the age spectrum. Despite long-standing recommendations for the routine vaccination of persons in high-priority groups, US vaccination rates remain too low across all age groups. Important issues to be addressed include improving vaccine delivery to current and expanded target groups, ensuring timely availability of adequate vaccine supply, and development of even more effective vaccines. Development of a vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. The use of existing technologies for influenza vaccine production would be the most straightforward approach, because these technologies are commercially available and licensing would be relatively simple. Approaches currently being tested include subvirion inactivated vaccines and cold-adapted, live attenuated vaccines. Preliminary results have suggested that, for some pandemic antigens, particularly H5, subvirion inactivated vaccines are poorly immunogenic, for reasons that are not clear. Data from evaluation of live pandemic vaccines are pending. Second-generation approaches designed to provide improved immune responses at lower doses have focused on adjuvants such as alum and MF59, which are currently licensed for influenza or other vaccines. Additional experimental approaches are required to achieve the ultimate goal for seasonal and pandemic influenza prevention--namely, the ability to generate broadly cross-reactive and durable protection in humans. PMID:17163383

Nichol, Kristin L; Treanor, John J

2006-11-01

365

Stockpile levels for pediatric vaccines: How much is enough?  

Microsoft Academic Search

In recent years, several factors have led to pediatric vaccine manufacturers experiencing vaccine production interruptions that resulted in vaccine supply shortages. One unfortunate consequence of such events is that not all children in the United States could be vaccinated on time, as set forth by the Recommended Childhood Immunization Schedule, and hence, created the potential for epidemic outbreaks of several

Sheldon H. Jacobson; Edward C. Sewell; Ruben A. Proano; Janet A. Jokela

2006-01-01

366

Therapeutic vaccination to treat chronic infectious diseases  

PubMed Central

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

Boukhebza, Houda; Bellon, Nadine; Limacher, Jean Marc; Inchauspe, Genevieve

2012-01-01

367

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

PubMed

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

Espeseth, David A; Lasher, Hiram

2010-12-01

368

Studies on the development of a medium with peptone and casein hydrolysate for the production of foot-and-mouth disease vaccine in BHK-21 cells.  

PubMed

Studies were undertaken to develop a cheaper medium with indigenous sources of peptone and casein hydrolysate for continuous culture of BHK-21 (suspension) cells and production of foot-and-mouth disease (FMD) vaccine. Eleven batches of experimental media were prepared using different indigenous sources of casein hydrolysate and peptone. These batches of media were tested for the growth of Razi BHK-21 cells in suspension and compared with the growth in control Eagle's medium. Out of eleven batches only four batches of the media produced cell growth equivalent to that with the Eagle's medium. Cells passaged in these batches of the experimental media supported virus growth and titres were comparable with those in Eagle's medium. Experimental batches of vaccine against FMD virus type A5 were prepared on a pilot scale as well as on a fermenter scale. The protection indices of these vaccine in guinea-pigs were satisfactory and induced 100% protection in cattle. One source each of peptone and casein hydrolysate was found suitable for the experimental medium. The medium developed is able to replace 10 out of 13 amino acids and also tryptose phosphate broth in Eagle's medium and is expected to reduce the cost of medium by 33% compared with Eagle's medium. PMID:2554603

Saha, S N; Sen, A K

1989-08-01

369

A synthetic biology approach to self-regulatory recombinant protein production in Escherichia coli  

PubMed Central

Background Recombinant protein production is a process of great industrial interest, with products that range from pharmaceuticals to biofuels. Since high level production of recombinant protein imposes significant stress in the host organism, several methods have been developed over the years to optimize protein production. So far, these trial-and-error techniques have proved laborious and sensitive to process parameters, while there has been no attempt to address the problem by applying Synthetic Biology principles and methods, such as integration of standardized parts in novel synthetic circuits. Results We present a novel self-regulatory protein production system that couples the control of recombinant protein production with a stress-induced, negative feedback mechanism. The synthetic circuit allows the down-regulation of recombinant protein expression through a stress-induced promoter. We used E. coli as the host organism, since it is widely used in recombinant processes. Our results show that the introduction of the self-regulatory circuit increases the soluble/insoluble ratio of recombinant protein at the expense of total protein yield. To further elucidate the dynamics of the system, we developed a computational model that is in agreement with the observed experimental data, and provides insight on the interplay between protein solubility and yield. Conclusion Our work introduces the idea of a self-regulatory circuit for recombinant protein products, and paves the way for processes with reduced external control or monitoring needs. It demonstrates that the library of standard biological parts serves as a valuable resource for initial synthetic blocks that needs to be further refined to be successfully applied in practical problems of biotechnological significance. Finally, the development of a predictive model in conjunction with experimental validation facilitates a better understanding of the underlying dynamics and can be used as a guide to experimental design.

2012-01-01

370

Fate of phosphorus from biological aerobic treatment of pig slurry. By-products characterization and recovery.  

PubMed

The fate of phosphorus distribution in the products obtained from biological aerobic treatment of pig slurry, e.g. separated solids, liquid effluent and sludge, was monitored in three different farm-scale units. Samples of raw slurry, solid products, aerated slurry, liquid effluent and sludge were characterised and analysed for their concentration in total phosphorus, nitrogen content and heavy metals (Cu and Zn). At each treatment stage, nitrogen, phosphorus and heavy metals mass balance between input and output was established. Moreover, liquid products were characterised and analysed both for their total and dissolved ortho-phosphate content. Separated solids, sludge and liquid effluent represented 5%, 15-40% and 75-83% of the mass of the raw slurry, respectively. A mechanical separation step prior to aeration allowed the export of 25-30% of total phosphorus for further use as organic fertiliser. A large amount of total phosphorus (e.g. 60-70%) was located in sludge while phosphorus remaining in liquid effluent was about 15-25%. Raw slurry separation and sufficient aeration allowed phosphorus to concentrate in the sludge. Insufficient aeration resulted in the release of phosphorus as dissolved ortho-phosphate within the liquid effluent. Finally, relevance of the agronomic use of the products was discussed and improvements of biological aerobic treatment to enhance phosphorus removal and/or recovery were considered. PMID:14733385

Daumer, M L; Beline, F; Guiziou, F

2003-11-01

371

Biological pretreatment of rubberwood with Ceriporiopsis subvermispora for enzymatic hydrolysis and bioethanol production.  

PubMed

Rubberwood (Hevea brasiliensis), a potential raw material for bioethanol production due to its high cellulose content, was used as a novel feedstock for enzymatic hydrolysis and bioethanol production using biological pretreatment. To improve ethanol production, rubberwood was pretreated with white rot fungus Ceriporiopsis subvermispora to increase fermentation efficiency. The effects of particle size of rubberwood (1 mm, 0.5 mm, and 0.25 mm) and pretreatment time on the biological pretreatment were first determined by chemical analysis and X-ray diffraction and their best condition obtained with 1 mm particle size and 90 days pretreatment. Further morphological study on rubberwood with 1 mm particle size pretreated by fungus was performed by FT-IR spectra analysis and SEM observation and the result indicated the ability of this fungus for pretreatment. A study on enzymatic hydrolysis resulted in an increased sugar yield of 27.67% as compared with untreated rubberwood (2.88%). The maximum ethanol concentration and yield were 17.9 g/L and 53% yield, respectively, after 120 hours. The results obtained demonstrate that rubberwood pretreated by C. subvermispora can be used as an alternative material for the enzymatic hydrolysis and bioethanol production. PMID:24167813

Nazarpour, Forough; Abdullah, Dzulkefly Kuang; Abdullah, Norhafizah; Motedayen, Nazila; Zamiri, Reza

2013-01-01

372

Laser-initiated decomposition products of indocyanine green (ICG) and carbon black sensitized biological tissues  

NASA Astrophysics Data System (ADS)

Organic dyes have found increasing use a s sensitizers in laser surgical procedures, due to their high optical absorbances. Little is known, however, about the nature of the degradation products formed when these dyes are irradiated with a laser. Previous work in our laboratories has shown that irradiation of polymeric and biological tissues with CO2 and Nd:YAG lasers produces a host of volatile and semivolatile by-products, some of which are known to be potential carcinogens. This work focuses on the identification of the chemical by-products formed by diode laser and Nd:YAG laser irradiation of indocyanine green (ICG) and carbon black based ink sensitized tissues, including bone, tendon and sheep's teeth. Samples were mounted in a 0.5-L Pyrex sample chamber equipped with quartz optical windows, charcoal filtered air inlet and an outlet attached to an appropriate sample trap and a constant flow pump. By-products were analyzed by GC/MS and HPLC. Volatiles identified included benzene and formaldehyde. Semi-volatiles included traces of polycyclic aromatics, arising from the biological matrix and inks, as well as fragments of ICG and the carbon ink components. The significance of these results will be discussed, including the necessity of using appropriate evacuation devices when utilizing lasers for surgical procedures.

Kokosa, John M.; Przyjazny, Andrzej; Bartels, Kenneth E.; Motamedi, Massoud; Hayes, Donald J.; Wallace, David B.; Frederickson, Christopher J.

1997-05-01

373

Biological Pretreatment of Rubberwood with Ceriporiopsis subvermispora for Enzymatic Hydrolysis and Bioethanol Production  

PubMed Central

Rubberwood (Hevea brasiliensis), a potential raw material for bioethanol production due to its high cellulose content, was used as a novel feedstock for enzymatic hydrolysis and bioethanol production using biological pretreatment. To improve ethanol production, rubberwood was pretreated with white rot fungus Ceriporiopsis subvermispora to increase fermentation efficiency. The effects of particle size of rubberwood (1?mm, 0.5?mm, and 0.25?mm) and pretreatment time on the biological pretreatment were first determined by chemical analysis and X-ray diffraction and their best condition obtained with 1?mm particle size and 90 days pretreatment. Further morphological study on rubberwood with 1 mm particle size pretreated by fungus was performed by FT-IR spectra analysis and SEM observation and the result indicated the ability of this fungus for pretreatment. A study on enzymatic hydrolysis resulted in an increased sugar yield of 27.67% as compared with untreated rubberwood (2.88%). The maximum ethanol concentration and yield were 17.9?g/L and 53% yield, respectively, after 120 hours. The results obtained demonstrate that rubberwood pretreated by C. subvermispora can be used as an alternative material for the enzymatic hydrolysis and bioethanol production.

Nazarpour, Forough; Abdullah, Dzulkefly Kuang; Abdullah, Norhafizah; Motedayen, Nazila; Zamiri, Reza

2013-01-01

374

Vaccines and infectious disease  

Microsoft Academic Search

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

Mark A. Fletcher; Pierre Saliou

375

Molecular identification of the vaccine strain from the inactivated oil emulsion H9N2 low pathogenic avian influenza vaccine  

PubMed Central

In order to control the H9N2 subtype low pathogenic avian influenza (LPAI), an inactivated vaccine has been used in Korea since 2007. The Korean veterinary authority permitted the use of a single H9N2 LPAI vaccine strain to simplify the evolution of the circulating virus due to the immune pressure caused by the vaccine use. It is therefore important to determine the suitability of the vaccine strain in the final inactivated oil emulsion LPAI vaccine. In this study, we applied molecular rather than biological methods to verify the suitability of the vaccine strain used in commercial vaccines and successfully identified the strain by comparing the nucleotide sequences of the hemagglutinin and neuraminidase genes with that of the permitted Korean LPAI vaccine strain. It is thought that the method used in this study might be successfully applied to other viral genes of the LPAI vaccine strain and perhaps to other veterinary oil emulsion vaccines.

Choi, Jun-Gu; Kim, Ji-Yeon; Kim, Yeon-Hee; Paek, Mi-Ra; Yang, Dong-Kun; Son, Seong-Wan; Kim, Jae-Hong

2010-01-01

376

India's vaccine inventor: Gursaran Talwar.  

PubMed

Dr Gursaran Talwar, 68, has worked for almost 20 years to find a safe, long-lasting, and reversible contraceptive vaccine. The Director of India's National Institute of Immunology began his research in the mid 1970s with financial support from the Indian government and IDRC. Toxicology studies were conducted for 10 years. The vaccine increases production of antibodies against human chorionic gonadotropin (HCG), a hormone which assists in preparing the uterus for embryo implantation. The vaccine blocks this process and prevents pregnancy. Without the vaccine, 50-75% of embryos fail to be implanted because of antibodies to HCG; with the vaccine, 100% do. The vaccine is administered once a month for 3 months. Although another form of contraception must be used during this time, protection afterwards lasts for a year. Boosters are given annually. In a clinical study of 88 vaccinated women, 1 pregnancy occurred in 821 menstrual cycles. Fertility returns with discontinuation of the vaccinations. Dr Talwar is also working on a contraceptive for the 3-month period using the purified extract of the neem tree, a male contraceptive, a treatment for prostate cancer, and a vaccine against leprosy. PMID:12288547

Rai, U

1995-01-01

377

Detection of Avian Retroviruses in Vaccines by Amplification on DF-1 Cells with Immunostaining and Fluorescent Product-Enhanced Reverse Transcriptase Endpoint Methods  

PubMed Central

In order to ensure the safety of vaccines produced on avian cells, rigorous testing for the absence of avian retroviruses must be performed. Current methods used to detect avian retroviruses often exhibit a high invalid-test/false-positive rate, rely on hard-to-secure reagents, and/or have readouts that are difficult to standardize. Herein, we describe the development and validation of two consistent and sensitive methods for the detection of avian retroviruses in vaccines: viral amplification on DF-1 cells followed by immunostaining for the detection of avian leukosis virus (ALV) and viral amplification on DF-1 cells followed by fluorescent product-enhanced reverse transcriptase (F-PERT) for the detection of all avian retroviruses. Both assays share an infectivity stage on DF-1 cells followed by a different endpoint readout depending on the retrovirus to be detected. Validation studies demonstrated a limit of detection of one 50% cell culture infectious dose (CCID50)/ml for retrovirus in a 30-ml test inoculum volume for both methods, which was as sensitive as a classical method used in the vaccine industry, namely, viral amplification on primary chicken embryo fibroblasts followed by the complement fixation test for avian leukosis virus (COFAL). Furthermore, viral amplification on DF-1 cells followed by either immunostaining or F-PERT demonstrated a sensitivity that exceeds the regulatory requirements for detection of ALV strains. A head-to-head comparison of the two endpoint methods showed that viral amplification on DF-1 cells followed by F-PERT is a suitable method to be used as a stand-alone test to ensure that vaccine preparations are free from infectious avian retroviruses.

Dupont, Dominique; Riou, Patrice; Armanet, Corinne; Edamura, Kerrie Nichol; Martinho, Briolange; Serres, Aurelie; Jacouton, Severine; Detrez, Valerie; McNeil, Bryan; Schreiber, Martha; Gaillac, David; Bonnevay, Thierry; Gisonni-Lex, Lucy; Mallet, Laurent

2013-01-01

378

Mass and energy balance constraints on the biological production of chemicals from coal  

SciTech Connect

Several organic chemicals, including methane and ethanol, may be produced by the bioprocessing of coal. This may be done either by direct microbial attack on the coal, or indirectly by the bioprocessing of solubilized coal. As in chemical liquefaction and gasification, the relative amounts of the various products that can be produced are severely constrained by mass and energy balance considerations. The main differences in biological processing are that water is a ubiquitous reactant, carbon dioxide a common product, and that some of the carbon and nitrogen in the coal may go to the synthesis of new biomass rather than products. The conventional biotechnological yield analysis applied to coal processing has several interesting consequences. The mass balance reduces to a balance of available electrons, and coal has a similar oxidation/reduction state to both carbohydrates and biomass. This makes high product yields feasible particularly under anaerobic conditions, although leaving open the question of whether the relevant hydrolase enzymes exist. Recommendations are made on products, and combinations of two products, that may be made with high yields and economic return. The energy balance provides little extra information. A general intracellular energy balance can be written in terms of the production and consumption of ATP, but much of the necessary information on the metabolic pathways is currently not available for coal processing microorganisms. 9 refs., 2 figs., 2 tabs.

Andrews, G.

1990-01-01

379

Method for assessing the impact of emission gasses on physiology and productivity in biological methanogenesis.  

PubMed

This contribution presents a method for quantification of the impact of emission gasses on the methane production with hydrogenotrophic methanogenic archaea. The developed method allows a robust quantification of the influence of real gasses on the volumetric productivity of methanogenic cultures by uncoupling physiological and mass transfer effects. This is achieved over reference experiments with pure H2 and CO2, simulating the mass transfer influence of the non-convertible side components by addition of N2 to the reactant stream. Furthermore, this method was used to examine the performance of Methanothermobacter marburgensis on different emission gasses. None of the present side components had a negative effect on the volumetric methane production rate. The presented method showed to be ready to use as a generic tool for feasibility studies and quantification of the physiological impact regarding the use of exhaust gasses as reactant gas for the biological methanogenesis. PMID:23582218

Seifert, A H; Rittmann, S; Bernacchi, S; Herwig, C

2013-05-01

380

HLA haplotype and supertype associations with cellular immune responses and cytokine production in healthy children after rubella vaccine  

Microsoft Academic Search

Secreted rubella virus-specific cytokines reflect the immunologic mechanisms underlying adoptive immune responses and are significant markers of immunity to rubella. We studied the association between measures of cellular (cytokine and frequency of cytokine-secreted cells) immune responses and HLA haplotypes (with frequencies of ?1%) and supertypes among 738 healthy children following two doses of rubella vaccine. Haplotype effects were estimated while

Inna G. Ovsyannikova; Robert A. Vierkant; V. Shane Pankratz; Megan M. O’Byrne; Robert M. Jacobson; Gregory A. Poland

2009-01-01

381

Vaccination for Invasive Canine Meningioma Induces in Situ Production of Antibodies Capable of Antibody-Dependent Cell-Mediated Cytotoxicity  

PubMed Central

Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. Interferon gamma elaborating T cells were detected in the peripheral blood of two cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and heat shock protein 60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, demonstrating common antigens across breed and species. Histological analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in post-treatment compared to pre-treatment samples. Tumor-reactive antibodies were capable of inducing antibody dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data demonstrate the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development towards human trials.

Andersen, Brian M.; Pluhar, G. Elizabeth; Seiler, Charles E.; Goulart, Michelle R.; SantaCruz, Karen S.; Schutten, Melissa M.; Meints, Joyce P.; O'Sullivan, M. Gerard; Bentley, R. Timothy; Packer, Rebecca A.; Thomovsky, Stephanie A.; Chen, Annie V.; Faissler, Dominik; Hunt, Matthew A.; Ohlfest, John R.

2013-01-01

382

Epidemiological determinants of successful vaccine development.  

PubMed

Epidemiological determinants of successful vaccine development were explored using measurable biological variables including antigenic stability and requirement of T-cell immunity. Employing a logistic regression model, we demonstrate that a high affinity with blood and immune cells and pathogen interactions (e.g. interference) would be the risk factors of failure for vaccine development. PMID:23471119

Nishiura, Hiroshi; Mizumoto, Kenji

2013-01-01

383

[Measles vaccination].  

PubMed

France is facing since 2008 a re-emerging measles outbreak affecting a high proportion of adults currently not or not correctly vaccinated. The non application since 30 years of the immunization program on measles mumps and rubella is the cause of this situation, despite the efficacy and the good tolerance of this vaccine has been demonstrated. The present epidemic is expected to go on, as long as the millions of measles susceptible people have not been either affected or vaccinated. A 95% protection rate is needed to interrupt the circulation of the virus. So, the objective of the French Plan for elimination of measles and congenital rubella is to reach at least a 95% vaccination coverage for the first dose and 80% for the second dose. The immunization recommendations should be strictly respected: first dose of MMR vaccine at 12 months and second dose within the second year of life. In this context, catch up immunization of children, adolescents and young adults (up to 30 year) not or not correctly vaccinated is particularly important, as well as the post exposure prophylactic measures, including vaccination. PMID:21425529

Floret, Daniel

2010-12-20

384

Molar-Based Targeted Metabolic Profiling of Cyanobacterial Strains with Potential for Biological Production  

PubMed Central

Recently, cyanobacteria have become one of the most attractive hosts for biochemical production due to its high proliferative ability and ease of genetic manipulation. Several researches aimed at biological production using modified cyanobacteria have been reported previously. However, to improve the yield of bioproducts, a thorough understanding of the intercellular metabolism of cyanobacteria is necessary. Metabolic profiling techniques have proven to be powerful tools for monitoring cellular metabolism of various organisms and can be applied to elucidate the details of cyanobacterial metabolism. In this study, we constructed a metabolic profiling method for cyanobacteria using 13C-labeled cell extracts as internal standards. Using this method, absolute concentrations of 84 metabolites were successfully determined in three cyanobacterial strains which are commonly used as background strains for metabolic engineering. By comparing the differences in basic metabolic potentials of the three cyanobacterial strains, we found a well-correlated relationship between intracellular energy state and growth in cyanobacteria. By integrating our results with the previously reported biological production pathways in cyanobacteria, we found putative limiting step of carbon flux. The information obtained from this study will not only help gain insights in cyanobacterial physiology but also serve as a foundation for future metabolic engineering studies using cyanobacteria.

Dempo, Yudai; Ohta, Erika; Nakayama, Yasumune; Bamba, Takeshi; Fukusaki, Eiichiro

2014-01-01

385

Molar-based targeted metabolic profiling of cyanobacterial strains with potential for biological production.  

PubMed

Recently, cyanobacteria have become one of the most attractive hosts for biochemical production due to its high proliferative ability and ease of genetic manipulation. Several researches aimed at biological production using modified cyanobacteria have been reported previously. However, to improve the yield of bioproducts, a thorough understanding of the intercellular metabolism of cyanobacteria is necessary. Metabolic profiling techniques have proven to be powerful tools for monitoring cellular metabolism of various organisms and can be applied to elucidate the details of cyanobacterial metabolism. In this study, we constructed a metabolic profiling method for cyanobacteria using 13C-labeled cell extracts as internal standards. Using this method, absolute concentrations of 84 metabolites were successfully determined in three cyanobacterial strains which are commonly used as background strains for metabolic engineering. By comparing the differences in basic metabolic potentials of the three cyanobacterial strains, we found a well-correlated relationship between intracellular energy state and growth in cyanobacteria. By integrating our results with the previously reported biological production pathways in cyanobacteria, we found putative limiting step of carbon flux. The information obtained from this study will not only help gain insights in cyanobacterial physiology but also serve as a foundation for future metabolic engineering studies using cyanobacteria. PMID:24957038

Dempo, Yudai; Ohta, Erika; Nakayama, Yasumune; Bamba, Takeshi; Fukusaki, Eiichiro

2014-01-01

386

Characterization of Endogenous Avian Leukosis Viruses in Chicken Embryonic Fibroblast Substrates Used in Production of Measles and Mumps Vaccines  

PubMed Central

Previous findings of low levels of reverse transcriptase (RT) activity in chick cell-derived measles and mumps vaccines showed this activity to be associated with virus particles containing RNA of both subgroup E endogenous avian leukosis viruses (ALV-E) and endogenous avian viruses (EAV). These particles originate from chicken embryonic fibroblast (CEF) substrates used for propagating vaccine strains. To better characterize vaccine-associated ALV-E, we examined the endogenous ALV proviruses (ev loci) present in a White Leghorn CEF substrate pool by restriction fragment length polymorphism. Five ev loci were detected, ev-1, ev-3, ev-6, ev-18, andev-19. Both ev-18 and ev-19 can express infectious ALV-E, while ev-1, ev-3, and ev-6 are defective. We analyzed the full-length sequence of ev-1 and identified an adenosine insertion within the pol RT-? region at position 5026, which results in a truncated RT-? and integrase. We defined the 1,692-bp deletion in the gag-pol region of ev-3, and we found that in ev-6, sequences from the 5? long terminal repeat to the 5? pol region were absent. Based on the sequences of the ev loci, RT-PCR assays were developed to examine expression of ALV-E particles (EV) in CEF supernatants. Both ev-1- and ev-3-like RNA sequences were identified, as well as two other RNA sequences with intact pol regions, presumably of ev-18 and ev-19 origin. Inoculation of susceptible quail fibroblasts with CEF culture supernatants from both 5-azacytidine-induced and noninduced CEF led to ALV infection, confirming the presence of infectious ALV-E. Our data demonstrate that both defective and nondefective ev loci can be present in CEF vaccine substrates and suggest that both ev classes may contribute to the ALV present in vaccines.

Johnson, Jeffrey A.; Heneine, Walid

2001-01-01

387

21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...  

Code of Federal Regulations, 2011 CFR

...Stockpile. (b)(1)(i) A Strategic National Stockpile official or any entity that manufactures (including labeling, packing, relabeling, or repackaging), distributes, or stores a biological product that is or will be included in the...

2011-04-01

388

Risk in Vaccine Research and Development Quantified  

PubMed Central

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

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

2013-01-01

389

Inactivated Francisella tularensis Live Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion  

Microsoft Academic Search

Francisella tularensis is a gram-negative intracellular bacterium that is considered to be a potential category A biological weapon due to its extreme virulence. Although vaccination with the attenuated live vaccine strain (LVS) of F. tularensis can protect against lethal challenge, use of inactivated or subunit forms as vaccine candidates for induction of protective antibody responses has not been fully evaluated.

Shawn D. Baron; Rajendra Singh; Dennis W. Metzger

2007-01-01

390

Macrofaunal production and biological traits: Spatial relationships along the UK continental shelf  

NASA Astrophysics Data System (ADS)

Biological trait analysis (BTA) is increasingly being employed to improve our understanding of the ecological functioning of marine benthic invertebrate communities. However, changes in trait composition are seldomly compared with concomitant changes in metrics of ecological function. Consequently, inferences regarding the functional implications of any changes are often anecdotal; we currently have a limited understanding of the functional significance of the traits commonly used. In this study, we quantify the relationship between benthic invertebrate trait composition and secondary production estimates using data spanning almost the breadth of the UK continental shelf.

Bolam, S. G.; Eggleton, J. D.

2014-04-01

391

Stockpile levels for pediatric vaccines: how much is enough?  

PubMed

In recent years, several factors have led to pediatric vaccine manufacturers experiencing vaccine production interruptions that resulted in vaccine supply shortages. One unfortunate consequence of such events is that not all children in the United States could be vaccinated on time, as set forth by the Recommended Childhood Immunization Schedule, and hence, created the potential for epidemic outbreaks of several childhood diseases. The Centers for Disease Control and Prevention (CDC) have responded to such events by releasing vaccine supplies from the national pediatric vaccine stockpiles, which were designed to mitigate the impact of vaccine production interruptions. This paper analyzes the CDC-proposed vaccine stockpile levels using a stochastic inventory model. The results from this analysis examine the adequacy of the proposed pediatric vaccine stockpile levels, as well as provide insights into what the appropriate pediatric vaccine stockpile levels should be to achieve prespecified vaccination coverage rates. Given that the average pediatric vaccine production interruption has lasted more than 1 year, the model is used to compute appropriate pediatric vaccine stockpile levels sufficient to absorb the effect of such vaccine production interruptions. The level of funding needed to create such pediatric vaccine stockpile levels is also reported. PMID:16522344

Jacobson, Sheldon H; Sewell, Edward C; Proano, Ruben A; Jokela, Janet A

2006-04-24

392

Investigations of porcine circovirus type 1 (PCV1) in vaccine-related and other cell lines.  

PubMed

Porcine circovirus type 1 (PCV1) is highly prevalent in swine and was recently reported in some rotavirus vaccines. Since animal-derived raw materials, such as cells, trypsin, and serum, can be a major source of introducing virus contamination in biological products, we have investigated PCV1 in several cell lines obtained from ATCC that have broad use in research, diagnostics, or vaccine development. It is expected that these cell lines have been exposed to bovine and porcine viruses during their establishment and passage history due to the use of serum and trypsin that was not qualified according to current testing guidances or processed using new virus-inactivation methods. This study showed that Vero, MRC-5, and CEFs, which represent cell substrates used in some U.S. licensed vaccines, and other cell lines used in investigational vaccines, such as MDCK, HEK-293, HeLa, and A549, were negative for PCV1 using a nested PCR assay; some were also confirmed negative by infectivity analysis. However, MDBK cells, which are used for some animal vaccines, contained PCV1 sequences, although no virus was isolated. Although the results showed that PCV infection may not have occurred under previous culture conditions, the recent cases of vaccine contamination emphasizes the need for continued efforts to reduce the likelihood of introducing viruses from animal-derived materials used in product manufacture. PMID:21835219

Ma, Hailun; Shaheduzzaman, Syed; Willliams, Dhanya K; Gao, Yamei; Khan, Arifa S

2011-10-26

393

Biological Air Emissions Control for an Energy Efficient Forest Products Industry of the Future  

SciTech Connect

The U.S. wood products industry is a leader in the production of innovative wood materials. New products are taking shape within a growth industry for fiberboard, plywood, particle board, and other natural material-based energy efficient building materials. However, at the same time, standards for clean air are becoming ever stricter. Emissions of volatile organic compounds (VOCs) and hazardous air pollutants (HAPs) during production of wood products (including methanol, formaldehyde, acetylaldehyde, and mercaptans) must be tightly controlled. Conventional VOC and HAP emission control techniques such as regenerative thermal oxidation (RTO) and regenerative catalytic oxidation (RCO) require significant amounts of energy and generate secondary pollutants such as nitrogen oxides and spent carbon. Biological treatment of air emissions offers a cost-effective and sustainable control technology for industrial facilities facing increasingly stringent air emission standards. A novel biological treatment system that integrates two types of biofilter systems, promises significant energy and cost savings. This novel system uses microorganisms to degrade air toxins without the use of natural gas as fuel or the creation of secondary pollutants. The replacement of conventional thermal oxidizers with biofilters will yield natural gas savings alone in the range of $82,500 to $231,000 per year per unit. Widespread use of biofilters across the entire forest products industry could yield fuel savings up to 5.6 trillion Btu (British thermal units) per year and electricity savings of 2.1 trillion Btu per year. Biological treatment systems can also eliminate the production of NOx, SO2, and CO, and greatly reduce CO2 emissions, when compared to conventional thermal oxidizers. Use of biofilters for VOC and HAP emission control will provide not only the wood products industry but also the pulp and paper industry with a means to cost-effectively control air emissions. The goal of this project was to demonstrate a novel sequential treatment technology that integrates two types of biofilter systems – biotrickling filtration and biofiltration – for controlling forest product facility air emissions with a water-recycling feature for water conservation. This coupling design maximizes the conditions for microbial degradation of odor causing compounds at specific locations. Water entering the biotrickling filter is collected in a sump, treated, and recycled back to the biotrickling filter. The biofilter serves as a polishing step to remove more complex organic compounds (i.e., terpenes). The gaseous emissions from the hardboard mill presses at lumber plants such as that of the Stimson Lumber Company contain both volatile and condensable organic compounds (VOC and COC, respectively), as well as fine wood and other very small particulate material. In applying bio-oxidation technology to these emissions Texas A&M University-Kingsville (TAMUK) and Bio•Reaction (BRI) evaluated the potential of this equipment to resolve two (2) control issues which are critical to the industry: • First, the hazardous air pollutant (HAP) emissions (primarily methanol and formaldehyde) and • Second, the fine particulate and COC from the press exhaust which contribute to visual emissions (opacity) from the stack. In a field test in 2006, the biological treatment technology met the HAP and COC control project objectives and demonstrated significantly lower energy use (than regenerative thermal oxidizers (RTOs) or regenerative catalytic oxidizers (RCOs), lower water use (than conventional scrubbers) all the while being less costly than either for maintenance. The project was successfully continued into 2007-2008 to assist the commercial partner in reducing unit size and footprint and cost, through added optimization of water recycle and improved biofilm activity, and demonstration of opacity removal capabilities.

Jones, K; Boswell, J.

2009-05-28

394

Intracellular delivery of a protein antigen with an endosomal-releasing polymer enhances CD8 T-cell production and prophylactic vaccine efficacy.  

PubMed

Protein-based vaccines have significant potential as infectious disease and anticancer therapeutics, but clinical impact has been limited in some applications by their inability to generate a coordinated cellular immune response. Here, a pH-responsive carrier incorporating poly(propylacrylic acid) (PPAA) was evaluated to test whether improved cytosolic delivery of a protein antigen could enhance CD8+ cytotoxic lymphocyte generation and prophylactic tumor vaccine responses. PPAA was directly conjugated to the model ovalbumin antigen via reducible disulfide linkages and was also tested in a particulate formulation after condensation with cationic poly(dimethylaminoethyl methacrylate) (PDMAEMA). Intracellular trafficking studies revealed that both PPAA-containing formulations were stably internalized and evaded exocytotic pathways, leading to increased intracellular accumulation and potential access to the cytosolic MHC-1 antigen presentation pathway. In an EG.7-OVA mouse tumor protection model, both PPAA-containing carriers robustly inhibited tumor growth and led to an approximately 3.5-fold increase in the longevity of tumor-free survival relative to controls. Mechanistically, this response was attributed to the 8-fold increase in production of ovalbumin-specific CD8+ T-lymphocytes and an 11-fold increase in production of antiovalbumin IgG. Significantly, this is one of the first demonstrated examples of in vivo immunotherapeutic efficacy using soluble protein-polymer conjugates. These results suggest that carriers enhancing cytosolic delivery of protein antigens could lead to more robust CD8+ T-cell response and demonstrate the potential of pH-responsive PPAA-based carriers for therapeutic vaccine applications. PMID:21043513

Foster, Suzanne; Duvall, Craig L; Crownover, Emily F; Hoffman, Allan S; Stayton, Patrick S

2010-12-15

395

Economics of vaccines revisited  

PubMed Central

Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct and indirect) to be measured in a population when using a cohort model;1 appropriate rules about discounting the long-term impact of vaccines are absent jeopardizing therefore their value at the initial investment;2 the presence of opposite contexts when introducing the vaccine in developed vs. the developing world with high benefits, low initial health care investment for the latter vs. marginal benefit and high cost for the former; with a corresponding paradox for the vaccine becoming very cost-effective in low income countries but rather medium in middle low to high middle income countries;3 and the type of trial assessment for the newer vaccines is now often performed with immunogenicity reaction instead of clinical endpoints which still leaves questions on their real impact and their head-to-head comparison.4

Postma, Maarten J.; Standaert, Baudouin A.

2013-01-01

396

An integrated cell-free metabolic platform for protein production and synthetic biology  

PubMed Central

Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co-activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell-free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements.

Jewett, Michael C; Calhoun, Kara A; Voloshin, Alexei; Wuu, Jessica J; Swartz, James R

2008-01-01

397

Studies of Respiratory Syncytial Virus Vaccines.  

National Technical Information Service (NTIS)

Studies of Respiratory Syncytial virus vaccines included both biological and physical aspects with the principle objective being a study of the banding of RS virus in the density gradient ultracentrifuge. Various studies on virus propagation both in the B...

R. N. Hull C. B. Reimer L. F. Ellis

1966-01-01

398

78 FR 29698 - Availability of an Environmental Assessment for Field Testing a Canine Lymphoma Vaccine, DNA  

Federal Register 2010, 2011, 2012, 2013

...Field Testing a Canine Lymphoma Vaccine, DNA AGENCY: Animal and Plant Health Inspection...an unlicensed Canine Lymphoma Vaccine, DNA. The environmental assessment, which is...Inc. Product: Canine Lymphoma Vaccine, DNA. Possible Field Test Locations:...

2013-05-21

399

Traditional and New Influenza Vaccines  

PubMed Central

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

Wong, Sook-San

2013-01-01

400

Typhoid Vaccine  

MedlinePLUS

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

401

Typhoid Vaccine  

MedlinePLUS

... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, weakness, stomach ... a typhoid carrier. Laboratory workers who work with Salmonella Typhi bacteria. Inactivated Typhoid Vaccine (Shot)Should not ...

402

Pertussis Vaccine  

Cancer.gov

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

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