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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. PMID:22478749

ADAMS, KATHERINE T.

2009-01-01

2

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2011-03-14

3

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2011-07-22

4

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2013-04-05

5

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2012-01-25

6

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

Federal Register 2010, 2011, 2012, 2013, 2014

...FDA-2010-N-0001] Vaccines and Related Biological Products Advisory Committee; Notice...Name of Committee: Vaccines and Related Biological Products Advisory Committee. General...would constitute a clearly unwarranted invasion of personal privacy (5 U.S.C....

2010-08-06

7

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2011-09-07

8

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2011-08-23

9

Production, testing and perspectives of IPV and IPV combination vaccines: GSK biologicals' view  

Microsoft Academic Search

GSK Biologicals has been involved in the production of Polio vaccine since the early start of Polio vaccination, beginning with the first generation of Inactivated Polio Vaccine (IPV). Over time, the company has developed solid industrial experience and knowledge that significantly contributes today to the quality of our Polio vaccines.GSK Biologicals' current IPV is now routinely produced according to the

Michel Duchêne

2006-01-01

10

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

Federal Register 2010, 2011, 2012, 2013, 2014

...FDA-2012-N-0001] Vaccines and Related Biological Products...Committee: Vaccines and Related Biological Products...be webcast. The link for the webcast is...videocast.nih.gov. Contact Person: Donald W...committee meeting link. Procedure: Interested...may be made to the contact person on or...

2013-01-25

11

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

Federal Register 2010, 2011, 2012, 2013, 2014

...effectiveness of vaccinating males and females with Gardasil manufactured by Merck & Co. for the prevention of anal dysplasia and anal cancer. FDA intends to make background material available to the public no later than 2 business days before...

2010-09-28

12

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

Federal Register 2010, 2011, 2012, 2013, 2014

...committee will meet in open session to discuss and make recommendations on the safety and immunogenicity of an Influenza A (H5N1) Virus Monovalent Vaccine manufactured by GlaxoSmithKline. On November 15, 2012, the committee will meet in open...

2012-10-17

13

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

Federal Register 2010, 2011, 2012, 2013, 2014

...the morning, the committee will review and discuss available data regarding the unexpected finding of DNA originating from porcine circovirus type 1 (PCV 1) in Rotarix, a U.S. licensed vaccine manufactured by GlaxoSmithKline and indicated for the...

2010-04-08

14

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

Federal Register 2010, 2011, 2012, 2013, 2014

...and USSN 12/838,292, filed Jul 16, 2010; entitled ``Influenza DNA Vaccination and Methods of Use Thereof'', by Rao et al (NIAID/VRC) (E-050-2008/0,1,2,3), to Newport Laboratories having a place of business in 1520...

2011-12-21

15

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

16

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

17

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

NASA Astrophysics Data System (ADS)

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

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

2002-03-01

18

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

PubMed

Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries. PMID:25697690

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

2015-05-01

19

Immunogenomics and systems biology of vaccines  

PubMed Central

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

Buonaguro, Luigi; Pulendran, Bali

2011-01-01

20

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

Microsoft Academic Search

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

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

2008-01-01

21

Plants as bioreactors for the production of vaccine antigens.  

PubMed

Plants have been identified as promising expression systems for commercial production of vaccine antigens. In phase I clinical trials several plant-derived vaccine antigens have been found to be safe and induce sufficiently high immune response. Thus, transgenic plants, including edible plant parts are suggested as excellent alternatives for the production of vaccines and economic scale-up through cultivation. Improved understanding of plant molecular biology and consequent refinement in the genetic engineering techniques have led to designing approaches for high level expression of vaccine antigens in plants. During the last decade, several efficient plant-based expression systems have been examined and more than 100 recombinant proteins including plant-derived vaccine antigens have been expressed in different plant tissues. Estimates suggest that it may become possible to obtain antigen sufficient for vaccinating millions of individuals from one acre crop by expressing the antigen in seeds of an edible legume, like peanut or soybean. In the near future, a plethora of protein products, developed through 'naturalized bioreactors' may reach market. Efforts for further improvements in these technologies need to be directed mainly towards validation and applicability of plant-based standardized mucosal and edible vaccines, regulatory pharmacology, formulations and the development of commercially viable GLP protocols. This article reviews the current status of developments in the area of use of plants for the development of vaccine antigens. PMID:19356740

Tiwari, Siddharth; Verma, Praveen C; Singh, Pradhyumna K; Tuli, Rakesh

2009-01-01

22

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. PMID:21664680

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

2011-01-01

23

Production of glycoprotein vaccines in Escherichia coli  

Microsoft Academic Search

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

Julian Ihssen; Michael Kowarik; Sandro Dilettoso; Cyril Tanner; Michael Wacker; Linda Thöny-Meyer

2010-01-01

24

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

PubMed

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

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

2015-02-01

25

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

PubMed

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

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

2014-01-01

26

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. PMID:20701771

2010-01-01

27

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

E-print Network

Journal of Theoretical Biology 224 (2003) 269­275 Estimation of effective vaccination rate vaccination is unreliable. For example vaccination against pertussis has comparatively high level of primary and secondary failures. To evaluate efficiency of vaccination we introduce the idea of effective vaccination

Maini, Philip K.

28

Rabies vaccine  

Microsoft Academic Search

Rabies vaccines produced by means of molecular biology are described. Recombinant vaccines employing either viruses as vectors\\u000a (vaccinia, adenovirus, poxvirus, baculovirus, plant viruses) or a plasmid vector carrying the rabies virus glycoprotein gene\\u000a are discussed. Synthetic peptide technology directed to rabies vaccine production is also presented.

Claudio Carlos Paolazzi; Oscar Pérez; Javier De Filippo

1999-01-01

29

Plants as bioreactors for the production of vaccine antigens  

Microsoft Academic Search

Plants have been identified as promising expression systems for commercial production of vaccine antigens. In phase I clinical trials several plant-derived vaccine antigens have been found to be safe and induce sufficiently high immune response. Thus, transgenic plants, including edible plant parts are suggested as excellent alternatives for the production of vaccines and economic scale-up through cultivation. Improved understanding of

Siddharth Tiwari; Praveen C. Verma; Pradhyumna K. Singh; Rakesh Tuli

2009-01-01

30

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 ...

31

SmithKline Beecham Biologicals Worldwide Vaccines  

NSDL National Science Digital Library

This new site from SmithKline Beecham, a "virtual gateway into the world of vaccinology," offers a host of resources on vaccination and vaccine preventable diseases. These resources are organized in three principle sections: Disease, Bio News, and Links. The first and largest section contains various reference resources for ten different diseases or disease groups, which are listed in four columns: disease, virus, epidemiology, and prevention. Although a public site, much of this information is aimed at physicians, health professionals, or other informed users. The Bio News section offers a selection of recent and archived scientific published data from peer-reviewed journals, a select list of links for breaking health news, and recent SmithKline Beecham vaccine press releases. A collection of related annotated links, sorted by country, rounds out the site. An additional site for registered medical professionals only is also available, and these users may log on via the public site. Please note that the site authors indicate that "This site is not intended for US audiences."

32

Cattle Vaccines  

E-print Network

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

Faries Jr., Floron C.

2005-11-11

33

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. PMID:20118381

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

2010-01-01

34

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

PubMed Central

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

Singh, Sarman; Singh, Pragati

2015-01-01

35

Automated production of plant-based vaccines and pharmaceuticals.  

PubMed

A fully automated "factory" was developed that uses tobacco plants to produce large quantities of vaccines and other therapeutic biologics within weeks. This first-of-a-kind factory takes advantage of a plant viral vector technology to produce specific proteins within the leaves of rapidly growing plant biomass. The factory's custom-designed robotic machines plant seeds, nurture the growing plants, introduce a viral vector that directs the plant to produce a target protein, and harvest the biomass once the target protein has accumulated in the plants-all in compliance with Food and Drug Administration (FDA) guidelines (e.g., current Good Manufacturing Practices). The factory was designed to be time, cost, and space efficient. The plants are grown in custom multiplant trays. Robots ride up and down a track, servicing the plants and delivering the trays from the lighted, irrigated growth modules to each processing station as needed. Using preprogrammed robots and processing equipment eliminates the need for human contact, preventing potential contamination of the process and economizing the operation. To quickly produce large quantities of protein-based medicines, we transformed a laboratory-based biological process and scaled it into an industrial process. This enables quick, safe, and cost-effective vaccine production that would be required in case of a pandemic. PMID:23015521

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

2012-12-01

36

Avipoxviruses: infection biology and their use as vaccine vectors  

PubMed Central

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

2011-01-01

37

Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies  

PubMed Central

Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue–derived medical products, human blood components, and animal vaccines. The objective of this study was to determine the potential susceptibility to infection of 5 cell lines used or proposed for manufacture of biological products, as well as other lines. Cell lines were exposed to the infectious agents of sporadic and variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE). Exposed cultures were tested for TSE-associated prion protein (PrPTSE) and TSE infectivity by assay in rodents and nonhuman primates. No PrPTSE or infectivity has been detected in any exposed cell line under study so far. Animals inoculated with BSE brain homogenate developed typical spongiform encephalopathy. In contrast, animals inoculated with cells exposed to the BSE agent remained asymptomatic. All cell lines we studied resisted infection with 3 TSE agents, including the BSE agent. PMID:22172513

Cervenakova, Larisa; Vasilyeva, Irina; Yakovleva, Oksana; Bacik, Igor; Cervenak, Juraj; McKenzie, Carroll; Kurillova, Lubica; Gregori, Luisa; Pomeroy, Kitty; Asher, David M.

2011-01-01

38

STREPTOCOCCUS INIAE EXTRACELLULAR-PRODUCT VACCINE: EVALUATION IN VACCINATION AND CHALLENGE MODEL USING CALCEIN MARKED TILAPIA, OREOCHROMIS NILOTICUS  

Technology Transfer Automated Retrieval System (TEKTRAN)

A Streptococcus iniae extracellular-product vaccine was evaluated in vaccination and challenge model using fluorescent chromophore calcein to non-invasively mark tilapia. The calcein marked, sham-vaccinated (CMSV) tilapia were cohabited with non-marked S. iniae vaccinated (NMV) tilapia in single aq...

39

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

PubMed

Measles and mumps are common viral childhood diseases that can cause serious complications. Vaccination remains the most efficient way to control the spread of these viruses. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblast or primary dog kidney cell substrates, is no longer sufficient. This limitation can be overcome by utilizing other recognized cell substrates such as Madin Darby Canine Kidney (MDCK), Chinese Hamster Ovary (CHO), Vero (monkey origin) cells, MRC-5 (human diploid) or as an alternative, introducing new cell substrates of human or avian origin. A very important factor in vaccine production is the safety and immunogenicity of the final vaccine, where the proper choice of cell substrate used for virus propagation is made. All substrates used in vaccine production must be fully characterized to avoid the contamination of hidden unknown pathogens which is difficult to achieve in primary cell substrates. PMID:23600866

Betáková, T; Svetlíková, D; Gocník, M

2013-01-01

40

Production of a falcon herpesvirus vaccine.  

PubMed

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

Wernery, U; Wernery, R; Kinne, J

1999-09-01

41

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

PubMed Central

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

2014-01-01

42

Hairy roots as a vaccine production and delivery system.  

PubMed

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

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

2013-01-01

43

Biological Effects of Listeriolysin O: Implications for Vaccination  

PubMed Central

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

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

2015-01-01

44

Molecular signatures of antibody responses derived from a systems biological study of 5 human vaccines  

PubMed Central

Many vaccines induce protective immunity via antibodies. Recent studies have used systems biological approaches to determine signatures that predict vaccine immunity in humans, but whether there is a ‘universal signature’ that can predict antibody responses to any vaccine, is unknown. Here we performed systems analyses of immune responses to the meningococcal polysaccharide and conjugate vaccines in healthy adults, in the broader context of our previous studies with the yellow fever and two influenza vaccines. To achieve this, we performed a large-scale network integration of public human blood transcriptomes, and systems-scale databases in specific biological contexts, and deduced a set of blood transcription modules. These modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines providing key insights into primary viral, protein recall and anti-polysaccharide responses. These results illuminate the early transcriptional programs orchestrating vaccine immunity in humans, and demonstrate the power of integrative network modeling. PMID:24336226

Li, Shuzhao; Rouphael, Nadine; Duraisingham, Sai; Romero-Steiner, Sandra; Presnell, Scott; Davis, Carl; Schmidt, Daniel S; Johnson, Scott E; Milton, Andrea; Rajam, Gowrisankar; Kasturi, Sudhir; Carlone, George M; Quinn, Charlie; Chaussabel, Damien; Palucka, A Karolina; Mulligan, Mark J; Ahmed, Rafi; Stephens, David S; Nakaya, Helder I; Pulendran, Bali

2013-01-01

45

Product review on the JE vaccine IXIARO.  

PubMed

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

Firbas, Christa; Jilma, Bernd

2015-02-01

46

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

PubMed Central

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

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

2014-01-01

47

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

PubMed Central

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

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

2013-01-01

48

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

49

IRRIGATION FOR VACCINE PRODUCTION IN PHARMACEUTICAL TOBACCO  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

50

Production of EV71 vaccine candidates.  

PubMed

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

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

2012-12-01

51

Targeting and expression of antigenic proteins in transgenic plants for production of edible oral vaccines  

Microsoft Academic Search

Summary  Exploiting plants as biological bioreactors for production and delivery of edible oral subunit vaccines is a promising application\\u000a of biotechnology. Efforts to enhance expression levels of transgenes coding for antigenic proteins by exploiting promoters,\\u000a targeting sequences, and enhancer elements have produced rather low quantities of the antigen in plant tissues, but enough\\u000a to induce immune responses in feeding studies. This

Schuyler S. Korban

2002-01-01

52

Modeling Shrimp Biomass and Viral Infection for Production of Biological Countermeasures  

E-print Network

Modeling Shrimp Biomass and Viral Infection for Production of Biological Countermeasures H. T 29422 December 9, 2005 Abstract In this paper we develop a mathematical model for the rapid production production with those for vaccine production in shrimp that have been infected with a recombinant viral

53

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

54

Hybrid viral vectors for vaccine and antibody production in plants.  

PubMed

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

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

2013-01-01

55

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

56

New medicinal plants for the production of vaccines  

Microsoft Academic Search

.  During the last decade a large number of biopharmaceuticals has entered the market, mainly protein-based pharmaceuticals like\\u000a hormones, cytokines, antibodies, and vaccines. Several hundred products are currently in clinical trials and already every\\u000a fourth approval for genuinely new pharmaceuticals is made for a recombinant product. To meet the increasing demand for recombinant\\u000a protein production capacity alternative technologies are urgently needed.

K. Glenz; H. Warzecha

2006-01-01

57

Production of RA27/3 rubella vaccine and clinical results with the vaccine.  

PubMed

Adaptation of rubella virus to human diploid cell strains was achieved in 1964, with attenuation in the same cells being accomplished by 1967. The production of rubella vaccine in HDCS is featured by the long period required to build up high titer. High multiplicity of infection gives optimal results. Since rubella virus does not produce a cytopathic effect in HDCS, virus harvests must be made blindly and titrated individually before pooling. A unique feature of this cell-virus relationship is the continuous virus production which takes place for months. For vaccine purposes, however, virus-containing supernatant fluids may be harvested each 48 hrs from the 5th to the 21st day post-infection. Lyophilization presents no particular problems and final titers in ampoules can be as high as 10(5.0) PFU, which represents about 100 subcutaneous doses. Control of rubella vaccine presents only the problem that viral CPE is absent or mild. Therefore the presence or absence of virus may have to be determined by interference. Titration of rubella virus produced in HDCS must be by plaquing in RK13 rabbit kidney cells or by interference in cynomolgus monkey kidney cells. Rubella vaccine (RA27/3 strain) produced in HDCS has been more immunogenic than other strains and retains an ability to infect intranasally as well as subcutaneously. PMID:1031691

Plotkin, S A; Beale, A J

58

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

59

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

60

Designing vaccines based on biology of human dendritic cell subsets  

PubMed Central

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

Palucka, Karolina; Banchereau, Jacques; Mellman, Ira

2010-01-01

61

INVITED REVIEW: TARGETING AND EXPRESSION OF ANTIGENIC PROTEINS IN TRANSGENIC PLANTS FOR PRODUCTION OF EDIBLE ORAL VACCINES  

Microsoft Academic Search

Summary Exploiting plants as biological bioreactors for production and delivery of edible oral subunit vaccines is a promising application of biotechnology. Efforts to enhance expression levels of transgenes coding for antigenic proteins by exploiting promoters, targeting sequences, and enhancer elements have produced rather low quantities of the antigen in plant tissues, but enough to induce immune responses in feeding studies.

SCHUYLER S. KORBAN

62

Production of vaccines against leading biowarfare toxins can utilize DNA scientific technology  

Microsoft Academic Search

There are a significant number of different natural toxins that are potential biological warfare agents against which a vaccine is needed. DNA science has been a key to the development of potential vaccines against the top threat toxin and should contribute such effects for other toxin's vaccines. Several different DNA technological scientific techniques have been used to accomplish the general

John L. Middlebrook

2005-01-01

63

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

64

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

65

Plant expression systems for production of hemagglutinin as a vaccine against influenza virus.  

PubMed

Many examples of a successful application of plant-based expression systems for production of biologically active recombinant proteins exist in the literature. These systems can function as inexpensive platforms for the large scale production of recombinant pharmaceuticals or subunit vaccines. Hemagglutinin (HA) is a major surface antigen of the influenza virus, thus it is in the centre of interests of various subunit vaccine engineering programs. Large scale production of recombinant HA in traditional expression systems, such as mammalian or insect cells, besides other limitations, is expensive and time-consuming. These difficulties stimulate an ever-increasing interest in plant-based production of this recombinant protein. Over the last few years many successful cases of HA production in plants, using both transient and stable expression systems have been reported. Various forms of recombinant HA, including monomers, trimers, virus like particles (VLPs) or chimeric proteins containing its fusion with other polypeptides were obtained and shown to maintain a proper antigenicity. Immunizations of animals (mice, ferrets, rabbits or chickens) with some of these plant-derived hemagglutinin variants were performed, and their effectiveness in induction of immunological response and protection against lethal challenge with influenza virus demonstrated. Plant-produced recombinant subunit vaccines and plant-made VLPs were successfully tested in clinical trials (Phase I and II) that confirmed their tolerance and immunogenicity. PMID:25203219

Redkiewicz, Patrycja; Sirko, Agnieszka; Kamel, Katarzyna Anna; Góra-Sochacka, Anna

2014-01-01

66

Vaccines  

MedlinePLUS Videos and Cool Tools

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

67

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

68

Biological role of surface Toxoplasma gondii antigen in development of vaccine  

PubMed Central

AIM: To analyze the biological role of the surface antigen of Toxoplasma gondii (T gondii) in development of vaccine. METHODS: The surface antigen of T gondii (SAG1) was expressed in vitro. The immune response of the host to the antigen was investigated by detection of specific antibody reaction to SAG1 and production of cytokines. Mice were immunized with recombinant SAG1 and challenged with lethal strain of T gondii RH. The monoclonal antibody to r-SAG1 was prepared and used to study the effects of SAG1 on T gondii tachyzoites under electromicroscope. RESULTS: The mice immunized with recombinant SAG1 delayed death for 60 h compared to the control group. The recombinant SAG1 induced specific high titer of IgG and IgM antibodies as well as IFN-?, IL-2 and IL-4 cytokines in mice. In contrast, IL-12, IL-6 and TNF-? were undetectable. When T gondii tachyzoites were treated with the monoclonal antibody to r-SAG1, the parasites were gathered together, destroyed, deformed, swollen, and holes and gaps formed on the surface. CONCLUSION: SAG1 may be an excellent vaccine candidate against T gondii. The immune protection induced by SAG1 against T gondii may be regulated by both hormone- and cell-mediated immune response. PMID:16688826

Liu, Ke-Yi; Zhang, Dian-Bo; Wei, Qing-Kuan; Li, Jin; Li, Gui-Ping; Yu, Jin-Zhi

2006-01-01

69

9 CFR 114.6 - Mixing biological products.  

Code of Federal Regulations, 2010 CFR

...Animal Products 1 2010-01-01 2010-01-01 false Mixing biological products. 114.6 Section 114.6 Animals...PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in...

2010-01-01

70

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

71

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. PMID:24681843

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

2014-01-01

72

9 CFR 113.3 - Sampling of biological products.  

Code of Federal Regulations, 2011 CFR

...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...samples of Rabies Vaccine, Modified Live Virus; (v) Sixteen samples of all other...Equine Encephalomyelitis Vaccine, Killed Virus; (vii) Twenty-two...

2011-01-01

73

9 CFR 113.3 - Sampling of biological products.  

Code of Federal Regulations, 2013 CFR

...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...samples of Rabies Vaccine, Modified Live Virus; (v) Sixteen samples of all other...Equine Encephalomyelitis Vaccine, Killed Virus; (vii) Twenty-two...

2013-01-01

74

9 CFR 113.3 - Sampling of biological products.  

Code of Federal Regulations, 2014 CFR

...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...samples of Rabies Vaccine, Modified Live Virus; (v) Sixteen samples of all other...Equine Encephalomyelitis Vaccine, Killed Virus; (vii) Twenty-two...

2014-01-01

75

9 CFR 113.3 - Sampling of biological products.  

Code of Federal Regulations, 2010 CFR

...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...samples of Rabies Vaccine, Modified Live Virus; (v) Sixteen samples of all other...Equine Encephalomyelitis Vaccine, Killed Virus; (vii) Twenty-two...

2010-01-01

76

9 CFR 113.3 - Sampling of biological products.  

Code of Federal Regulations, 2012 CFR

...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...samples of Rabies Vaccine, Modified Live Virus; (v) Sixteen samples of all other...Equine Encephalomyelitis Vaccine, Killed Virus; (vii) Twenty-two...

2012-01-01

77

Impact of Methoxymycolic Acid Production by Mycobacterium bovis BCG Vaccines  

PubMed Central

BCG vaccines are a family of closely related daughter strains of an attenuated isolate of Mycobacterium bovis derived by in vitro passage from 1908 to 1921. During subsequent laboratory propagation of the vaccine strain until its lyophilization in 1961, BCG Pasteur underwent at least seven further genomic mutations. The impact of these mutations on the properties of the vaccine is currently unknown. One mutation, a glycine-to-aspartic acid substitution in the mmaA3 gene, occurred between 1927 and 1931 and impairs methoxymycolic acid synthesis in BCG strains obtained from the Pasteur Institute after this period. Mycolic acids of the cell wall are classified into three functional groups (alpha-, methoxy-, and ketomycolic acids), and together these lipids form a highly specialized permeability barrier around the bacterium. To explore the impact of methoxymycolic acid production by BCG strains, we complemented the functional gene of mmaA3 into BCG Denmark and tested a number of in vitro and in vivo phenotypes. Surprisingly, restoration of methoxymycolic acids alone had no effect on cell wall permeability, resistance to antibiotics, or growth in cultured macrophages and C57BL/6 mice. Our results demonstrate that the loss of methoxymycolic acid production did not apparently affect the virulence of BCG strains. PMID:15102790

Belley, Adam; Alexander, David; Di Pietrantonio, Tania; Girard, Manon; Jones, Joses; Schurr, Erwin; Liu, Jun; Sherman, David R.; Behr, Marcel A.

2004-01-01

78

On the optimal production capacity for influenza vaccine.  

PubMed

This paper analyzes the profit maximizing capacity choice of a monopolistic vaccine producer facing the uncertain event of a pandemic in a homogenous population of forward-looking individuals. For any capacity level, the monopolist solves the intertemporal price discrimination problem within the dynamic setting generated by the standard mathematical epidemiological model of infectious diseases. Even though consumers are assumed to be identical, the monopolist will be able to exploit the ex post heterogeneity between infected and susceptible individuals by raising the price of vaccine in response to the increasing hazard rate. The monopolist thus bases its investment decision on the expected profits from the optimal price path given the infection dynamics. It is shown that the monopolist will always choose to invest in a lower production capacity than the social planner. Through numerical simulation, it is demonstrated how the loss to society of having a monopoly producer decreases with the speed of infection transmission. Moreover, it is illustrated how the monopolist's optimal vaccination rate increases as its discount rate rises for cost parameters based on Swedish data. However, the effect of the firm discount rate on its investment decision is sensitive to assumptions regarding the cost of production capacity. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24798081

Forslid, Rikard; Herzing, Mathias

2015-06-01

79

76 FR 3075 - Availability of an Environmental Assessment for Field Testing Feline Leukemia Vaccine, Live...  

Federal Register 2010, 2011, 2012, 2013, 2014

...DEPARTMENT OF AGRICULTURE Animal and Plant Health...Veterinary Biological Product license for this vaccine...veterinary biological product must be shown to be pure, safe, potent, and efficacious...veterinary biological product license may be...

2011-01-19

80

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

PubMed

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

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

2015-01-01

81

Production of potential vaccine against Dermatobia hominis for cattle.  

PubMed

The present study aimed to detect and characterize antigenic proteins and to assess their activity as preventive vaccines against dermatobiosis. Polyclonal antibodies were produced against three larval instars (L(1), L(2), L(3)), and their antigenic proteins were assessed for reactivity. Polyclonal antibodies produced in animals immunized with extracts were analyzed, and L(3)-derived antibodies showed proteins with better antigenic responses. The study of reactivity using immunodetection showed that the 50-kDa protein had the highest antigenicity. This protein was purified and subjected to mass spectrometry, and the sequences obtained were compared with those in the databases available. No similarities were found with existing sequences. Subsequently, large quantities of purified protein were used to immunize cattle. Vaccine effectiveness was evaluated by comparing the number of cutaneous nodules formed in the control group and immunized animals. The antigen produced proved a promising candidate for vaccine production, with 90.67 % efficacy. Immunohistochemistry of antigen-antibody reaction in larval sections showed epitopes all over larval tissues. PMID:22555498

Fernandes, Nelson L M; Zanata, Silvio M; Rönnau, Milton; Soccol, Carlos R; Pandey, Ashok; Thomaz-Soccol, Vanete

2012-06-01

82

Foods as Production and Delivery Vehicles for Human Vaccines  

E-print Network

edible vaccines Vaccination is a great asset for eradication of infectious diseases in humans and animals of antigens in genetically engineered plants provides an inexpensive source of edible vaccines and, in turn, increases the value of plants as novel sources of medicinal drugs. · Edible vaccines against cholera toxin B

Korban, Schuyler S.

83

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

PubMed

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

Rittle, Chad

2014-12-01

84

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. PMID:20822477

Vemula, Sai V.; Mittal, Suresh K.

2010-01-01

85

Therapeutic HIV Vaccines What is a vaccine?  

E-print Network

Therapeutic HIV Vaccines What is a vaccine? A vaccine is a medical product designed to stimulate there are currently no vaccines to prevent or treat HIV, researchers are developing and testing potential HIV vaccines. HIV vaccines designed to prevent HIV infection in HIV negative people are called preventive vaccines

Levin, Judith G.

86

Biological Challenges and Technological Opportunities for Respiratory Syncytial Virus Vaccine Development  

PubMed Central

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

Graham, Barney S.

2011-01-01

87

78 FR 23207 - Availability of an Environmental Assessment for Field Testing of a Yersinia Pestis Vaccine, Live...  

Federal Register 2010, 2011, 2012, 2013, 2014

...DEPARTMENT OF AGRICULTURE Animal and Plant Health...Veterinary Biological Product license for this vaccine...veterinary biological product must be shown to be pure, safe, potent, and efficacious...veterinary biological product license may be...

2013-04-18

88

Vaccinations  

MedlinePLUS

... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. Most pets respond well ...

89

MMR Vaccine (Measles, Mumps, and Rubella)  

MedlinePLUS

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

90

Biological production of products from waste gases  

DOEpatents

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

Gaddy, James L. (Fayetteville, AR)

2002-01-22

91

Glycan analysis in cell culture-based influenza vaccine production: Influence of host cell line and virus strain on the glycosylation pattern of viral hemagglutinin  

Microsoft Academic Search

Mammalian cell culture processes are commonly used for production of recombinant glycoproteins, antibodies and viral vaccines. Since several years there is an increasing interest in cell culture-based influenza vaccine production to overcome limitations of egg-based production systems, to improve vaccine supply and to increase flexibility in vaccine manufacturing. With the switch of the production system several key questions concerning the

Jana Schwarzer; Erdmann Rapp; René Hennig; Yvonne Genzel; Ingo Jordan; Volker Sandig; Udo Reichl

2009-01-01

92

Preventive HIV Vaccines What is a vaccine?  

E-print Network

Preventive HIV Vaccines What is a vaccine? A vaccine is a medical product designed to stimulate infection or make you sick. What is the difference between a preventive HIV vaccine and a therapeutic HIV vaccine? Therapeutic HIV vaccines are designed to control HIV infection in people who are already HIV

Levin, Judith G.

93

Vaccination of seropositive subjects with CHIRON CMV gB subunit vaccine combined with MF59 adjuvant for production of CMV immune globulin.  

PubMed

The safety and immunogenicity of four different regimens of CHIRON cytomegalovirus (CMV) gB subunit vaccine combined with MF59 adjuvant and administered to seropositive plasma donors were evaluated to ascertain whether vaccination of seropositive subjects would significantly increase antibody titer to gB glycoprotein. This was done to select the best vaccination regimen for generating high-titered plasma for manufacture of CMV immune globulin. No serious adverse events were attributed to this vaccine, and the vaccine was well tolerated. Only the first dose of vaccine in each regimen stimulated a four-fold or greater antibody response to gB glycoprotein and each regimen induced similar antibody titers. However, initial vaccination followed by a 1 week rest from plasmapheresis and two booster vaccinations at 8 and 24 weeks, each followed with another 1 week rest from plasmapheresis, maintained the highest geometric mean gB ELISA titer of the four regimens over the 34-week post-vaccination period. CMVIG manufactured from a pool of high titered plasma units from two of four subject groups had gB ELISA and neutralizing antibody titers nine and six times higher, respectively, compared to Cytogam, indicating that vaccination of seropositive subjects with CHIRON gB vaccine combined with MF59 adjuvant prior to harvesting plasma can enhance functional antibody in a CMVIG product. PMID:10733168

Drulak, M W; Malinoski, F J; Fuller, S A; Stewart, S S; Hoskin, S; Duliege, A M; Sekulovich, R; Burke, R; Winston, S

2000-01-01

94

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

95

Transgenic plants for the production of veterinary vaccines  

Microsoft Academic Search

The expression of antigens in transgenic plants has been increasingly used in the development of experimental vaccines, particularly oriented to the development of edible vaccines. Hence, this technology becomes highly suitable to express immunogenic proteins from pathogens. Foot and mouth disease virus, bovine rotavirus and bovine viral diarrhoea virus are considered to be the most important causative agents of economic

María José Dus Santos; Andrés Wigdorovitz

2005-01-01

96

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. PMID:24822195

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

2014-01-01

97

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

PubMed

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

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

2014-01-01

98

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

PubMed

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

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

2012-05-01

99

Vaccination Mathematics  

E-print Network

Vaccination Strategies for Epidemic Models Douglas B. Meade Department of Mathematics University://www.math.sc.edu/~meade/ 27 May 1999 #12; May 1999 IMA Mathematical Biology Seminar 0 Vaccination Strategies for Epidemic and natural death -- no death from infection -- no vaccination Ref: Shulgin, Stone, and Agur, Bull Math Bio

Meade, Douglas B.

100

9 CFR 112.6 - Packaging biological products.  

Code of Federal Regulations, 2010 CFR

...the filed Outline of Production. Each multiple-dose...the filed Outline of Production for the number of doses...Poultry products for mass administration (including...and products used in automatic vaccinating systems...the filed Outline of Production. Poultry...

2010-01-01

101

Packet Vaccine: Black-box Exploit Detection and Signature Generation  

E-print Network

Packet Vaccine: Black-box Exploit Detection and Signature Generation XiaoFeng Wang, Zhuowei Li Youl Choi Indiana University jychoi@indiana.edu ABSTRACT In biology, a vaccine is a weakened strain antibody production. Inspired by this idea, we propose a packet vaccine mechanism that ran- domizes address

Reiter, Michael

102

Biological hydrogen production; fundamentals and limiting processes  

Microsoft Academic Search

Biological hydrogen production has been known for over a century and research directed at applying this process to a practical means of hydrogen fuel production has been carried out for over a quarter century. The various approaches that have been proposed and investigated are reviewed and critical limiting factors identified. The low energy content of solar irradiation dictates that photosynthetic

Patrick C. Hallenbeck; John R. Benemann

2002-01-01

103

Vaccination of biological cellulose fibers with glucose: a gateway to novel nanocomposites.  

PubMed

This work introduces, for the first time worldwide, the means to preserve and protect the natural nanoporous structure of the never-dried plant cell wall, against the irreversible collapse, which occurs due to drying. Simultaneously, these means, used for the above-mentioned aim, provide a gateway to novel nanocomposite materials, which retain the super reactive and super absorbent properties of the never-dried biological cellulose fibers. The present work showed, for the first time worldwide, that glucose can be vaccinated into the cell wall micropores or nanostructure of the never-dried biological cellulose fibers, by simple new techniques, to create a reactive novel nanocomposite material possessing surprising super absorbent properties. Inoculation of the never dried biological cellulose fibers, with glucose, prevented the collapse of the cell wall nanostructure, which normally occurs due to drying. The nanocomposite, produced after drying of the glucose inoculated biological cellulose, retained the super absorbent properties of the never dried biological cellulose fibers. It was found that glucose under certain circumstances grafts to the never dried biological cellulose fibers to form a novel natural nanocomposite material. About 3-8% (w/w) glucose remained grafted in the novel nanocomposite. PMID:17950824

Fahmy, Tamer Y A; Mobarak, Fardous

2008-01-01

104

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

105

Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults.  

PubMed

We evaluated in vivo innate immune responses in monocyte populations from 67 young (aged 21-30 years) and older (aged ?65 years) adults before and after influenza vaccination. CD14(+)CD16(+) inflammatory monocytes were induced after vaccination in both young and older adults. In classical CD14(+)CD16(-) and inflammatory monocytes, production of tumor necrosis factor ? and interleukin 6, as measured by intracellular staining, was strongly induced after vaccination. Cytokine production was strongly associated with influenza vaccine antibody response; the highest levels were found as late as day 28 after vaccination in young subjects and were substantially diminished in older subjects. Notably, levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were markedly elevated in monocytes from older subjects before and after vaccination. In purified monocytes, we found age-associated elevation in phosphorylated signal transducer and activator of transcription-3, and decreased serine 359 phosphorylation of the negative IL-10 regulator dual-specificity phosphatase 1. These findings for the first time implicate dysregulated IL-10 production in impaired vaccine responses in older adults. PMID:25367297

Mohanty, Subhasis; Joshi, Samit R; Ueda, Ikuyo; Wilson, Jean; Blevins, Tamara P; Siconolfi, Barbara; Meng, Hailong; Devine, Lesley; Raddassi, Khadir; Tsang, Sui; Belshe, Robert B; Hafler, David A; Kaech, Susan M; Kleinstein, Steven H; Trentalange, Mark; Allore, Heather G; Shaw, Albert C

2015-04-01

106

IRRIGATION TO MAXIMIZE VACCINE ANTIGEN PRODUCTION IN PHARMACEUTICAL TOBACCO  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

107

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

108

ECVAM's contributions to the implementation of the Three Rs in the production and quality control of biologicals.  

PubMed

A summary is presented of the activities initiated, and the progress achieved, between April 1993 and December 2001 in implementing the Three Rs in one of the main priority areas of the European Centre for the Validation of Alternative Methods (ECVAM) - the production and quality control of biologicals. These have included organising eight key workshops, and financial contributions to, and sponsorship of, relevant international workshops, symposia and conferences. Noteworthy activities include financial support and/or participation in a number of prevalidation and validation studies. These involved alternative methods for the batch potency testing of: human tetanus vaccines; human and veterinary tetanus antisera and immunoglobulin; rabies vaccines; Leptospira hardjo vaccines; Clostridium perfringens vaccines; and erysipelas vaccines. They also involved a cell culture test for specific toxicity testing of diphtheria toxoid vaccines. In addition, ECVAM funded a study on the use of humane endpoints for vaccine quality control tests involving severe suffering, such as the potency testing of erysipelas, rabies and pertussis vaccines. ECVAM has also contributed financially to the compilation of manuals and expert reports, and to training in test methods. Following the report of an ECVAM Task Force, ECVAM financially supported the prevalidation of some in vitro methods for the potency testing of a recombinant hormone. A proposal is presented for promotion of regulatory acceptance, and suggestions are made for possible future activities. PMID:11827574

Halder, Marlies; Hendriksen, Coenraad; Cussler, Klaus; Balls, Michael

2002-01-01

109

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

PubMed

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

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

2011-07-01

110

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

PubMed

Stable integration of a gene into the plant nuclear or chloroplast genome can transform higher plants (e.g. tobacco, potato, tomato, banana) into bioreactors for the production of subunit vaccines for oral or parental administration. This can also be achieved by using recombinant plant viruses as transient expression vectors in infected plants. The use of plant-derived vaccines may overcome some of the major problems encountered with traditional vaccination against infectious diseases, autoimmune diseases and tumours. They also offer a convenient tool against the threat of bio-terrorism. State of the art, experimental strategies, safety and perspectives are discussed in this article. PMID:12531364

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

2003-01-30

111

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. PMID:20846415

2010-01-01

112

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

Microsoft Academic Search

The effect of selenium (Se) and vitamin E (vit E) on antibody production of sheep vaccinated against Chlamydia psittaci (ovis) was investigated. Thirty-two sheep, one year old, seronegative to Chlamydia infection, vaccinated against enterotoxemia and dewormed were used.Injectable sodium selenite (0.1 mg\\/kg b.w.) was given twice to animals of the first group (gSe), with a three week interval. The sheep

N. Giadinis; G. Koptopoulos; N. Roubies; V. Siarkou; A. Papasteriades

2000-01-01

113

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

PubMed Central

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

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

2015-01-01

114

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

PubMed

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

1995-10-01

115

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. PMID:19918215

Philbin, Victoria Jane; Levy, Ofer

2009-01-01

116

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

PubMed Central

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

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

2014-01-01

117

Harnessing the Biological Activity of Natural Products  

Cancer.gov

Researchers have been intrigued by the potent and beneficial biological activity shown by some natural products and are testing ways to incorporate them into standard and experimental cancer treatment regimens, both to enhance the anticancer effects of therapy and reduce side effects.

118

Advances in host and vector development for the production of plasmid DNA vaccines.  

PubMed

Recent developments in DNA vaccine research provide a new momentum for this rather young and potentially disruptive technology. Gene-based vaccines are capable of eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria, and tuberculosis, for which the conventional vaccine technologies have failed so far. The recent identification and characterization of genes coding for tumor antigens has stimulated the development of DNA-based antigen-specific cancer vaccines. Although most academic researchers consider the production of reasonable amounts of plasmid DNA (pDNA) for immunological studies relatively easy to solve, problems often arise during this first phase of production. In this chapter we review the current state of the art of pDNA production at small (shake flasks) and mid-scales (lab-scale bioreactor fermentations) and address new trends in vector design and strain engineering. We will guide the reader through the different stages of process design starting from choosing the most appropriate plasmid backbone, choosing the right Escherichia coli (E. coli) strain for production, and cultivation media and scale-up issues. In addition, we will address some points concerning the safety and potency of the produced plasmids, with special focus on producing antibiotic resistance-free plasmids. The main goal of this chapter is to make immunologists aware of the fact that production of the pDNA vaccine has to be performed with as much as attention and care as the rest of their research. PMID:24619702

Mairhofer, Juergen; Lara, Alvaro R

2014-01-01

119

New advances in the production of edible plant vaccines: chloroplast expression of a tetanus vaccine antigen, TetC  

Microsoft Academic Search

Vaccines are a proven method of controlling disease. However there are issues with the delivery and administration of vaccines. A particular problem is that the majority of vaccines currently used are injected, which can be unsafe if needles are reused in areas where blood-borne diseases are prevalent. Vaccines targeting the mucosal immune system avoid many of the problems associated with

John Tregoning; Pal Maliga; Gordon Dougan; Peter J. Nixon

2004-01-01

120

Edible vaccines.  

PubMed Central

Vaccines were the result of trial and error research until molecular biology and genetic engineering made possible the creation of of many new and improved vaccines. New vaccines need to be inexpensive, easily administered, and capable of being stored and transported without refrigeration; without these characteristics, developing countries find it difficult to adopt vaccination as the central strategy for preventing their most devastating diseases. The authors describe a promising approach to inexpensive and effective vaccines: producing them in plants we commonly consume. Images p190-a p191-a p193-a p196-a PMID:9182305

Artnzen, C J

1997-01-01

121

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

PubMed

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

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

2015-04-01

122

Novel suspension cell-based vaccine production systems for Rift Valley fever virus-like particles.  

PubMed

Rift Valley fever virus (RVFV) is an arthropod-borne pathogen that often results in severe morbidity and mortality in both humans and livestock. As its geographic range continues to expand, it presents a real threat to naïve populations around the world by accidental introduction (e.g., the result of increased travel) or intentional release (e.g., a bioterror event). While there is a clear need for a safe and efficacious vaccine against this emerging and re-emerging pathogen, no FDA-approved vaccine is currently available. This need was addressed by the establishment of novel mammalian and insect suspension cell line systems for the efficient production of RVF virus-like particle (VLP)-based vaccine candidates. A direct comparison of the production of RVF VLPs in these systems was performed. Optimization and characterization resulted in a production platform suitable for scale-up. Furthermore, RVF VLP-based vaccines were tested in a lethal challenge model and showed full protection, demonstrating that RVF VLPs present promising RVFV vaccine candidates. PMID:20655330

Mandell, Robert B; Koukuntla, Ramesh; Mogler, Laura J K; Carzoli, Andrea K; Holbrook, Michael R; Martin, Brian K; Vahanian, Nicholas; Link, Charles J; Flick, Ramon

2010-11-01

123

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

E-print Network

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

Barthelat, Francois

124

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

125

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. PMID:24032031

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

2013-01-01

126

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

PubMed Central

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

Perozo, Francisco; Marcano, Rosmar

2012-01-01

127

Research advances on transgenic plant vaccines.  

PubMed

In recent years, with the development of genetics molecular biology and plant biotechnology, the vaccination (e.g. genetic engineering subunit vaccine, living vector vaccine, nucleic acid vaccine) programs are taking on a prosperous evolvement. In particular, the technology of the use of transgenic plants to produce human or animal therapeutic vaccines receives increasing attention. Expressing vaccine candidates in vegetables and fruits open up a new avenue for producing oral/edible vaccines. Transgenic plant vaccine disquisitions exhibit a tempting latent exploiting foreground. There are a lot of advantages for transgenic plant vaccines, such as low cost, easiness of storage, and convenient immune-inoculation. Some productions converged in edible tissues, so they can be consumed directly without isolation and purification. Up to now, many transgenic plant vaccine productions have been investigated and developed. In this review, recent advances on plant-derived recombinant protein expression systems, infectious targets, and delivery systems are presented. Some issues of high concern such as biosafety and public health are also discussed. Special attention is given to the prospects and limitations on transgenic plant vaccines. PMID:16625826

Han, Mei; Su, Tao; Zu, Yuan-Gang; An, Zhi-Gang

2006-04-01

128

Flow cytometric monitoring of influenza A virus infection in MDCK cells during vaccine production  

Microsoft Academic Search

BACKGROUND: In cell culture-based influenza vaccine production the monitoring of virus titres and cell physiology during infection is of great importance for process characterisation and optimisation. While conventional virus quantification methods give only virus titres in the culture broth, data obtained by fluorescence labelling of intracellular virus proteins provide additional information on infection dynamics. Flow cytometry represents a valuable tool

Josef Schulze-Horsel; Yvonne Genzel; Udo Reichl

2008-01-01

129

Vaccine Policy in India  

Microsoft Academic Search

India enjoyed early initial successes in vaccine development and indigenous production of vaccines in the public sector. But the country now faces a growing gap between the demand for and supply of essential vaccines.

Yennapu Madhavi

2005-01-01

130

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. PMID:22221832

Winter, Jaclyn M; Tang, Yi

2012-01-01

131

History of vaccination  

PubMed Central

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

Plotkin, Stanley

2014-01-01

132

Limited In Vivo Production of Type I or Type III Interferon After Infection of Macaques with Vaccine or Wild-Type Strains of Measles Virus.  

PubMed

The innate immune response to viral infections often includes induction of types I and III interferons (IFNs) and production of antiviral proteins. Measles is a severe virus-induced rash disease, but in vitro studies suggest that in the absence of defective interfering RNAs, neither wild-type (WT) nor vaccine strains of measles virus (MeV) induce IFN. To determine whether IFN is produced in vivo, we studied tissues from macaques infected with vaccine or WT strains of MeV using quantitative reverse transcriptase-polymerase chain reaction to assess levels of IFN and IFN-stimulated gene (ISG) mRNAs and a flow cytometry-based bioassay to assess levels of biologically active IFN. There was little to no induction of type I IFN, type III IFN, Mx, or ISG56 mRNAs in monkeys infected with vaccine or WT MeV and no IFN detection by bioassay. Therefore, the innate responses to infection with vaccine or WT strains of MeV are not dependent on IFN production. PMID:25517681

Shivakoti, Rupak; Hauer, Debra; Adams, Robert J; Lin, Wen-Hsuan W; Duprex, William Paul; de Swart, Rik L; Griffin, Diane E

2015-04-01

133

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. PMID:23300558

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

2012-01-01

134

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

PubMed Central

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

2012-01-01

135

DNA vaccines  

NASA Astrophysics Data System (ADS)

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

Gregersen, Jens-Peter

2001-12-01

136

Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.  

PubMed

We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239?nef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1. PMID:25135832

Li, Qingsheng; Zeng, Ming; Duan, Lijie; Voss, James E; Smith, Anthony J; Pambuccian, Stefan; Shang, Liang; Wietgrefe, Stephen; Southern, Peter J; Reilly, Cavan S; Skinner, Pamela J; Zupancic, Mary L; Carlis, John V; Piatak, Michael; Waterman, Diane; Reeves, R Keith; Masek-Hammerman, Katherine; Derdeyn, Cynthia A; Alpert, Michael D; Evans, David T; Kohler, Heinz; Müller, Sybille; Robinson, James; Lifson, Jeffrey D; Burton, Dennis R; Johnson, R Paul; Haase, Ashley T

2014-09-15

137

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

138

Growth conditions of clostridium perfringens type B for production of toxins used to obtain veterinary vaccines.  

PubMed

The diseases caused for Clostridium perfringens are generically called enterotoxemias because toxins produced in the intestine may be absorbed into the general circulation. C. perfringens type B, grown in batch fermentation, produced toxins used to obtain veterinary vaccines. Glucose in concentrations of 1.4-111.1 mM was used to define the culture medium. The minimum concentration for a satisfactory production of vaccines against clostridial diseases was 55.6 mM. Best results were brought forth by meat and casein peptones, both in the concentration 5.0 g l(-1) in combination with glucose and a culture pH maintained at 6.5 throughout the fermentation process. The production of lactic, acetic and propionic organic acids was observed. Ethanol was the metabolite produced in the highest concentration when cultures maintained steady pH of 6.5 with exception of cultures with initial glucose concentration of 1.4 mM, where the highest production was of propionic acid. Maximal cell concentration and the highest toxin title concomitantly low yield coefficient to organic acids and ethanol were obtained using basal medium containing 111.1 mM glucose under a controlled pH culture (pH) 6.5 in batch fermentations of C. perfringens type B. These data contribute to improve process for industrial toxin production allowing better condition to produce a toxoid vaccine. PMID:24573216

Viana Brandi, Igor; Domenici Mozzer, Otto; Jorge, Edson Vander; Vieira Passos, Frederico Jose; Lopes Passos, Flavia Maria; Cangussu, Alex Sander Rodrigues; Macedo Sobrinho, Eliane

2014-09-01

139

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

PubMed

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

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

2014-02-01

140

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

141

Use of Plant Viruses for Production of Plant-Derived Vaccines  

Microsoft Academic Search

Plants produce appropriately folded, post-translationally processed proteins that, as antigens, elicit efficacious immune responses in preclinical animal models and antigen-specific responses in humans. Plant-produced vaccine candidates have been produced using transgenic technologies and the utilization of plant viruses for the transient protein expression. The later approach has numerous advantages in recombinant protein production, including rapid protein expression and higher yields

Laurence K. Grill; Kenneth E. Palmer; Gregory P. Pogue

2005-01-01

142

[Screening for opportunistic infections and vaccination before introduction of biologic therapy].  

PubMed

Patients on anti-TNFalpha medications carry a higher risk for developing opportunistic infections. In order to introduce anti-TNFalpha therapy, screening for hepatitis viruses B and C, HIV, EBV, HPV, TBC, bacterial, fungal and parasitic infections should be performed. Screening involves patient's history of earlier infectious diseases, vaccinations and traveling to parts of the world with endemic diseases. Clinical examination should be supplemented with stomatologic and gynecologic exams. Laboratory results include leukogram, transaminases, C-reactive protein, urine analysis, hepatitis B, C, HIV and EBV serology. Varicella zoster virus serology depends on past medical history. If the patient has traveled to tropical areas, both stool analysis and strongiloidiasis serology should be performed. Other mandatory examinations include chest radiography, PPD and TBC serology using interferon gamma release test (IGRA). If suspecting intra-abdominal abscess, magnetic resonance of the abdomen is recommended. In case of abscess, CMV or Clostridium difficile colitis anti-TNF-alpha therapy is contraindicated. Live vaccine application is contraindicated in patients receiving anti-TNFalpha therapy. All seronegative patients should be vaccinated against hepatitis B virus. Seasonal flu vaccination is recommended to be applicated yearly and pneumococcal polysaccharide vaccine once in every five years. Based on the past medical history and serologic results, patients are vaccinated against VZV with extra precaution. Human papilloma virus vaccination is performed in a group of women under 23 years of age, after gathering cervical smear sample analysis. PMID:24471299

Sinci?, Brankica Mijandrusi?; Vince, Adriana

2013-04-01

143

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

PubMed

Leptospira borgpetersenii serovar Hardjo subtype Hardjobovis (Hardjobovis) is the main causative agent of bovine leptospirosis in Australia, New Zealand, North America and elsewhere. Bovine leptospirosis can result in spontaneous abortion, stillbirth and reduced milk output. The organism is shed in the urine of infected animals and contact with contaminated materials can result in zoonotic infections in humans. Protective immunity in cattle against Hardjobovis involves stimulation of a Th1 cell mediated immune response, which can be characterized by the production of IFN-? when blood from vaccinated animals is exposed to Hardjobovis antigens. However, the leptospiral components involved in stimulating this response have yet to be identified. In this study, 238 recombinant leptospiral proteins were evaluated for their ability to stimulate IFN-? production in blood of cattle vaccinated with a commercial monovalent Hardjobovis vaccine. The conserved lipoprotein LipL32 is the major outer membrane protein of pathogenic Leptospira spp. A pool of soluble recombinant proteins which included LipL32, as well as LipL32 alone, stimulated significant IFN-? production in blood of vaccinated cattle. A number of recombinant LipL32 fragments was generated, which identified the amino acids between 20 and 200 as containing the bovine T-cell reactive regions of LipL32. However, whether LipL32 plays a role in stimulating protective immunity in mammals has yet to be conclusively determined. PMID:24467929

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

2014-03-14

144

Defossiling Fuel: How Synthetic Biology Can Transform Biofuel Production  

E-print Network

Defossiling Fuel: How Synthetic Biology Can Transform Biofuel Production David F. Savage , Jeffrey through natural intermediates to final molecule is long, and biofuel production is perhaps the ultimate engineering, economic, political, and environmental realities. Are biofuels sustainable? Consider U

145

77 FR 22282 - Draft Guidelines on Biologics Quality Monitoring: Testing for the Detection of Mycoplasma...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Draft Guidelines on Biologics Quality Monitoring: Testing for the Detection...apply to final product and master seed/cell testing in veterinary vaccines...biological products through the master seeds, the master cell seed (stock), starting...

2012-04-13

146

Systems biological approaches to measure and understand vaccine immunity in humans  

PubMed Central

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

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

2013-01-01

147

Biological treatment of shrimp production wastewater.  

PubMed

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

Boopathy, Raj

2009-07-01

148

The risks posed by the importation of animals vaccinated against foot and mouth disease and products derived from vaccinated animals: a review.  

PubMed

The Terrestrial Animal Health Code of the OIE (World organisation for animal health) (the Terrestrial Code) makes recommendations for international movements of live animals and animal products because of a possible generic risk of foot and mouth disease (FMD) for these different commodities. For instance, international movement of vaccinated live animals or products of such animals is restricted due to the possible masking of clinical disease as a result of vaccination and to the perceived risk of persistently infected animals among vaccinated livestock. In addition, bilateral agreements between exporting and importing countries on the importation of animal products can be based on the 'equivalence' of the animal health conditions in both countries, or on formal or informal risk assessments in accordance with the norms and recommendations of the Terrestrial Code. In this regard, an exporting country may be required to prepare a complete and transparent document describing the animal health situation, including the factors required to assess the risk involved. Furthermore, expert committees of importing countries regularly evaluate and verify these conditions in exporting countries. The level of confidence in the information obtained by the expert committee can then be entered into the risk analysis equation. An important FMD risk reduction factor for the importation of animals and animal products is early recognition of the disease at the source of the commodity by alert stakeholders, such as official and private veterinarians and the chain of the livestock industry. This is true for all countries irrespective of their vaccination status. The risk posed by the importation of vaccinated animals becomes negligible when an adequate protocol--in compliance with the norms and recommendations of the Terrestrial Code--is applied. However, recently, export of live animals from countries that do not practise vaccination has also proven to pose a significant risk and the rules governing such transport may have to be reviewed. Disease surveillance, biosecurity at the farm level, traceability and control of the source cattle and slaughterhouse inspections are the main risk reduction measures for meat and meat products from vaccinated cattle. If these animals are slaughtered and processed under good management practice--in accordance with the norms and recommendations of the Terrestrial Code--these products present a negligible risk for the introduction of FMD. Risk reduction by maturation and deboning is an important procedure, but is probably overemphasised. Mechanical contamination of cattle carcasses with 'carrier virus' from the pharyngeal area during slaughter and processing is very unlikely. Risk assessments showed that the importation of milk products from countries or zones that practise vaccination of dairy herds poses a negligible risk. Risk assessments also demonstrated that the importation of bovine embryos from vaccinated cows--in accordance with the norms and recommendations of the Terrestrial Code--poses a negligible risk. Likewise, the risk from the importation of semen from vaccinated bulls is also negligible when an adequate test protocol is applied in accordance with the Terrestrial Code. PMID:15005540

Sutmoller, P; Casas Olascoaga, R

2003-12-01

149

WHO activities towards the three Rs in the development and control of biological products.  

PubMed

WHO supports the concept of replacement, reduction and refinement of the use of in vivo methods for biologicals production and control, and regularly conducts reviews of its recommended procedures to allow reduction in the use of animals. The coordination of collaborative studies, publication of standardized methods, and holding of workshops on the use of these methods contributes to their use. The neurovirulence test for oral poliovaccine is probably the single most visible animal test for which alternative methods are sought. Collaborative studies on alternative methods for screening products are currently being sponsored by WHO. The use of Vero cells rather than primary monkey kidney cells for poliovaccine production can avoid the use of many monkeys. Cell banks of Vero and HEp-2 cells have been developed by WHO, tested for virus sensitivity and freedom from adventitious agents, and are available for vaccine production and control, replacing primary animal cells. For the future, final product testing will increasingly be directed towards establishment of consistency of production rather than potency. By supporting the validation and use of this approach, WHO can effectively influence more rational animal use in biological production and control. PMID:8785961

Milstien, J; Grachev, V; Padilla, A; Griffiths, E

1996-01-01

150

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

PubMed

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

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

2012-01-20

151

Research Advances on Transgenic Plant Vaccines  

Microsoft Academic Search

In recent years, with the development of genetics molecular biology and plant biotechnology, the vaccination (e.g. genetic engineering subunit vaccine, living vector vaccine, nucleic acid vaccine) programs are taking on a prosperous evolvement. In particular, the technology of the use of transgenic plants to produce human or animal therapeutic vaccines receives increasing attention. Expressing vaccine candidates in vegetables and fruits

Mei HAN; Tao SU; Yuan-Gang ZU; Zhi-Gang AN

2006-01-01

152

Rapid production of a H9N 2 influenza vaccine from MDCK cells for protecting chicken against influenza virus infection.  

PubMed

H9N2 subtype avian influenza viruses are widespread in domestic poultry, and vaccination remains the most effective way to protect the chicken population from avian influenza pandemics. Currently, egg-based H9N2 influenza vaccine production has several disadvantages and mammalian MDCK cells are being investigated as candidates for influenza vaccine production. However, little research has been conducted on low pathogenic avian influenza viruses (LPAIV) such as H9N2 replicating in mammalian cells using microcarrier beads in a bioreactor. In this study, we present a systematic analysis of a safe H9N2 influenza vaccine derived from MDCK cells for protecting chickens against influenza virus infection. In 2008, we isolated two novel H9N2 influenza viruses from chickens raised in southern China, and these H9N2 viruses were adapted to MDCK cells. The H9N2 virus was produced in MDCK cells in a scalable bioreactor, purified, inactivated, and investigated for use as a vaccine. The MDCK-derived H9N2 vaccine was able to induce high titers of neutralizing antibodies in chickens of different ages. Histopathological examination, direct immunofluorescence, HI assay, CD4(+)/CD8(+) ratio test, and cytokine evaluation indicated that the MDCK-derived H9N2 vaccine evoked a rapid and effective immune response to protect chickens from influenza infection. High titers of H9N2-specific antibodies were maintained in chickens for 5 months, and the MDCK-derived H9N2 vaccine had no effects on chicken growth. The use of MDCK cells in bioreactors for LPAIV vaccine production is an attractive option to prevent outbreaks of LPAIV in poultry. PMID:25646963

Ren, Zhenghua; Lu, Zhongzheng; Wang, Lei; Huo, Zeren; Cui, Jianhua; Zheng, Tingting; Dai, Qing; Chen, Cuiling; Qin, Mengying; Chen, Meihua; Yang, Rirong

2015-04-01

153

[Abnormal toxicity - a relevant safety test under GLP- and GMP-conditions in the production of vaccines?  

PubMed

The German Pharmacopoeia requires a test for abnormal toxicity in mice and guinea pigs as an unspecific safety test for vaccines and sera. This paper deals with the relevance of abnormal toxicity after the introduction of GMP- and GLP-conditions in the production of veterinary biologicals. Preliminary results: 1.The evidence of the test on abnormal toxicity as a prediction for (harmful) batches is insufficient, because a) the specificity is missing b) misinterpretations of reactions caused by compounds in mice and guinea pigs are possible which are independent of the innocuity of the medical products for the target animal. 2.The concentration of adjuvants and preservatives frequently leads to local and/or generalized symptoms of incompatibility with minor relevance to the target species. 3.The large number of animals used for this test and the suffering during the procedure is not justified in view of the negligible increase of safety of the product. Therefore the test for abnormal toxicity should be removed from the Pharmacopoeia. PMID:11178400

Duchow, Karin; Krämer, Beate

1994-01-01

154

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

Microsoft Academic Search

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

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

2007-01-01

155

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

Microsoft Academic Search

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

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

2000-01-01

156

RNAi suppression of rice endogenous storage proteins enhances the production of rice-based Botulinum neutrotoxin type A vaccine.  

PubMed

Mucosal vaccines based on rice (MucoRice) offer a highly practical and cost-effective strategy for vaccinating large populations against mucosal infections. However, the limitation of low expression and yield of vaccine antigens with high molecular weight remains to be overcome. Here, we introduced RNAi technology to advance the MucoRice system by co-introducing antisense sequences specific for genes encoding endogenous rice storage proteins to minimize storage protein production and allow more space for the accumulation of vaccine antigen in rice seed. When we used RNAi suppression of a combination of major rice endogenous storage proteins, 13 kDa prolamin and glutelin A in a T-DNA vector, we could highly express a vaccine comprising the 45 kDa C-terminal half of the heavy chain of botulinum type A neurotoxin (BoHc), at an average of 100 ?g per seed (MucoRice-BoHc). The MucoRice-Hc was water soluble, and was expressed in the cytoplasm but not in protein body I or II of rice seeds. Thus, our adaptation of the RNAi system improved the yield of a vaccine antigen with a high molecular weight. When the mucosal immunogenicity of the purified MucoRice-BoHc was examined, the vaccine induced protective immunity against a challenge with botulinum type A neurotoxin in mice. These findings demonstrate the efficiency and utility of the advanced MucoRice system as an innovative vaccine production system for generating highly immunogenic mucosal vaccines of high-molecular-weight antigens. PMID:22554467

Yuki, Yoshikazu; Mejima, Mio; Kurokawa, Shiho; Hiroiwa, Tomoko; Kong, Il Gyu; Kuroda, Masaharu; Takahashi, Yoko; Nochi, Tomonori; Tokuhara, Daisuke; Kohda, Tomoko; Kozaki, Shunji; Kiyono, Hiroshi

2012-06-13

157

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

E-print Network

............................................................................................................... 73 ix FIGURE Page 28 Least squares means for serum neutralizing antibody titers to bovine viral diarrhea virus type 1... Serum neutralizing antibody titer response to inoculation with BVD type 2 in steers vaccinated with Arsenal 4.1, Vista SQ, or physiological saline over 42 d...

Horne, Willy J.

2010-01-16

158

Shear effects on aluminum phosphate adjuvant particle properties in vaccine drug products.  

PubMed

Adjuvant-containing drug products can be exposed to high levels of interfacial shear during manufacture. This may affect the integrity of the adjuvant, alter its interaction with the drug substance or change the physical characteristics of the drug product. In this study, a solid-liquid interfacial shear device was used to investigate the shear response of aluminum phosphate adjuvant alone and two adjuvant containing vaccine drug products (DP1 and DP2). The relationship between the shear sensitivity of each and its resuspension properties was determined. Changes in the particle dimensions of the bulk adjuvant were minimal at shear strain rates of 10,900 s(-1) . However, at 25,500 s(-1) , the median particle diameter was reduced from 6.2 to 3.5 ?m and was marked by the presence of sub-micron fines. A formulation without drug substance and DP2 produced similar shear responses but with less impact on particle diameter. The behavior of DP1 was less predictable. Sheared DP1 was characterized by prolonged sedimentation because of the presence of fine particulates and required in excess of 300 rotations to resuspend after extended storage. The study confirms that the solid-liquid interfacial shear device may be applied to understand product shear sensitivity associated with vaccine manufacturing. PMID:25175154

Kolade, Olatomirin O; Jin, Wenbin; Tengroth, Charbel; Green, Kenneth D; Bracewell, Daniel G

2015-02-01

159

The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines.  

PubMed

Influenza viruses for vaccine production are currently grown on embryonated eggs. This manufacturing system conveys many major drawbacks such as inflexibility, cumbersome down stream processing, inability of some strains to replicate on eggs to high enough yields, and selection of receptor-binding variants with reduced antigenicity. These limitations emphasize the need for a cell line-based production system that could replace eggs in the production of influenza virus vaccines in a pandemic proof fashion. Here we present the efficient propagation of influenza A and B viruses on the fully characterized and standardized human cell line PER.C6. PMID:11257414

Pau, M G; Ophorst, C; Koldijk, M H; Schouten, G; Mehtali, M; Uytdehaag, F

2001-03-21

160

Biological control and sustainable food production.  

PubMed

The use of biological control for the management of pest insects pre-dates the modern pesticide era. The first major successes in biological control occurred with exotic pests controlled by natural enemy species collected from the country or area of origin of the pest (classical control). Augmentative control has been successfully applied against a range of open-field and greenhouse pests, and conservation biological control schemes have been developed with indigenous predators and parasitoids. The cost-benefit ratio for classical biological control is highly favourable (1:250) and for augmentative control is similar to that of insecticides (1:2-1:5), with much lower development costs. Over the past 120 years, more than 5000 introductions of approximately 2000 non-native control agents have been made against arthropod pests in 196 countries or islands with remarkably few environmental problems. Biological control is a key component of a 'systems approach' to integrated pest management, to counteract insecticide-resistant pests, withdrawal of chemicals and minimize the usage of pesticides. Current studies indicate that genetically modified insect-resistant Bt crops may have no adverse effects on the activity or function of predators or parasitoids used in biological control. The introduction of rational approaches for the environmental risk assessment of non-native control agents is an essential step in the wider application of biological control, but future success is strongly dependent on a greater level of investment in research and development by governments and related organizations that are committed to a reduced reliance on chemical control. PMID:17827110

Bale, J S; van Lenteren, J C; Bigler, F

2008-02-27

161

The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines  

Microsoft Academic Search

Influenza viruses for vaccine production are currently grown on embryonated eggs. This manufacturing system conveys many major drawbacks such as inflexibility, cumbersome down stream processing, inability of some strains to replicate on eggs to high enough yields, and selection of receptor-binding variants with reduced antigenicity. These limitations emphasize the need for a cell line-based production system that could replace eggs

M. G. Pau; C. Ophorst; M. H. Koldijk; G. Schouten; M. Mehtali; F. Uytdehaag

2001-01-01

162

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

PubMed Central

Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1) gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM) were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 ?g/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the first time the production of Influenza viruses using Vero cells in commercially available animal-component free, serum-free medium. This work can be used as a basis for efficient production of attenuated as well as wild type Influenza virus for research and vaccine production. PMID:21835017

2011-01-01

163

Monitoring veterinary vaccines for contaminating viruses.  

PubMed

The detection of extraneous agents (EA) has always been critical for assessing the safety associated with vaccines. Vaccines and other biological medicines are derived from living substrates. This poses particular problems with regard to assuring their efficacy and safety due to the inherent variability of starting materials, the production processes, and the complex nature of the products themselves. For viral vaccines and other biological medicines, the key to effective quality control is rigorous testing and validation applied to the seed lots and also to the final batches. The quality assurance requirements for marketing products in Europe are given in the European Pharmacopoeia (EP). With the advent of molecular biotechnology, there are increasing uses of molecular methods for the characterization and quality control of vaccines. PCR for extraneous agent testing for live and inactivated poultry vaccines has been recognized to be a valid alternative testing method and is now being used extensively as a diagnostic tool in assuring the freedom from EAs. A number of generic PCR assays for product testing have been developed and validated. The current status and issues of the application of nucleic acid testing (NAT) to the standardization and control of vaccines will be reviewed. PMID:17058507

Ottiger, H P

2006-01-01

164

9 CFR 106.1 - Biological products; exemption.  

Code of Federal Regulations, 2011 CFR

...ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL...PROGRAMS OR UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1...or under the supervision or control of the Department in the prevention, control or eradication of...

2011-01-01

165

9 CFR 106.1 - Biological products; exemption.  

Code of Federal Regulations, 2014 CFR

...ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL...PROGRAMS OR UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1...or under the supervision or control of the Department in the prevention, control or eradication of...

2014-01-01

166

9 CFR 106.1 - Biological products; exemption.  

Code of Federal Regulations, 2012 CFR

...ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL...PROGRAMS OR UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1...or under the supervision or control of the Department in the prevention, control or eradication of...

2012-01-01

167

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

Code of Federal Regulations, 2014 CFR

...2014-01-01 false Requirements for primary cells used for production of biologics. 113...Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products...

2014-01-01

168

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

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Requirements for primary cells used for production of biologics. 113...Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products...

2013-01-01

169

78 FR 58311 - Complex Issues in Developing Drug and Biological Products for Rare Diseases; Public Workshop...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Developing Drug and Biological Products for Rare Diseases; Public Workshop; Request for...Developing Drug and Biological Products for Rare Diseases.'' The purpose of the public...biological products (``drugs'') for rare diseases, including endpoint...

2013-09-23

170

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

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Requirements for primary cells used for production of biologics. 113...Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products...

2011-01-01

171

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

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Requirements for primary cells used for production of biologics. 113...Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products...

2010-01-01

172

BIOLOGICAL CONTROL OF PESTS IN LIVESTOCK PRODUCTION  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

173

Production of hantavirus Puumala nucleocapsid protein in Saccharomyces cerevisiae for vaccine and diagnostics.  

PubMed

The production of hantavirus Puumala nucleocapsid (N) protein for potential applications as a vaccine and for diagnostic purposes was investigated with Saccharomyces cerevisiae as a recombinant host. The N protein gene and the hexahistidine tagged N (h-N) protein gene were expressed intracellular from a 2-microm plasmid vectors under the control of a fused galactose inducible GAL10-PYK promoter. For monitoring the recombinant gene expression, a h-N and a GFP fusion protein was used. Different cultivation strategies and growth media compositions were tested in shake flasks and a 5 l bioreactor. When using defined YNB growth medium, we found the biomass yield to be unsatisfactorily low. Higher concentrated YNB medium, promoted cell growth but showed a pronounced inhibitory effect on heterologous gene expression. This phenomenon could not be attributed to plasmid losses, as we could demonstrate high stability of the vector under the applied cultivation conditions. Supplementation of YNB medium with extracts of plant origin resulted in increased biomass yields with concomitant high expression levels of the recombinant gene. The modified medium was used for fed-batch cultivations where basic metabolic features as well as growth parameters were determined in addition to recombinant gene expression. The maximal volumetric yield of N protein was 316 mg l(-1), the respective yield of h-N protein was 284 mg l(-1). Our study provides a basis for large-scale production of hantavirus vaccines, which satisfies economic efficiency as well as biosafety regulations for human applications. PMID:16513199

Antoniukas, L; Grammel, H; Reichl, U

2006-07-13

174

Distributed modeling of human influenza A virus-host cell interactions during vaccine production.  

PubMed

This contribution is concerned with population balance modeling of virus-host cell interactions during vaccine production. Replication of human influenza A virus in cultures of adherent Madin-Darby canine kidney (MDCK) cells is considered as a model system. The progress of infection can be characterized by the intracellular amount of viral nucleoprotein (NP) which is measured via flow cytometry. This allows the differentiation of the host cell population and gives rise to a distributed modeling approach. For this purpose a degree of fluorescence is introduced as an internal coordinate which is linearly linked to the intracellular amount of NP. Experimental results for different human influenza A subtypes reveal characteristic dynamic phenomena of the cell distribution like transient multimodality and reversal of propagation direction. The presented population balance model provides a reasonable explanation for these dynamic phenomena by the explicit consideration of different states of infection of individual cells. Kinetic parameters are determined from experimental data. To translate the emerging infinite dimensional parameter estimation problem to a finite dimension the parameters are assumed to depend linearly on the internal coordinate. As a result, the model is able to reproduce all characteristic dynamic phenomena of the considered process for the two examined virus strains and allows deeper insight into the underlying kinetic processes. Thus, the model is an important contribution to the understanding of the intracellular virus replication and virus spreading in cell cultures and can serve as a stepping stone for optimization in vaccine production. PMID:23475474

Müller, Thomas; Dürr, Robert; Isken, Britta; Schulze-Horsel, Josef; Reichl, Udo; Kienle, Achim

2013-08-01

175

Gastrointestinal comorbidity, autistic regression and Measles-containing vaccines: positive re-challenge and biological gradient  

Microsoft Academic Search

Background: A temporal association between exposure to measles-containing vaccine (MCV) and autistic-like developmental regression in a sub- set of children with enterocolitis has been reported. Measles virus (MV) was detected in ileal biopsies from these children at higher prevalence than in developmentally normal pediatric controls. This study tested the hypothesis of a dose-response effect of MCV exposure on intestinal pathology,

Andrew J. Wakefield; Carol Stott

176

Hepatitis B Vaccine  

MedlinePLUS

Engerix-B® ... 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.In ...

177

Tetanus, Diphtheria (Td) Vaccine  

MedlinePLUS

Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... What is Td vaccine?Td vaccine can protect adolescents and adults from tetanus ... be given earlier after a severe and dirty wound or burn.Your doctor can ...

178

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

NASA Astrophysics Data System (ADS)

Key Words: Ultraviolet radiation,Standard Erythema Dose(SED), Minimal Erythema Dose(MED), Sun Burns, Solar Dermatitis, Sun Burned Disease, DNA Damage,Cell Damage, Antiradiation UV Vaccine, Immune-Prophylaxis of Sun Burned Diseases, Immune-Prophylaxis of Sun Burns, Immune-Therapy of Sun-Burned Disease and Sun Burns,Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), Toxic Epidermal Necrolysis(TEN). Introduction: High doses of UV generated by solar source and artificial sources create an exposure of mammals and other species which can lead to ultraviolet(UV)radiation- associated disease (including erythema, epilation, keratitis, etc.). UV radiation belongs to the non-ionizing part of the electromagnetic spectrum and ranges between 100 nm and 400 nm with 100 nm having been chosen arbitrarily as the boundary between non-ionizing and ionizing radiation, however EMR is a spectrum and UV can produce molecular ionization. UV radiation is conventionally categorized into 3 areas: UV-A (>315-400 nm),UV-B (>280-315 nm)and UV-C (>100-280 nm) [IARC,Working Group Reports,2005] An important consequence of stratospheric ozone depletion is the increased transmission of solar ultraviolet (UV)radiation to the Earth's lower atmosphere and surface. Stratospheric ozone levels have been falling, in certain areas, for the past several decades, so current surface ultraviolet-B (UV-B) radiation levels are thought to be close to their modern day maximum. [S.Madronich et al.1998] Overexposure of ultraviolet radiation a major cause of skin cancer including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) { collectively referred to as “non-melanoma" skin cancer (NMSC) and melanoma as well, with skin cancers being the most common cancer in North America. [Armstrong et al. 1993, Gallagher et al. 2005] Methods and Experimental Design: Our experiments and testing of a novel UV “Antiradiation Vaccine” have employed a wide variety of laboratory animals which include : Chinchilla rabbits, 11-12 months old, live weight 3.5-3.7 (n=11), Balb mice, 2-3 months old, live weight 20-22 g (n=33), Wistar rats, 3-4 months old, live weight 180-220 g(n=33). The studies were approved by the Animal Care and Use Committee for ethical animal research equivalent, at each institution. Seven rabbits, ten mice, eleven Wistar rats were vaccinated with a UV antiradiation vaccine. A second group of animals was used as biological control which received vaccine but no UV Radiation and a third group of animals was used as control without any interventions. Before and after UV Radiation, Vaccination with the UV antiradiation vaccine were provided 17 days prior to UV exposure. The animals were irradiated by a DRT-1 UV generator lamp. The dose of irradiation for laboratory, experimental animals was 10-12 * Standard Erythema Dose (SED) at L=283,7 Laboratory animals were placed in to the box with ventilation. Results: Ultraviolet irradiation of the skin was performed with high doses and causes an inflammation or erythema in all experimental animals. However the grade of skin damage and inflammation was significantly different between animals protected by vaccination and non-protected, non-vaccinated animals. Animals UV-irradiated, but who did not receive the antiradiation vaccine suffered from extensive UV skin burns of second or third degree (grade 2-3). However, animals protected with the UV antiradiation vaccine demonstrated much mild forms of skin cellular injury - mainly erythema, first degree skin burns and a few small patches with second degree skin burns (grade 1-2). Discussion: The severity of skin damage depended on area of exposed skin, time and dose of UV irradiation. Skin injury could be divided into 4 major grades: 1. Faint erythema with dry desquamation. 2. Moderate to severe erythema. 3. Severe erythema with blistering, moist desquamation. 4. Toxic epidermal necrolysis. Mild doses of UV radiation and ionizing radiation can induce cell death by apoptosis and moderate and high doses of UV and ionizing radiation induce cell death by necro

Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

179

The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) Study: Description of Methods of an Interventional Study Designed to Explore Complex Biologic Problems.  

PubMed

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

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

2015-04-01

180

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

Federal Register 2010, 2011, 2012, 2013, 2014

...document, the Commissioner of Food and Drugs (Commissioner...Management (HFA-305), Food and Drug Administration, 5630...Simplex Virus,'' Department of Microbiology, School of Medicine, Kyushu...Activity,'' Department of Microbiology, School of Medicine,...

2010-12-06

181

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

182

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

183

Minimization of excess sludge production for biological wastewater treatment  

Microsoft Academic Search

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

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

2003-01-01

184

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

185

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

186

Rotavirus vaccines.  

PubMed

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

Barnes, G

1998-01-01

187

Recombinant plants provide a new approach to the production of bacterial polysaccharide for vaccines.  

PubMed

Bacterial polysaccharides have numerous clinical or industrial uses. Recombinant plants could offer the possibility of producing bacterial polysaccharides on a large scale and free of contaminating bacterial toxins and antigens. We investigated the feasibility of this proposal by cloning and expressing the gene for the type 3 synthase (cps3S) of Streptococcus pneumoniae in Nicotinia tabacum, using the pCambia2301 vector and Agrobacterium tumefaciens-mediated gene transfer. In planta the recombinant synthase polymerised plant-derived UDP-glucose and UDP-glucuronic acid to form type 3 polysaccharide. Expression of the cps3S gene was detected by RT-PCR and production of the pneumococcal polysaccharide was detected in tobacco leaf extracts by double immunodiffusion, Western blotting and high-voltage paper electrophoresis. Because it is used a component of anti-pneumococcal vaccines, the immunogenicity of the plant-derived type 3 polysaccharide was tested. Mice immunised with extracts from recombinant plants were protected from challenge with a lethal dose of pneumococci in a model of pneumonia and the immunised mice had significantly elevated levels of serum anti-pneumococcal polysaccharide antibodies. This study provides the proof of the principle that bacterial polysaccharide can be successfully synthesised in plants and that these recombinant polysaccharides could be used as vaccines to protect against life-threatening infections. PMID:24498433

Smith, Claire M; Fry, Stephen C; Gough, Kevin C; Patel, Alexandra J F; Glenn, Sarah; Goldrick, Marie; Roberts, Ian S; Whitelam, Garry C; Andrew, Peter W

2014-01-01

188

Recombinant Plants Provide a New Approach to the Production of Bacterial Polysaccharide for Vaccines  

PubMed Central

Bacterial polysaccharides have numerous clinical or industrial uses. Recombinant plants could offer the possibility of producing bacterial polysaccharides on a large scale and free of contaminating bacterial toxins and antigens. We investigated the feasibility of this proposal by cloning and expressing the gene for the type 3 synthase (cps3S) of Streptococcus pneumoniae in Nicotinia tabacum, using the pCambia2301 vector and Agrobacterium tumefaciens-mediated gene transfer. In planta the recombinant synthase polymerised plant-derived UDP-glucose and UDP-glucuronic acid to form type 3 polysaccharide. Expression of the cps3S gene was detected by RT-PCR and production of the pneumococcal polysaccharide was detected in tobacco leaf extracts by double immunodiffusion, Western blotting and high-voltage paper electrophoresis. Because it is used a component of anti-pneumococcal vaccines, the immunogenicity of the plant-derived type 3 polysaccharide was tested. Mice immunised with extracts from recombinant plants were protected from challenge with a lethal dose of pneumococci in a model of pneumonia and the immunised mice had significantly elevated levels of serum anti-pneumococcal polysaccharide antibodies. This study provides the proof of the principle that bacterial polysaccharide can be successfully synthesised in plants and that these recombinant polysaccharides could be used as vaccines to protect against life-threatening infections. PMID:24498433

Smith, Claire M.; Fry, Stephen C.; Gough, Kevin C.; Patel, Alexandra J. F.; Glenn, Sarah; Goldrick, Marie; Roberts, Ian S.; Andrew, Peter W.

2014-01-01

189

Influenza Vaccines Have a Short but Illustrious History of Dedicated Science Enabling the Rapid Global Production of A\\/Swine (H1N1) Vaccine in the Current Pandemic  

Microsoft Academic Search

\\u000a Vaccines for the swine flu pandemic of 2009 have been produced in an exquisitely short time frame. This speed of production\\u000a comes because of 50 years of hard work by virologists worldwide in pharma groups, research laboratories, and government licensing\\u000a units. The present chapter presents the background framework of influenza vaccine production and its evolution over 50 years.\\u000a Isolation of

John Oxford; Anthony Gilbert; Robert Lambkin-Williams

190

Biological Hydrogen Production Using a Membrane Bioreactor  

E-print Network

was removed, producing 2200 mg/L of cells and 500 mL/h of biogas. When operated in MBR mode, the solids. This SRT increased the overall glucose utilization (98%), the biogas production rate (640 m,800 F 600 mg/L) both increased. However, the biogas produc- tion decreased (310 F 40 m

191

The androgen receptor: a biologically relevant vaccine target for the treatment of prostate cancer  

PubMed Central

The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. However, while it has long been the primary molecular target of metastatic prostate cancer therapies, it has not been explored as an immunotherapeutic target. In particular, the AR ligand-binding domain (LBD) is a potentially attractive target, as it has an identical sequence among humans as well as among multiple species, providing a logical candidate for preclinical evaluation. In this report, we evaluated the immune and anti-tumor efficacy of a DNA vaccine targeting the AR LBD (pTVG-AR) in relevant rodent preclinical models. We found immunization of HHDII-DR1 mice, which express human HLA-A2 and HLA-DR1, with pTVG-AR augmented AR LBD HLA-A2-restricted peptide-specific, cytotoxic immune responses in vivo that could lyse human prostate cancer cells. Using an HLA-A2-expressing autochthonous model of prostate cancer, immunization with pTVG-AR augmented HLA-A2-restricted immune responses that could lyse syngeneic prostate tumor cells and led to a decrease in tumor burden and an increase in overall survival of tumor-bearing animals. Finally, immunization decreased prostate tumor growth in Copenhagen rats that was associated with a Th1-type immune response. These data show that the AR is as a prostate cancer immunological target antigen and that a DNA vaccine targeting the AR LBD is an attractive candidate for clinical evaluation. PMID:23108626

Olson, Brian M.; Johnson, Laura E.

2012-01-01

192

Developmental Biology of Sporozoite-Host Interactions in Plasmodium falciparum Malaria: Implications for Vaccine Design  

PubMed Central

The Plasmodium falciparum sporozoite infects different types of cells in a mosquito's salivary glands and human epithelial and Kuppfer cells and hepatocytes. These become differentiated later on, transforming themselves into the invasive red blood cell form, the merozoite. The ability of sporozoites to interact with different types of cells requires a wide variety of mechanisms allowing them to survive in both hosts: mobility, receptor-ligand interactions with different cellular receptors, and transformation and development into other invasive parasite forms, which are vitally important for parasite survival. Sporozoite complexity is reflected in the large quantity of proteins that can be expressed. Some of them have been extensively studied, such as CSP, TRAP, STARP, LSA-1, LSA-3, SALSA, SPECT1, SPECT2, MAEBL, and SPATR, due to their importance in infection and their potential use as vaccines. Our work has been focused on the search for the molecular mechanisms of parasite-host cellular receptor-ligand interactions by identifying amino acid sequences and the critical binding residues from these proteins relevant to parasite invasion. Once such sequences have been identified, it will be possible to modify them to induce a strong immune response against P. falciparum in the experimental Aotus monkey model. This all leads towards developing multistage, multicomponent, subunit-based vaccines that will be effective in eradicating or controlling malaria caused by P. falciparum. PMID:17041140

Garcia, Javier E.; Puentes, Alvaro; Patarroyo, Manuel E.

2006-01-01

193

[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

194

Cytokine production and dysregulation in HIV pathogenesis: Lessons for development of therapeutics and vaccines  

PubMed Central

Numerous studies have characterized the cytokine modulation observed in human immunodeficiency virus (HIV) infected individuals, from initial infection through chronic disease. Progressive and non-progressive HIV infection models show the cytokine milieu differs in terms of production and responsiveness in these two groups, suggesting an understanding of the role cytokines play during infection is necessary for directing the immune response toward viral control. This review will cover cytokine induction and dysfunction during HIV pathogenesis, with a focus on the interplay between cytokines and transcription factors, T cell activation, and exhaustion. We highlight cytokines that have either vaccine adjuvant or therapeutic potential and discuss the need to identify key factors required for prevention of progression, clearance of infection, or protection from acquisition. PMID:22743036

Reuter, Morgan A.; Pombo, Carolina; Betts, Michael R.

2012-01-01

195

Biological production of liquid fuels from biomass  

SciTech Connect

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

none,

1982-01-01

196

Biological treatment of shrimp production wastewater  

Microsoft Academic Search

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

Raj Boopathy

2009-01-01

197

L OW IGG FBS: APPLICATIONS TO MONOCLONAL ANTIBODY AND VACCINE PRODUCTION  

Microsoft Academic Search

etal bovine serum (FBS) has long been used as a supplement for tissue culture media, supplying growth factors and attachment factors essential for the culturing and proliferation of cells in vitro. The production of biological agents (i.e., mono- clonal antibodies (MAbs)) from cell culture has highlighted some benefits and drawbacks in using FBS. Hybridomas that cannot be cultured under serum-free

R. J. Docherty; A. O. Hamilton; N. Pattison; G. Mounsey; R. Foster; P. Hodgson; G. Benny

198

Neurotrophic Natural Products: Chemistry and Biology  

PubMed Central

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

Xu, Jing; Lacoske, Michelle H.

2014-01-01

199

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

Microsoft Academic Search

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

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

2008-01-01

200

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. PMID:22688446

Singh, Shanteri; Phillips, George N.

2012-01-01

201

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.

202

DNA vaccines: ready for prime time?  

PubMed Central

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

Kutzler, Michele A.; Weiner, David B.

2015-01-01

203

The Interstellar Production of Biologically Important Organics  

NASA Technical Reports Server (NTRS)

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

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

2000-01-01

204

Synthetic biology of avermectin for production improvement and structure diversification.  

PubMed

Natural products are still key sources of current clinical drugs and innovative therapeutic agents. Since wild-type microorganisms only produce natural products in very small quantities, yields of production strains need to be improved by breaking down the precise genetic and biochemical circuitry. Herein, we use avermectins as an example of production improvement and chemical structure diversification by synthetic biology. Avermectins are macrocyclic lactones produced by Streptomyces avermitilis and are well known and widely used for antiparasitic therapy. Given the importance of this molecule and its derivatives, many efforts and strategies were employed to improve avermectin production and generate new active analogues. This review describes the current status of synthetic strategies successfully applied for developing natural-product-producing strains and discusses future prospects for the application of enhanced avermectin production. PMID:24478271

Zhuo, Ying; Zhang, Tao; Wang, Qi; Cruz-Morales, Pablo; Zhang, Buchang; Liu, Mei; Barona-Gómez, Francisco; Zhang, Lixin

2014-03-01

205

Irradiation of advanced health care products - Tissues and biologics  

NASA Astrophysics Data System (ADS)

Radiation sterilization of tissues and biologics has become more common in recent years. As a result it has become critical to understand how to adapt the typical test methods and validation approaches to a tissue or biological product scenario. Also data evaluation sometimes becomes more critical than with traditional medical devices because for many tissues and biologics a low radiation dose is required. It is the intent behind this paper to provide information on adapting bioburden tests used in radiation validations such that the data can be most effectively used on tissues and biologics. In addition challenges with data evaluation are discussed, particularly the use of less-than values for bioburden results in radiation validation studies.

Winters, Martell

2014-12-01

206

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

PubMed Central

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

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

2014-01-01

207

Flow cytometric monitoring of influenza A virus infection in MDCK cells during vaccine production  

PubMed Central

Background In cell culture-based influenza vaccine production the monitoring of virus titres and cell physiology during infection is of great importance for process characterisation and optimisation. While conventional virus quantification methods give only virus titres in the culture broth, data obtained by fluorescence labelling of intracellular virus proteins provide additional information on infection dynamics. Flow cytometry represents a valuable tool to investigate the influences of cultivation conditions and process variations on virus replication and virus yields. Results In this study, fluorescein-labelled monoclonal antibodies against influenza A virus matrix protein 1 and nucleoprotein were used for monitoring the infection status of adherent Madin-Darby canine kidney cells from bioreactor samples. Monoclonal antibody binding was shown for influenza A virus strains of different subtypes (H1N1, H1N2, H3N8) and host specificity (human, equine, swine). At high multiplicity of infection in a bioreactor, the onset of viral protein accumulation in adherent cells on microcarriers was detected at about 2 to 4 h post infection by flow cytometry. In contrast, a significant increase in titre by hemagglutination assay was detected at the earliest 4 to 6 h post infection. Conclusion It is shown that flow cytometry is a sensitive and robust method for the monitoring of viral infection in fixed cells from bioreactor samples. Therefore, it is a valuable addition to other detection methods of influenza virus infection such as immunotitration and RNA hybridisation. Thousands of individual cells are measured per sample. Thus, the presented method is believed to be quite independent of the concentration of infected cells (multiplicity of infection and total cell concentration) in bioreactors. This allows to perform detailed studies on factors relevant for optimization of virus yields in cell cultures. The method could also be used for process characterisation and investigations concerning reproducibility in vaccine manufacturing. PMID:18447925

Schulze-Horsel, Josef; Genzel, Yvonne; Reichl, Udo

2008-01-01

208

Evaluation of the Immunogenicity and Biological Activity of the Citrobacter freundii Vi-CRM197 Conjugate as a Vaccine for Salmonella enterica Serovar Typhi? †  

PubMed Central

Typhoid fever remains a major health problem in developing countries. Young children are at high risk, and a vaccine effective for this age group is urgently needed. Purified capsular polysaccharide from Salmonella enterica serovar Typhi (Vi) is licensed as a vaccine, providing 50 to 70% protection in individuals older than 5 years. However, this vaccine is ineffective in infants. Vi conjugated to a carrier protein (i.e., an exoprotein A mutant from Pseudomonas aeruginosa [rEPA]) is highly immunogenic, provides long-term protection, and shows more than 90% protective efficacy in children 2 to 5 years old. Here, we describe an alternative glycoconjugate vaccine for S. Typhi, Vi-CRM197, where Vi was obtained from Citrobacter freundii WR7011 and CRM197, the mutant diphtheria toxin protein, was used as the carrier. We investigated the optimization of growth conditions for Vi production from C. freundii WR7011 and the immunogenicity of Vi-CRM197 conjugates in mice. The optimal saccharide/protein ratio of the glycoconjugates was identified for the best antibody production. We also demonstrated the ability of this new vaccine to protect mice against challenge with Vi-positive Salmonella enterica serovar Typhimurium. PMID:21248155

Rondini, Simona; Micoli, Francesca; Lanzilao, Luisa; Hale, Christine; Saul, Allan J.; Martin, Laura B.

2011-01-01

209

Vaccines against poverty  

PubMed Central

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

MacLennan, Calman A.; Saul, Allan

2014-01-01

210

Vaccines against poverty.  

PubMed

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

MacLennan, Calman A; Saul, Allan

2014-08-26

211

Natural products with health benefits from marine biological resources  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

212

Hydrogen production by biological processes: a survey of literature  

Microsoft Academic Search

Hydrogen is the fuel of the future mainly due to its high conversion efficiency, recyclability and nonpolluting nature. Biological hydrogen production processes are found to be more environment friendly and less energy intensive as compared to thermochemical and electrochemical processes. They are mostly controlled by either photosynthetic or fermentative organisms. Till today, more emphasis has been given on the former

Debabrata Das; T. Nejat Veziro?lu

2001-01-01

213

Physical Transport of Nutrients and the Maintenance of Biological Production  

E-print Network

nutrients within the water column through transport and mixing. The combined role of biogeochemicalChapter 2 Physical Transport of Nutrients and the Maintenance of Biological Production Richard G. Williams · Michael J. Follows 2.1 Introduction The oceanic distributions of nutrients and patterns

Follows, Mick

214

Biology and management of psocids infesting stored products  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

215

Foot and mouth disease virus vaccines.  

PubMed

Foot and mouth disease (FMD) is a highly infectious and economically devastating disease of livestock. Although vaccines, available since the early 1900s, have been instrumental in eradicating FMD from parts of the world, the disease still affects millions of animals around the globe and remains the main sanitary barrier to the commerce of animals and animal products. Currently available inactivated antigen vaccines applied intramuscularly to individual animals, confer serotype and subtype specific protection in 1-2 weeks but fail to induce long-term protective immunity. Among the limitations of this vaccine are potential virus escape from the production facility, short shelf life of formulated product, short duration of immunity and requirement of dozens of antigens to address viral antigenic diversity. Here we review novel vaccine approaches that address some of these limitations. Basic research and the combination of reliable animal inoculation models, reverse genetics and computational biology tools will allow the rational design of safe and effective FMD vaccines. These vaccines should address not only the needs of FMD-free countries but also allow the progressive global control and eradication of this devastating disease. PMID:19837296

Rodriguez, Luis L; Grubman, Marvin J

2009-11-01

216

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

217

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. PMID:23577007

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

2013-01-01

218

Immune responses of humans to a human diploid cell strain of rabies virus vaccine: lymphocyte transformation, production of virus-neutralizing antibody, and induction of interferon.  

PubMed

Lymphocyte transformation, production of neutralizing antibody, and interferon activity of 20 healthy volunteers in response to a human diploid cell strain (HDCS) of rabies virus vaccine were studied. Ten vaccines received 1.0 ml of HDCS vaccine on days 0, 3, 7, and 14, and five of these volunteers received, in addition, 20 international units of human rabies immune globulin/kg of body weight on day 0. All 10 volunteers developed high titers of neutralizing antibody, and eight of the 10 had lymphocytes that were immunologically stimulated by HDCS rabies virus antigen. The interferon responses of eight vaccines to 1.0 ml of HDCS vaccine given intramuscularly on days 0 and 28 and of two vaccines to 1.0 ml of vaccine given intradermally in eight body sites on the same days were measured; low levels of interferon-like activity were found in eight of nine volunteers after the first vaccination, and no activity was found upon revaccination. The high titers of neutralizing antibody that developed did not correlate with lymphocyte stimulation or interferon-like activity, but it is true that all 20 volunteers did develop high titers of neutralizing antibody after 1.0 ml of HDCS vaccine was given intradermally. PMID:479638

Nicholson, K G; Cole, P J; Turner, G S; Harrison, P

1979-08-01

219

Edible vaccines  

Microsoft Academic Search

The ultimate vaccine is an oral vaccine which given once protects against a multitude of diseases. Furthermore this ultimate vaccine needs to be very stable and inexpensive to produce. Probably this latter condition can be met only if the vaccines are produced in plants. Such vaccines are called ‘edible vaccines’. Edible vaccines can be produced in plants in many ways.

R. H. Meloen; W. D. O. Hamilton; J. I. Casal; K. Dalsgaard; J. P. M. Langeveld

1998-01-01

220

Application of genomics and proteomics for identification of bacterial gene products as potential vaccine candidates  

Microsoft Academic Search

The ability of bioinformatics to characterize genomic sequences from pathogenic bacteria for prediction of genes that may encode vaccine candidates, e.g. surface localized proteins, has been evaluated. By applying appropriate tools for genomic mining to the published sequence of Haemophilus influenzae Rd genome, it was possible to identify a putative vaccine candidate, the outer membrane lipoprotein, P6. Proteomics complements genomics

Deb N Chakravarti; Michael J Fiske; Leah D Fletcher; Robert J Zagursky

2000-01-01

221

Production and characterisation of alginate microparticles incorporating Aeromonas hydrophila designed for fish oral vaccination  

Microsoft Academic Search

Oral vaccination is a relevant alternative for fish immunisation in intensive culture. However, its effectiveness is limited by possible vaccine degradation in the fish digestive system. The purpose of this work was to obtain stable biocompatible alginate microparticles entrapping inactive Aeromonas hydrophila cells for fish oral immunisation. The particles were prepared through an emulsion-based methodology, employing different vegetable oils containing

A. P. Rodrigues; Daniela Hirsch; H. C. P. Figueiredo; P. V. R. Logato; Â. M. Moraes

2006-01-01

222

To Vaccinate, or Not to Vaccinate That is the Question  

NSDL National Science Digital Library

The case was prompted by a newspaper story about a couple who refused on religious grounds to have their son vaccinated even though vaccination is a requirement for admission to the public schools. It explores the issues surrounding the necessity and consequences of vaccination.  The case is suitable for both non-majors and allied health biology courses.

Caren D. Shapiro

2001-01-01

223

Oral vaccination of dogs with recombinant rabies virus vaccines  

Microsoft Academic Search

Oral rabies virus (RV) vaccines are used to immunize a diversity of mammalian carnivores, but no single biological is effective for all major species. Recently, advances in reverse genetics have allowed the design of recombinant RV for consideration as new vaccines. The objective of this experiment was to examine the safety, immunogenicity and efficacy of recombinant RV vaccines administered to

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

2005-01-01

224

9 CFR 113.65 - Brucella Abortus Vaccine.  

Code of Federal Regulations, 2010 CFR

...ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.65 Brucella Abortus Vaccine. Brucella Abortus Vaccine shall be prepared as a desiccated live culture bacterial vaccine from smooth colonial forms of the...

2010-01-01

225

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

SciTech Connect

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

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

2012-05-18

226

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

227

Original article Vaccination against swine enzootic pneumonia  

E-print Network

Original article Vaccination against swine enzootic pneumonia in field conditions: effect of vaccination against swine enzootic pneumonia in different production systems (closed or one-site, and open of macroscopic diagnosis in field conditions. pig / Mycoplasma hyopneumoniae / enzootic pneumonia / vaccine

Paris-Sud XI, Université de

228

Plant-based vaccines for animal health  

Microsoft Academic Search

Summary Plant-based vaccines are recombinant protein subunit vaccines. Ideally, the choice of plant species used to produce the selected antigen should allow for oral delivery in the form of an edible vaccine. These vaccines are well suited to combat diseases where there is a clear antigen candidate, and where the costs of production or delivery for any current vaccine are

S. J. Streatfield

2005-01-01

229

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

PubMed

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

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

2014-09-01

230

Economics of animal vaccination.  

PubMed

This paper describes the steps that might be used in assessing the economic justification for using vaccination to control animal disease, and the way that vaccination is financed and administered. It describes decisions that have been taken with respect to preserving international trade, and issues related to protection of livelihoods. Regardless of the motivation for vaccination, its costs can usually be shared between the public and private sectors. Cost-effective vaccination requires methods of delivery to be adapted to livestock production systems. The paper concludes by suggesting questions around the use of vaccination that would merit further economic analysis. PMID:17892154

McLeod, A; Rushton, J

2007-08-01

231

Role of Pharmacovigilance on Vaccines Control*  

PubMed Central

The pharmacovigilance of vaccines is defined as the science and activities relating to the detection, assessment, understanding, prevention and communication of adverse events of immunization, or any other vaccine, or issues related with immunization. The strengthening of pharmacovigilance is very important in every country because it helps professional health care workers to avoid the problems with immunization, protect the health of people from adverse events during immunization. The success of the immunization system is reducing morbidity and mortality related to the vaccine. The vaccines are biological products used to prevent infectious diseases, but sometimes the vaccines can cause some AEFI (Adverse Events Following Immunization). The detection of adverse events following correct immunization is one very important step for prevention of problems in the immunization system. The vaccines are injected into an infant body on the day of their birth and the safety of these products is vital. In Albania, the Pharmacovigilance department is established as the structure of the National Center of Drug Control. The strengthening of pharmacovigilance in Albania and other countries is necessary, because this will help to identify the risk and the risk factors, and to avoid or minimize the harms. PMID:25648188

Kuçuku, Merita

2012-01-01

232

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

PubMed Central

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

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

2014-01-01

233

FDA: CVaccines, Blood & Biologics  

NSDL National Science Digital Library

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

234

Nanotoxoid Vaccines.  

PubMed

To improve innate defense against diseases, vaccine formulations are routinely administered to mount immune responses against disease-causing organisms or their associated toxins. These formulations are typically prepared with weakened forms of microbes, their surface proteins, or their virulence factors, which can train the immune system to recognize and neutralize similar infectious threats in later exposures. Owing to many unique properties of nanoparticles in enhancing vaccine potency, nanoscale carriers are drawing increasing interest as a platform for developing safer and more effective vaccine formulations. Notably, a nanoparticle-based strategy was recently demonstrated to safely deliver intact, non-denatured protein toxins to mount a potent anti-toxin immune response. A biomimetic nanoparticle cloaked in biological membranes was used to sequester membrane-active toxins. Upon interaction with the nanoparticles, the toxins become retrained and lose their toxicity as they are precluded from interacting with cellular targets. The resulting particle/toxin complex adopts a nanoparticulate morphology that facilitates the toxins' intracellular delivery. This sequestration approach has immense immunological implications owing to its ability in enabling structurally preserved toxins for immune processing. This technique offers opportunities in novel toxoid vaccine designs that promise more effective anti-toxin immune responses and contrasts the existing paradigm in toxoid preparation, in which toxins are antigenically altered to ensure virulence removal. The potent nanotoxoid formulations provide a viable anti-virulence measure in combating microbial infections that involve membrane-damaging toxins, including methicillin-resistant Staphylococcus aureus (MRSA) and Group A streptococcal infections. PMID:25285152

Hu, Che-Ming J; Zhang, Liangfang

2014-08-01

235

HPV vaccine  

MedlinePLUS

Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... men Two vaccines called HPV2 (Cervarix) and HPV4 (Gardasil) are approved: Both vaccines protect against the two ...

236

Typhoid Vaccine  

MedlinePLUS

... around the world and kills about 200,000. Typhoid vaccine can prevent typhoid. ... Who should get typhoid vaccine and when?Routine typhoid vaccination is not recommended in the United States, but typhoid vaccine is recommended for: Travelers ...

237

Unraveling the Convoluted Biological Roles of Type I Interferons in Infection and Immunity: A Way Forward for Therapeutics and Vaccine Design  

PubMed Central

It has been well-established that type I interferons (IFN-Is) have pleiotropic effects and play an early central role in the control of many acute viral infections. However, their pleiotropic effects are not always beneficial to the host and in fact several reports suggest that the induction of IFN-Is exacerbate disease outcomes against some bacterial and chronic viral infections. In this brief review, we probe into this mystery and try to develop answers based on past and recent studies evaluating the roles of IFN-Is in infection and immunity as this is vital for developing effective IFN-Is based therapeutics and vaccines. We also discuss the biological roles of an emerging IFN-I, namely IFN-?, and discuss its potential use as a mucosal therapeutic and/or vaccine adjuvant. Overall, we anticipate the discussions generated in this review will provide new insights for better exploiting the biological functions of IFN-Is in developing efficacious therapeutics and vaccines in the future. PMID:25221557

Wijesundara, Danushka Kumara; Xi, Yang; Ranasinghe, Charani

2014-01-01

238

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

Federal Register 2010, 2011, 2012, 2013, 2014

...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

239

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

PubMed Central

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

Lexchin, Joel; Arya, Neil; Singh, Sonal

2010-01-01

240

78 FR 32668 - Draft Guidance for Industry: Changes to an Approved Application: Biological Products: Human Blood...  

Federal Register 2010, 2011, 2012, 2013, 2014

...an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture...an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or...

2013-05-31

241

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. PMID:21984246

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

2011-01-01

242

Recombinant Influenza Vaccines  

PubMed Central

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

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

2012-01-01

243

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

244

Valuing vaccination.  

PubMed

Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

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

2014-08-26

245

Valuing vaccination  

PubMed Central

Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

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

2014-01-01

246

Towards universal influenza vaccines?  

PubMed Central

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

Osterhaus, Ab; Fouchier, Ron; Rimmelzwaan, Guus

2011-01-01

247

Functional characterization of Edwardsiella tarda twin-arginine translocation system and its potential use as biological containment in live attenuated vaccine of marine fish.  

PubMed

Bacterial twin-arginine translocation (Tat) system contributes to translocate folded proteins to the periplasm and plays pleiotropic roles in physiological fitness. Here, we showed that the fish pathogen Edwardsiella tarda Tat pathway was functional and was essential for H2S production and hemolytic activity. E. tarda Tat mutant was more susceptible to diverse stresses such as high temperature, SDS, ethanol, and high-salt conditions. However, E. tarda Tat mutant displayed marginal in vivo virulence attenuation in fish models. Comparative proteomics analysis using two-dimensional gel electrophoresis (2-DGE) and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry were performed to identify proteins undergoing changes in expression levels under high-salt conditons when the Tat pathway was mutilated. Of the 96 differently expressed proteins on the 2-DGE map, 15 proteins were successfully identified with a MASCOT score >45 (p?biological containment system for live attenuated vaccine (LAV) in marine fish vaccinology. To test this, we deleted the type III secretion system genes and cured endogenous plasmid pEIB202 to construct a LAV candidate in the context of Tat abrogation in E. tarda. The results indicated that the LAV candidate was highly attenuated when injected intraperitoneally and elicited significant protection against challenge of wild-type E. tarda in turbot while being rapidly eliminated in seawater. PMID:23053108

Wang, Yamin; Wang, Qiyao; Yang, Weizheng; Liu, Bing; Zhang, Yuanxing

2013-04-01

248

Regulatory harmonization--a vaccine industry perspective.  

PubMed

With growth and diversification of aquaculture has come the dissemination of diseases and the increased need to use control measures, both preventative and therapeutic. Preventative measures include good husbandry practices, adequate nutrition and the use of vaccines. Vaccines for aquaculture have generally fallen under the regulatory control of national veterinary medicinal or biological agencies and with that a diverse range of regulatory requirements for authorization and use. More so than any other food animal industry, aquaculture is an international industry with individual entities holding multinational ownership. This situation has created unique problems for the manufacturers of biologicals attempting to service the industry. In recent years, a concerted effort has been made to harmonize regulations to facilitate international trade of vaccines as well as vaccinated animal stocks and their processed food products within and among trading partners. Standardization of requirements for manufacture and testing would ensure national and international interests and consumers of pure, safe and effective products. As the path to harmonization has been slow and not without disagreements, the question remains: What will the standardized requirements be? The manufacturing philosophies of process control (Good Manufacturing Practice) and governmental final product testing for batch release can create a duplicity of effort on the part of the manufacturer that equates to higher economic costs and greater time constraints. The current lack of standardized quality control test methods often means conducting multiple tests to provide the same result. Although efforts are being made to recognize these differences, historical regulations today are based on injectable vaccines for warm-blooded animals. Administration of vaccine products to cold-blooded aquatic species by immersion, bath and oral routes, as well as by injection, creates interpretive problems for manufacturers and regulators alike. Industry encourages and awaits regulatory harmonization, standardization or equivalence. It also offers and would appreciate an active role in the final process. PMID:9270864

Goodrich, T D

1997-01-01

249

Vaccination and consumer perception of seafood quality.  

PubMed

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

Engelstad, M

2005-01-01

250

21 CFR 310.4 - Biologics; products subject to license control.  

Code of Federal Regulations, 2011 CFR

...Biologics; products subject to license control. 310.4 Section 310.4 Food...Biologics; products subject to license control. (a) If a drug has an approved...obtain marketing approval for radioactive biological products for human use, as defined...

2011-04-01

251

21 CFR 310.4 - Biologics; products subject to license control.  

Code of Federal Regulations, 2010 CFR

...Biologics; products subject to license control. 310.4 Section 310.4 Food...Biologics; products subject to license control. (a) If a drug has an approved...obtain marketing approval for radioactive biological products for human use, as defined...

2010-04-01

252

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

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Requirements for cell lines used for production of biologics...Requirements § 113.52 Requirements for cell lines used for production of biologics...or in a filed Outline of Production each cell line used to prepare a biological...

2010-01-01

253

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

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Requirements for cell lines used for production of biologics...Requirements § 113.52 Requirements for cell lines used for production of biologics...or in a filed Outline of Production each cell line used to prepare a biological...

2011-01-01

254

Cattle, sheep and pigs vaccinated against foot and mouth disease: does trade in these animals and their products present a risk of transmitting the disease?  

PubMed

The foot and mouth disease (FMD) status of a country or region has a profound bearing on access to export markets for live animals and animal products. In countries without FMD-free status, and in accordance with the international standards of the World Organisation for Animal Health (OIE), restrictions may be applied to trade in both vaccinated and unvaccinated animals and their products. Available information suggests that, provided there is compliance with essential criteria concerning vaccines, vaccination and other zoosanitary measures (especially quarantine and ante- and post-mortem inspection), the risk of spreading FMD through the importation of vaccinated cattle, sheep and pigs is extremely small. The risk from products derived from vaccinated animals is even smaller, provided that appropriate risk mitigation measures are applied. Knowledge of the zoosanitary status of the exporting country is critical for risk assessment, but can be difficult to verify. Although empirical evidence and practical experience strongly indicate low risk, it is not possible to assert that the risk is zero for vaccinated animals or their products. In the absence of key factual data, risk analysis is only practicable on a qualitative or semi-quantitative basis. However, a very low level of risk is both unavoidable and acceptable if such trade is to be conducted. PMID:21809764

Garland, A J M; de Clercq, K

2011-04-01

255

Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine  

MedlinePLUS

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

256

Vaccine hesitancy  

PubMed Central

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

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

2013-01-01

257

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. PMID:21772787

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

2010-01-01

258

Recombinant vaccines and the development of new vaccine strategies  

PubMed Central

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks. PMID:22948379

Nascimento, I.P.; Leite, L.C.C.

2012-01-01

259

Impact of Severe Weather Conditions on Biological Products  

MedlinePLUS

... business hours parties may call the FDA emergency operations line at 301-796-8240. These questions will be forwarded to the appropriate Center or office for advice. Vaccines Requiring Refrigeration or ...

260

Evaluation of three 'ready to formulate' oil adjuvants for foot-and-mouth disease vaccine production.  

PubMed

Foot-and-mouth disease virus (FMDV) type OR(2)/75, grown on BHK 21 clone 13 cell monolayers, was inactivated with formalin. The virus was clarified and was either concentrated with 8% polyethylene glycol 6000 (PEG) or used in its untreated form for the preparation of oil adjuvant vaccines. The oil adjuvants used in this study were Montanide ISA 206 (which renders a water-in-oil-in-water (w/o/w) type of emulsion), Montanide ISA 57 and Montanide ISA 50V (both of which render water-in-oil (w/o) type of emulsions). The vaccines were tested on guinea pigs and calves. The results indicated that vaccines emulsified using Montanide ISA 57 elicited the best protective immune response in the animals, followed by those emulsified with Montanide ISA 50V and Montanide ISA 206. It was also found that vaccines formulated with virus concentrated using 8% polyethylene glycol (PEG) were more immunogenic than the vaccines formulated with the untreated harvest virus. PMID:11137244

Iyer, A V; Ghosh, S; Singh, S N; Deshmukh, R A

2000-12-01

261

Identification of a new reovirus causing substantial losses in broiler production in France, despite routine vaccination of breeders.  

PubMed

Numerous cases of tenosynovitis appeared in France causing high morbidity in free-range and standard broilers. The main clinical findings were lameness, stunting and non-uniform bodyweights. Although the natural mortality was low, the economic losses due to birds that had to be removed from the flock prematurely, downgrading of carcases and lower average weights at slaughter were substantial. Postmortem examinations, bacteriological, virological and serological examination confirmed the aetiology of avian orthoreovirus (ARV)-induced tenosynovitis. The isolated ARVs were analysed serologically and genetically. Sequencing of ?C RT-PCR products and phylogenetic analysis revealed a new type of ARV. The virus was not neutralised in serum neutralisation test using monovalent sera from vaccinated chickens. Together with the flock data, epidemiology of these recent reovirus outbreaks in France was reconstructed. It is concluded that these reovirus isolates differ serologically and genetically from the well described reovirus isolates used in commercial vaccines which were not capable of preventing the disease. The outbreaks resulted in substantial losses in broilers from vaccinated breeders. PMID:23636701

Troxler, S; Rigomier, P; Bilic, I; Liebhart, D; Prokofieva, I; Robineau, B; Hess, M

2013-05-25

262

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

PubMed

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

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

2015-01-01

263

Systems biological approaches towards understanding cellulase production by Trichoderma reesei.  

PubMed

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

Kubicek, Christian P

2013-01-20

264

Current approaches to vaccine preparation  

PubMed Central

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

Liu, Jiang-Jian; Cepica, Arnost

1990-01-01

265

A quantitative analysis for the ADP-ribosylation activity of pertussis toxin: an enzymatic-HPLC coupled assay applicable to formulated whole cell and acellular pertussis vaccine products.  

PubMed

The majority of the biological effects of pertussis toxin (PT) are the result of a toxin-catalyzed transfer of an adenosine diphosphate-ribose (ADP-ribose) moiety from NAD(+)to the alpha-subunits of a subset of signal-transducing guanine-nucleotide-binding proteins (G-proteins). This generally leads to an uncoupling of the modified G-protein from the corresponding receptor and the loss of effector regulation. This assay is based on the PT S1 subunit enzymatic transfer of ADP-ribose from NAD to the cysteine moiety of a fluorescent tagged synthetic peptide homologous to the 20 amino acid residue carboxyl-terminal sequence of the alpha-subunit of the G(i3)protein. The tagged peptide and the ADP-ribosylated product were characterized by HPLC/MS and MS/MS for structure confirmation. Quantitation of this characterized ADP-ribosylated fluorescently tagged peptide was by HPLC fluorescence using Standard Addition methodology. The assay was linear over a five hr incubation period at 20 degrees C at PT concentrations between 0.0625 and 4.0 microg/ml and the sensitivity of the assay could be increased several fold by increasing the incubation time to 24 h. Purified S1 subunit of PT exhibited 68.1+/-10.1% of the activity of the intact toxin on a molar basis, whereas the pertussis toxin B oligomer, the genetically engineered toxoid, (PT-9K/129G), and several of the other components of the Bordetella pertussis organism possessed little (<0.6%) or no detectable ribosylation activity. Commonly used pertussis vaccine reference materials, US PV Lot #11, BRP PV 66/303, and BRP PV 88/522, were assayed by this method against Bordetella pertussis Toxin Standard 90/518 and demonstrated to contain, respectively, 0.323+/-0.007, 0.682+/-0.045, and 0.757+/-0.006 microg PT/ml (Mean+/-SEM) or in terms of microg/vial: 3.63, 4.09 and 4.54, respectively. A survey of several multivalent pertussis vaccine products formulated with both whole cell as well as acellular components indicated that products possessed a wide range of ribosylation activities. The pertussis toxin S1 subunit catalyzed ADP- ribosylation of the FAC-Galpha(i3)C20 peptide substrate and its subsequent quantitation by HPLC was demonstrated to be a sensitive and quantitative method for measuring intrinsic pertussis toxin activity. This methodology not only has the potential to be an alternative physicochemical method to replace existing bioassay methodology, but has the added advantage of being a universal method applicable to the assay of pertussis toxin in both whole cell and acellular vaccines as well as bulk and final formulated vaccine products. Acceptance of this method by regulatory agencies and industry as a credible alternative to existing methods would, however, require validation in an international collaborative study against the widely accepted bioassay methods. PMID:11580213

Cyr, T; Menzies, A J; Calver, J; Whitehouse, L W

2001-06-01

266

Adjuvants for allergy vaccines  

PubMed Central

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

Moingeon, Philippe

2012-01-01

267

Cell-mediated immune responses to a killed Salmonella enteritidis vaccine: lymphocyte proliferation, T-cell changes and interleukin-6 (IL-6), IL-1, IL-2, and IFN-gamma production.  

PubMed

Two experimental approaches were used to investigate the immunological responses of chickens to a commercial killed Salmonella enteritidis (SE) vaccine. In the first, the effects of host age on antigen-specific proliferative responses and cytokine production were examined. Compared with non-vaccinated controls, 4-wk-old vaccinated chickens showed higher proliferation to SE LPS and flagella. The lymphoproliferation responses to these antigens of 8-mo-old vaccinated chickens were not different compared to the non-vaccinated controls. Increased production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by antigen-stimulated splenocytes following vaccination were, in general, more often observed in 4-wk-old compared with 8-mo-old chickens, whereas serum levels of these cytokines were consistently higher in the vaccinated birds compared with controls regardless of age. The second set of experiments were designed to determine the effects of SE vaccination on mitogen- or antigen-induced splenocyte proliferation and serum nitric oxide (NO) and cytokine levels. Splenocytes from vaccinated chickens stimulated with SE flagella showed significantly increased numbers of TCRgammadelta+ cells at 7 days post-vaccination compared with non-vaccinated birds. In contrast, no differences were noted with CD4+, CD8+, or TCRalphabeta+ cells at any time points examined. Higher levels of NO production were observed following stimulation with SE flagella at 4, 7, 11, and 14 days after SE vaccination while serum levels of IFN-gamma, IL-1, IL-6, and IL-8 were elevated only at day 7 post-vaccination. In conclusion, younger chickens mounted a more robust antigen-specific immune response to the SE vaccine compared with older birds and vaccination induced not only T-cell-mediated responses but also host innate and pro-inflammatory responses. PMID:15178000

Okamura, M; Lillehoj, H S; Raybourne, R B; Babu, U S; Heckert, R A

2004-07-01

268

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

269

Anthrax vaccination strategies  

PubMed Central

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

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

2009-01-01

270

Vaccination against infectious diseases: what is promising?  

PubMed

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

Doerr, Hans Wilhelm; Berger, Annemarie

2014-12-01

271

The use of BHK suspension cells for the production of foot and mouth disease vaccines  

Microsoft Academic Search

The isolation of Baby Hamster Kidney (BHK) 21 cells and their adaptation, characterisation and development for the commercial manufacture of foot and mouth disease vaccines over a twenty year period is reviewed, including the preparation of media, handling of cell substrates and control of the physical environment during manufacture. A description is given of the successful operation of the BHK

P. J. Radlett

272

AGE DIFFERENCE IN LYMPHOCYTE PROLIFERATION, IL-2 AND IFN-Y PRODUCTION FOLLOWING SALMONELLA ENTERITIDIS VACCINATION.  

Technology Transfer Automated Retrieval System (TEKTRAN)

The present study was conducted to investigate the effect of age on cell-mediated immune responses to different antigens from Salmonella serovar Enteritidis (SE) following vaccination with the commercially available heat-the killed bacterin. Eight-month- and 4-week-old chickens were given two subcu...

273

In planta Production of Flock House Virus Transencapsidated RNA and Its Potential Use as a Vaccine.  

PubMed

We have developed a transencapsidated vaccine delivery system based on the insect virus, Flock House virus (FHV). FHV is attractive due to its small genome size, simple organization, and nonpathogenic characteristics. With the insertion of a Tobacco mosaic virus (TMV) origin of assembly (Oa), the independently replicating FHV RNA1 can be transencapsidated by TMV coat protein. In this study, we demonstrated that the Oa-adapted FHV RNA1 transencapsidation process can take place in planta, by using a bipartite plant expression vector system, where TMV coat protein is expressed by another plant virus vector, Foxtail mosaic virus (FoMV). Dual infection in the same cell by both FHV and FoMV was observed. Though an apparent classical coat protein-mediated resistance repressed FHV expression, this was overcome by delaying inoculation of the TMV coat protein vector by 3 days after FHV vector inoculation. Expression of the transgene marker in animals by these in vivo-generated transencapsidated nanoparticles was confirmed by mouse vaccination, which also showed an improved vaccine response compared to similar in vitro-produced vaccines. PMID:25432792

Zhou, Yiyang; Maharaj, Payal D; Mallajosyula, Jyothi K; McCormick, Alison A; Kearney, Christopher M

2014-11-29

274

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  

Microsoft Academic Search

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

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

2004-01-01

275

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

276

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

PubMed Central

Background Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. Methods The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions. Case description WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Discussion and evaluation Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues. Conclusions Although policy issues may be more complex for future vaccines, the lead-time between the date of product regulatory approval and a recommendation for its use in developing countries is decreasing. This study presents approaches to define in advance core data needs to support evidence-based decisions, to further decrease this lead-time, accelerating the availability of a malaria vaccine. Specific policy areas for which information should be collected are defined, including studying its use within the context of other malaria interventions. PMID:20576114

2010-01-01

277

Biological hydrogen production by dark fermentation: challenges and prospects towards scaled-up production.  

PubMed

Among different technologies of hydrogen production, bio-hydrogen production exhibits perhaps the greatest potential to replace fossil fuels. Based on recent research on dark fermentative hydrogen production, this article reviews the following aspects towards scaled-up application of this technology: bioreactor development and parameter optimization, process modeling and simulation, exploitation of cheaper raw materials and combining dark-fermentation with photo-fermentation. Bioreactors are necessary for dark-fermentation hydrogen production, so the design of reactor type and optimization of parameters are essential. Process modeling and simulation can help engineers design and optimize large-scale systems and operations. Use of cheaper raw materials will surely accelerate the pace of scaled-up production of biological hydrogen. And finally, combining dark-fermentation with photo-fermentation holds considerable promise, and has successfully achieved maximum overall hydrogen yield from a single substrate. Future development of bio-hydrogen production will also be discussed. PMID:21612910

RenNanqi; GuoWanqian; LiuBingfeng; CaoGuangli; DingJie

2011-06-01

278

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

PubMed

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

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

2008-10-01

279

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

PubMed

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

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

2013-01-01

280

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

PubMed Central

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

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

2013-01-01

281

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

PubMed Central

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

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

2001-01-01

282

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

Code of Federal Regulations, 2011 CFR

9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

2011-01-01

283

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

Code of Federal Regulations, 2010 CFR

9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

2010-01-01

284

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

Code of Federal Regulations, 2012 CFR

9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

2012-01-01

285

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

Code of Federal Regulations, 2013 CFR

9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

2013-01-01

286

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

Code of Federal Regulations, 2014 CFR

9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND...

2014-01-01

287

Combination vaccines for childhood immunization.  

PubMed

An increasing number of new and improved vaccines to prevent childhood diseases are being introduced. Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. This statement provides general guidance on the use of combination vaccines and related issues and questions. To minimize the number of injections children receive, parenteral combination vaccines should be used, if licensed and indicated for the patient's age, instead of their equivalent component vaccines. Hepatitis A, hepatitis B, and Haemophilus influenzae type b vaccines, in either monovalent or combination formulations from the same or different manufacturers, are interchangeable for sequential doses in the vaccination series. However, using acellular pertussis vaccine product(s) from the same manufacturer is preferable for at least the first three doses, until studies demonstrate the interchangeability of these vaccines. Immunization providers should stock sufficient types of combination and monovalent vaccines needed to vaccinate children against all diseases for which vaccines are recommended, but they need not stock all available types or brandname products. When patients have already received the recommended vaccinations for some of the components in a combination vaccine, administering the extra antigen(s) in the combination is often permissible if doing so will reduce the number of injections required. To overcome recording errors and ambiguities in the names of vaccine combinations, improved systems are needed to enhance the convenience and accuracy of transferring vaccine-identifying information into medical records and immunization registries. Further scientific and programmatic research is needed on specific questions related to the use of combination vaccines. PMID:10353568

1999-05-14

288

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

289

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

Code of Federal Regulations, 2011 CFR

... Notices re: worthless, contaminated, dangerous, or harmful biological...Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Notices re: worthless, contaminated, dangerous, or harmful biological...actions to the Animal and Plant Health Inspection Service...

2011-01-01

290

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

Code of Federal Regulations, 2012 CFR

... Notices re: worthless, contaminated, dangerous, or harmful biological...Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Notices re: worthless, contaminated, dangerous, or harmful biological...actions to the Animal and Plant Health Inspection Service...

2012-01-01

291

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

Code of Federal Regulations, 2013 CFR

... Notices re: worthless, contaminated, dangerous, or harmful biological...Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Notices re: worthless, contaminated, dangerous, or harmful biological...actions to the Animal and Plant Health Inspection Service...

2013-01-01

292

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

Code of Federal Regulations, 2010 CFR

... Notices re: worthless, contaminated, dangerous, or harmful biological...Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Notices re: worthless, contaminated, dangerous, or harmful biological...actions to the Animal and Plant Health Inspection Service...

2010-01-01

293

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

Code of Federal Regulations, 2014 CFR

... Notices re: worthless, contaminated, dangerous, or harmful biological...Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Notices re: worthless, contaminated, dangerous, or harmful biological...actions to the Animal and Plant Health Inspection Service...

2014-01-01

294

Biologic effects of leukocytes present in transfused cellular blood products.  

PubMed

A considerable literature has accumulated over the past decade indicating that leukocytes present in allogeneic cellular blood components, intended for transfusion, are associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, graft-versus-host disease, alloimmunization to leukocyte antigens, and the immunomodulatory effects that might influence the prognosis of patients with a malignancy. Moreover, it has become evident that such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV as well as other viruses. An interesting development that has occurred coincidentally in transfusion medicine is that agencies responsible for the provision of blood products are being designated manufacturers of biologicals. The trend among manufacturers of biologicals is to try to produce pure products to provide for the specific therapeutic need of patients. Thus, with the realization that allogeneic leukocytes and their products may have adverse biologic activities, there is increasing pressure from various sources for the reduction of the leukocyte content in allogeneic blood components to minimize the occurrence of their adverse effects. Although the threshold leukocyte number below which these effects might no longer occur is still to be determined, a 2 to 3 log10 leukocyte reduction, provided by the currently available commercial leukocyte filters, has been shown to reduce the frequency of many of such reactions. On the other hand, the immunosuppressive effects produced by the infusion of allogeneic leukocytes might be beneficial for some patients, ie, for the maintenance of kidney allografts, in possibly reducing the relapse rate in patients with inflammatory bowel diseases, and in ameliorating recurrent spontaneous abortion. Moreover, therapeutic granulocyte transfusions may be of benefit in certain well-defined categories of patients infected with bacteria, yeast, and/or fungi. These include neonates with bacterial sepsis associated with bone marrow failure as well as severely neutropenic leukemic patients with an infection unresponsive to appropriate and specific antibiotic therapy. Many of the results obtained with the use of leukocyte depletion filters are tantalizing, but the actual clinical benefit of leukodepletion has not been established in most instances, because much of the available data are retrospective or from uncontrolled clinical trials. Moreover, issues of cost-effectiveness and quality control have not been considered adequately. Properly designed prospective clinical trials are essential to provide data with which to answer such questions and also to help define the optimal conditions required for the preparation of blood components ultimately destined for clinical use. Only with the availability of such data can sound decisions be made about the clinical value of leukodepletion. PMID:8080981

Bordin, J O; Heddle, N M; Blajchman, M A

1994-09-15

295

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

296

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

PubMed

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

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

2011-01-01

297

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

298

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

299

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

Microsoft Academic Search

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

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

2008-01-01

300

Novel Expression System for Combined Vaccine Production in Edwardsiella tarda Ghost and Cadaver Cells  

Microsoft Academic Search

To develop combined vaccine systems, we have generated Edwardsiella tarda ghosts (ETG) displaying a foreign protein on the outer membrane and also Ed. tarda cadaver (ETC) expressing a heterologous protein in the cytoplasm. Green fluorescent protein (GFP) was used as a model foreign\\u000a protein. A constitutive promoter (EtPR C28-1) cloned newly from Ed. tarda was used as a promoter for

Seung Hyuk Choi; Yoon Kwon Nam; Ki Hong Kim

2010-01-01

301

Optimization of a MRC5 Cell Culture Process for the Production of a Smallpox Vaccine  

Microsoft Academic Search

A cell culture process adaptable to produce smallpox vaccine at large scale has been developed. To achieve this, Design of\\u000a Experiments (DOE) was applied to identify and optimize critical cell culture process parameters for MRC-5 cell growth and\\u000a recovery during cell expansion. For cell growth, a 25?1 partial factorial (two level, five factor, 16 conditions) study was designed to evaluate

Florence Wu; Kesav Reddy; Isabelle Nadeau; John Gilly; Sara Terpening; David J. Clanton

2005-01-01

302

The efficacy of vaccination for the eradication of rage-virus mediated zombieism. Department of Mathematics and Statistics & Department of Biology  

E-print Network

The efficacy of vaccination for the eradication of rage-virus mediated zombieism. Troy Day for a vaccine, but here I use standard techniques from mathematical epidemiology to show that such vaccines the fraction of the population that must be vaccinated to eradicate this disease as ! (R0 "1)/(1" #)R0. Here

Day, Troy

303

Messenger RNA-based vaccines: progress, challenges, applications.  

PubMed

Twenty years after the demonstration that messenger RNA (mRNA) was expressed and immunogenic upon direct injection in mice, the first successful proof-of-concept of specific protection against viral infection in small and large animals was reported. These data indicate wider applicability to infectious disease and should encourage continued translation of mRNA-based prophylactic vaccines into human clinical trials. At the conceptual level, mRNA-based vaccines-more than other genetic vectors-combine the simplicity, safety, and focused immunogenicity of subunit vaccines with favorable immunological properties of live viral vaccines: (1) mRNA vaccines are molecularly defined and carry no excess information. In the environment and upon physical contact, RNA is rapidly degraded by ubiquitous RNases and cannot persist. These characteristics also guarantee tight control over their immunogenic profile (including avoidance of vector-specific immune responses that could interfere with repeated administration), pharmacokinetics, and dosing. (2) mRNA vaccines are synthetically produced by an enzymatic process, just requiring information about the nucleic acid sequence of the desired antigen. This greatly reduces general complications associated with biological vaccine production, such as handling of infectious agents, genetic variability, environmental risks, or restrictions to vaccine distribution. (3) RNA can be tailored to provide potent adjuvant stimuli to the innate immune system by direct activation of RNA-specific receptors; this may reduce the need for additional adjuvants. The formation of native antigen in situ affords great versatility, including intracellular localization, membrane association, posttranslational modification, supra-molecular assembly, or targeted structural optimization of delivered antigen. Messenger RNA vaccines induce balanced immune responses including B cells, helper T cells, and cytotoxic T lymphocytes, rendering them an extremely adaptable platform. This article surveys the design, mode of action, and capabilities of state-of-the-art mRNA vaccines, focusing on the paradigm of influenza prophylaxis. PMID:23893949

Kramps, Thomas; Probst, Jochen

2013-01-01

304

Biological conversion of pyrolytic products to ethanol and lipids  

NASA Astrophysics Data System (ADS)

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

Lian, Jieni

305

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

306

Biological risks associated with consumption of reptile products.  

PubMed

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

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

2009-09-15

307

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

308

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

309

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

Microsoft Academic Search

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

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

2011-01-01

310

ROTAVIRUS VACCINES  

PubMed Central

Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies. PMID:17185842

Kang, G

2008-01-01

311

Plant derived veterinary vaccines  

Microsoft Academic Search

Infectious diseases remain one of the main causes of death and economic losses in animals despite the fact that prophylactic\\u000a vaccination has been extremely successful in disease prevention. New effective viral, bacterial and parasitic vaccines are\\u000a needed, but unfortunately production costs still remain prohibitive. In this respect plants can offer a valid alternative.\\u000a Production of antigenic proteins in plants relies

L. Santi

2009-01-01

312

Novel transgenic rice-based vaccines.  

PubMed

Oral vaccination can induce both systemic and mucosal antigen-specific immune responses. To control rampant mucosal infectious diseases, the development of new effective oral vaccines is needed. Plant-based vaccines are new candidates for oral vaccines, and have some advantages over the traditional vaccines in cost, safety, and scalability. Rice seeds are attractive for vaccine production because of their stability and resistance to digestion in the stomach. The efficacy of some rice-based vaccines for infectious, autoimmune, and other diseases has been already demonstrated in animal models. We reported the efficacy in mice, safety, and stability of a rice-based cholera toxin B subunit vaccine called MucoRice-CTB. To advance MucoRice-CTB for use in humans, we also examined its efficacy and safety in primates. The potential of transgenic rice production as a new mucosal vaccine delivery system is reviewed from the perspective of future development of effective oral vaccines. PMID:25027548

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

2015-04-01

313

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

314

Techniques to Improve the Characterization of Protein Particles in Biologic Drug Products  

E-print Network

novel approaches to better understand the nature of particulate matter present in biologic drug products. Silicone oil is present in many drug product contact surfaces and was chosen for further study on the effect of protein aggregation. The methods...

Toler, Maria

2012-08-31

315

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

Code of Federal Regulations, 2010 CFR

...prophylactic, or diagnostic agents considered and a statement...prophylactic, or diagnostic agent for the product that is...prophylactic, or diagnostic agent for any biological product...disclosure and be made so that intelligent and informed consent be...

2010-04-01

316

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

Code of Federal Regulations, 2011 CFR

...prophylactic, or diagnostic agents considered and a statement...prophylactic, or diagnostic agent for the product that is...prophylactic, or diagnostic agent for any biological product...disclosure and be made so that intelligent and informed consent be...

2011-04-01

317

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

Code of Federal Regulations, 2013 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES FOR BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary... (Approved by the Office of Management and Budget under control number 0579-0013) [39 FR 37763, Oct. 24, 1974,...

2013-01-01

318

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

Code of Federal Regulations, 2014 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES FOR BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary... (Approved by the Office of Management and Budget under control number 0579-0013) [39 FR 37763, Oct. 24, 1974,...

2014-01-01

319

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

Code of Federal Regulations, 2012 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES FOR BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary... (Approved by the Office of Management and Budget under control number 0579-0013) [39 FR 37763, Oct. 24, 1974,...

2012-01-01

320

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

Code of Federal Regulations, 2011 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES FOR BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary... (Approved by the Office of Management and Budget under control number 0579-0013) [39 FR 37763, Oct. 24, 1974,...

2011-01-01

321

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

Code of Federal Regulations, 2010 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES FOR BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary... (Approved by the Office of Management and Budget under control number 0579-0013) [39 FR 37763, Oct. 24, 1974,...

2010-01-01

322

21 CFR 510.4 - Biologics; products subject to license control.  

Code of Federal Regulations, 2011 CFR

...AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed...

2011-04-01

323

21 CFR 510.4 - Biologics; products subject to license control.  

Code of Federal Regulations, 2010 CFR

...AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed...

2010-04-01

324

21 CFR 510.4 - Biologics; products subject to license control.  

Code of Federal Regulations, 2014 CFR

...AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed...

2014-04-01

325

21 CFR 510.4 - Biologics; products subject to license control.  

Code of Federal Regulations, 2013 CFR

...AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed...

2013-04-01

326

21 CFR 510.4 - Biologics; products subject to license control.  

Code of Federal Regulations, 2012 CFR

...AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed...

2012-04-01

327

Development of globo-h cancer vaccine.  

PubMed

The development of anticancer vaccines requires the identification of unique epitope markers, preferably expressed exclusively on the surface of cancer cells. This Account describes the path of development of a carbohydrate-based vaccine for metastatic breast cancer, including the selection and synthesis of Globo-H as the target, the development of the vaccine conjugate and adjuvant design, the study of the immune response and consideration of class switch, and the analysis of Globo-H distribution on the surface of various cancer cells, cancer stem cells, and normal cells. The first synthesis of Globo-H was accomplished through the use of glycal chemistry; this approach delivered sufficient material for evaluation in phase I human trials. The development of a programmable one-pot synthesis method rendered the synthesis more practical and enabled the midstage proof-of-concept phase II trial and late-stage phase III trial. Finally, enzymatic synthesis of Globo-H coupled with cofactor regeneration was used for the late-stage multicenter trials and manufacture of the product. Along this path of development, it was discovered that the vaccine induced antibodies to target not only Globo-H, but also SSEA3 and SSEA4. Moreover, these three glycolipids were found to be uniquely expressed not only on the cell surface of breast cancer but on 15 additional cancer types, suggesting the broad application of this vaccine in cancer treatment and perhaps cancer prevention. In addition, a new glycolipid adjuvant was designed to target the CD1d receptor on dendritic cells and B cells for presentation to and activation of T cells to modulate the immune response and induce a class switch from IgM to IgG, thereby overcoming the common problem of carbohydrate-based vaccines that often induce mainly IgM antibodies. As demonstrated in this vaccine development, the chemical approach to the synthesis and conjugation of carbohydrate-based immunogens provides the flexibility for access to various structures and linkers to identify optimal compositions for development. The enzymatic method was then introduced to enable the practical synthesis of the vaccine candidate for clinical development and commercialization. Overall, this Account illustrates the path of development of a cancer vaccine, from selection of a unique glycan marker on breast cancer cells and the cancer stem cells as target to the use of chemistry in combination with immunology and cancer biology to enable the design and development of the Globo-H vaccine to target three specific glycan markers exclusively expressed on the cell surface of a number of different types of cancer. PMID:25665650

Danishefsky, Samuel J; Shue, Youe-Kong; Chang, Michael N; Wong, Chi-Huey

2015-03-17

328

VACCINE INFORMATION STATEMENT Influenza Vaccine  

E-print Network

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

Oklahoma, University of

329

VACCINE INFORMATION STATEMENT Influenza Vaccine  

E-print Network

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

Oklahoma, University of

330

VACCINE INFORMATION STATEMENT Influenza Vaccine  

E-print Network

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

Lien, Jyh-Ming

331

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

Federal Register 2010, 2011, 2012, 2013, 2014

...Administration, 1401 Rockville Pike (HFM-71), Rockville, MD 20852, 301-827-0314, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area). A notice in the Federal Register about last...

2013-10-02

332

Influenza vaccines: unmet needs and recent developments.  

PubMed

Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described. PMID:24475351

Noh, Ji Yun; Kim, Woo Joo

2013-12-01

333

Influenza Vaccines: Unmet Needs and Recent Developments  

PubMed Central

Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described. PMID:24475351

Noh, Ji Yun

2013-01-01

334

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

PubMed

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

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

2014-12-01

335

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

336

Attenuated and replication-competent vaccinia virus strains M65 and M101 with distinct biology and immunogenicity as potential vaccine candidates against pathogens.  

PubMed

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

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

2013-06-01

337

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. PMID:23596295

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

2013-01-01

338

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

339

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2011-06-21

340

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2012-05-03

341

Protein carriers of conjugate vaccines  

PubMed Central

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

Pichichero, Michael E

2013-01-01

342

Advances in influenza vaccination.  

PubMed

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. PMID:24991424

Reperant, Leslie A; Rimmelzwaan, Guus F; Osterhaus, Albert D M E

2014-01-01

343

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. PMID:24991424

Reperant, Leslie A.; Rimmelzwaan, Guus F.

2014-01-01

344

Argentine hemorrhagic fever vaccines.  

PubMed

Argentine hemorrhagic fever (AHF), an acute disease caused by Junin virus (JUNV, Arenaviridae), has been an important issue to public health in Argentina since the early 1950s. The field rodent Calomys musculinus is JUNV natural reservoir and human disease is a consequence of contact with infected rodents. A steady extention of AHF endemic area is being observed since the first reports of the disease. Important achievements have been made in: (a) improvement of methods for the etiological diagnosis; (b) implementation and validation of therapeutical measures; (c) development of vaccines to protect against AHF. Reference is made to different research strategies used to obtain anti-AHF vaccines in the past and anti-arenaviral diseases in the present. Information is updated on features and field performance of Candid #1 vaccine, a live attenuted vaccine currently used to prevent AHF. This vaccine was developed through a joint international effort that envisioned it as an orphan drug. With transferred technology, Argentine government was committed to be Candid #1 manufacturer and to register this vaccine as a novel medical product under the Argentine regulatory authority. Candid #1 vaccine is the first one used to control an arenaviral hemorrhagic fever, the first live viral vaccine to be manufactured and registered in Argentina, reaching its target population through governmental effort. PMID:21451263

Ambrosio, Ana; Saavedra, Maria; Mariani, Mauricio; Gamboa, Graciela; Maiza, Andrea

2011-06-01

345

Vaccines against malaria.  

PubMed

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

Ouattara, Amed; Laurens, Matthew B

2015-03-15

346

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. PMID:24967094

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

2014-01-01

347

Novel expression system for combined vaccine production in Edwardsiella tarda ghost and cadaver cells.  

PubMed

To develop combined vaccine systems, we have generated Edwardsiella tarda ghosts (ETG) displaying a foreign protein on the outer membrane and also Ed. tarda cadaver (ETC) expressing a heterologous protein in the cytoplasm. Green fluorescent protein (GFP) was used as a model foreign protein. A constitutive promoter (EtPR C28-1) cloned newly from Ed. tarda was used as a promoter for the expression of foreign protein. Comparison of the strength of the new promoter with a commercially available constitutive promoter (P(HCE)) showed higher expression levels of the novel expression system. The N-terminal domain of ice nucleation protein (InaN), an outer membrane protein of Pseudomonas syringae, was used as an anchor motif for surface display of GFP. By transformation of Ed. tarda with the constructed vectors, GFP was successfully expressed on the surface of ETG and in the cytoplasm of ETC. When compared to P(HCE) driven expression, approximately more than 2 times of GFP was expressed on ETG and in ETC by EtPR C28-1 promoter when judged by fluorescent spectrophotometry. Furthermore, significantly higher expression of GFP on the surface of ETG by EtPR C28-1 than by P(HCE) was demonstrated by serum agglutination assay. These results suggest that the newly cloned Ed. tarda constitutive promoter is capable to express foreign proteins not only on the surface of Ed. tarda ghosts but also in the cytoplasm of Ed. tarda cadavers, and can be used as an efficient promoter for the expression of heterologous antigens of the ETG and ETC-based combined vaccines. PMID:20369310

Choi, Seung Hyuk; Nam, Yoon Kwon; Kim, Ki Hong

2010-10-01

348

MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation  

Microsoft Academic Search

Over the last decade, adherent MDCK (Madin Darby canine kidney) and Vero cells have attracted considerable attention for production\\u000a of cell culture-derived influenza vaccines. While numerous publications deal with the design and the optimization of corresponding\\u000a upstream processes, one-to-one comparisons of these cell lines under comparable cultivation conditions have largely been neglected.\\u000a Therefore, a direct comparison of influenza virus production

Yvonne Genzel; Christian Dietzsch; Erdmann Rapp; Jana Schwarzer; Udo Reichl

2010-01-01

349

Chloroplast-derived vaccines against human diseases: achievements, challenges and scopes.  

PubMed

Infectious diseases represent a continuously growing menace that has severe impact on health of the people worldwide, particularly in the developing countries. Therefore, novel prevention and treatment strategies are urgently needed to reduce the rate of these diseases in humans. For this reason, different options can be considered for the production of affordable vaccines. Plants have been proved as an alternative expression system for various compounds of biological importance. Particularly, plastid genetic engineering can be potentially used as a tool for cost-effective vaccine production. Antigenic proteins from different viruses and bacteria have been expressed in plastids. Initial immunological studies of chloroplast-derived vaccines have yielded promising results in animal models. However, because of certain limitations, these vaccines face many challenges on production and application level. Adaptations to the novel approaches are needed, which comprise codon usage and choice of proven expression cassettes for the optimal yield of expressed proteins, use of inducible systems, marker gene removal, selection of specific antigens with high immunogenicity and development of tissue culture systems for edible crops to prove the concept of low-cost edible vaccines. As various aspects of plant-based vaccines have been discussed in recent reviews, here we will focus on certain aspects of chloroplast transformation related to vaccine production against human diseases. PMID:21447052

Lössl, Andreas G; Waheed, Mohammad T

2011-06-01

350

Rotavirus vaccines  

PubMed Central

Early rotavirus vaccine adopter countries in the Americas, Europe, and in Australia have documented substantial declines in rotavirus disease burden following the introduction of vaccination. However, the full public health impact of rotavirus vaccines has not been realized as they have not been introduced into routine immunization programs in countries of Africa and Asia with the highest rotavirus disease morbidity and mortality burden. In this article, we review the epidemiology of rotavirus disease, the development and current status of rotavirus vaccines including newly available vaccine impact data from early-introducer countries, and future priorities for implementation and monitoring of rotavirus vaccination programs in developing countries. PMID:22108032

Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Lopman, Benjamin; Fleming, Jessica; Lewis, Kristen; Jiang, Baoming; Gentsch, Jon; Steele, Duncan; Parashar, Umesh D

2011-01-01

351

Future directions for the development of Chlamydomonas-based vaccines.  

PubMed

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

Rosales-Mendoza, Sergio

2013-09-01

352

Volatilization and Efflux of Mercury from Biologically Productive Ocean Regions.  

NASA Astrophysics Data System (ADS)

Mercury volatilization and oceanic evasion to the atmosphere were investigated in the tropical Pacific Ocean with emphasis on the biologically productive equatorial region. Further studies were conducted at two stations in the oligiotrophic North Pacific gyre, and in the estuarine mesocosms at the Marine Ecosystems Research Laboratory (MERL), University of Rhode Island. Dissolved gaseous Hg (DGM) in the tropical Pacific along 150^circ W at 4 stations (10^circ N, 0^ circ, 5^circ S, 12^circ S) ranged from 35-85 femtomoles per liter (fM) in surface waters and from 105-185 fM in deeper waters (350-400 meters). Speciation experiments indicated that Hg^circ was the dominant form in surface waters, while evidence for (CH_3)_2Hg was found at depth. The increases of DGM with depth are consistent with a volatile Hg source in deeper waters. A significant correlation between DGM and apparent oxygen utilization (n = 23, r = 0.694) suggested bacterial methylation of Hg in the oxygen minimum zone. In equatorial Pacific surface waters (155-95 ^circ W), DGM varied between 60 and 225 fM. Elemental Hg appears to comprise the major fraction of DGM. Elevated DGM concentrations corresponded with increased chlorophyll a levels and cooler, nutrient-rich waters. These results suggest that phytoplankton might volatilize Hg in surface seawater or bacteria could produce Hg^circ in deeper waters which upwell to the sea surface. Surface waters of the equatorial Pacific were supersaturated with respect to Hg^circ (179-1769%). Local Hg effluxes, estimated with a thin-film gas exchange model, were between 225 and 1050 pmoles/m^2day. The anual Hg efflux from the equatorial Pacific, 1.6 +/- 1.3 times 10^{+6 } moles (megamoles), was estimated at 4-5% of the total global Hg flux to the atmosphere. When normalized to primary production, a yearly Hg efflux of 14 +/- 9 megamoles was predicted for the oceans. This is about 35% of the annual atmospheric Hg flux and is comparable to human-derived Hg emissions. Dissolved gaseous Hg in the MERL mesocosms ranged from <=q30 to 185 fM. In general, Hg^circ was the principal species, although (CH_3)_2Hg was detected twice. Supersaturated levels of Hg ^circ corresponded with phytoplankton blooms of Cerataulina pelagica, Leptocylindrus danicus, Leptocylindrus minimus, and Phaeocystis poucheti, suggesting that these phytoplankton could volatilize Hg in estuarine waters. Micro-flagellates may produce (CH_3) _2Hg. Mercury emanations from the mesocosms were estimated to be approximately 10% of the oceanic Hg effluxes to the atmosphere.

Kim, Jonathan Philip

353

Live attenuated vaccines against pertussis.  

PubMed

The intensive use of pertussis vaccines has dramatically reduced the incidence of whooping cough during the 20th century. However, recent outbreaks in countries with high vaccination coverage illustrate the shortcomings of current vaccination regimens, and immunity induced by the most recent, acellular vaccines wanes much faster than anticipated. As an alternative, live attenuated vaccine candidates have recently been developed in order to mimic natural infection, which induces long-lasting immunity. One of them has successfully completed a Phase I trial in humans and is now undergoing further product and clinical developments. This article describes the development of such vaccines, discusses their advantages over existing vaccines and their interesting bystander properties as powerful anti-inflammatory agents, which widens their potential use far beyond that for protection against whooping cough. PMID:25085735

Locht, Camille; Mielcarek, Nathalie

2014-09-01

354

Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants.  

PubMed

Expression of recombinant vaccine antigens and monoclonal antibodies using plant viral vectors has developed extensively during the past several years. The approach benefits from high yields of recombinant protein obtained within days after transient delivery of viral vectors to leaves of Nicotiana benthamiana, a tobacco relative. Modified viral genomes of both RNA and DNA viruses have been created. Geminiviruses such as bean yellow dwarf virus (BeYDV) have a small, single stranded DNA genome that replicates in the nucleus of an infected plant cell, using the cellular DNA synthesis apparatus and a virus-encoded replication initiator protein (Rep). BeYDV-derived expression vectors contain deletions of the viral genes encoding coat and movement proteins and insertion of an expression cassette for a protein of interest. Delivery of the geminiviral vector to leaf cells via Agrobacterium-mediated delivery produces very high levels of recombinant DNA that can act as a transcription template, yielding high levels of mRNA for the protein of interest. Several vaccine antigens, including Norwalk virus capsid protein and hepatitis B core antigen, were expressed using the BeYDV vector at levels up to 1 mg per g of leaf mass. BeYDV replicons can be stacked in the same vector molecule by linking them in tandem, which enables production of multi-subunit proteins like monoclonal antibody (mAb) heavy and light chains. The protective mAb 6D8 against Ebola virus was produced at 0.5 mg per g of leaf mass. Multi-replicon vectors could be conveniently used to produce protein complexes, e.g. virus-like particles that require two or more subunits. PMID:21358270

Chen, Qiang; He, Junyun; Phoolcharoen, Waranyoo; Mason, Hugh S

2011-03-01

355

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

Federal Register 2010, 2011, 2012, 2013, 2014

...percent of vaccines licensed in the United States are not subject to CDC notification, including vaccines for rabies, yellow fever, and typhoid. Moreover, even for the vaccines that are subject to CDC notification, the information...

2013-11-04

356

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

357

Cancer Vaccines  

MedlinePLUS

... are now giving researchers the knowledge required to design cancer treatment vaccines that can accomplish both goals ( ... al. TRICOM vector based cancer vaccines. Current Pharmaceutical Design 2006; 12(3):351–361. [PubMed Abstract] Zou ...

358

HPV Vaccine  

MedlinePLUS

... for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & ... Asthma Concussions Smart Snacking HPV Vaccine KidsHealth > Teens > Sexual Health > STDs & Other Infections > HPV Vaccine Print A A ...

359

Vaccine trials  

Microsoft Academic Search

This article reviews some of the issues involved in evaluating vaccines in humans. Vaccine trials are required for licensure\\u000a and are essential for demonsrating a vaccine’s safety and protective efficacy. The formal framework of phase I, II, and III\\u000a trials is described, with particular emphasis on the choice of hypotheses, trial design, and biases that arise in the context\\u000a of

C. P. Farrington; E. Miller

2001-01-01

360

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

PubMed Central

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

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

2008-01-01

361

The case for a rational genome-based vaccine against malaria  

PubMed Central

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

Proietti, Carla; Doolan, Denise L.

2015-01-01

362

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. PMID:21854553

Hansen, Steffi; Lehr, Claus?Michael

2012-01-01

363

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

364

Optimization of a multi-stage, multi-subunit malaria vaccine candidate for the production in Pichia pastoris by the identification and removal of protease cleavage sites.  

PubMed

We demonstrated the successful optimization of a recombinant multi-subunit malaria vaccine candidate protein for production in the methylotrophic yeast Pichia pastoris by the identification and subsequent removal of two protease cleavage sites. After observing protein degradation in the culture supernatant of a fed-batch fermentation, the predominant proteolytic fragment of the secreted recombinant protein was analyzed by mass spectrometry. The MS data indicated the cleavage of an amino acid sequence matching the yeast KEX2-protease consensus motif EKRE. The cleavage in this region was completely abolished by the deletion of the EKRE motif in a modified variant. This modified variant was produced, purified, and used for immunization of rabbits, inducing high antigen specific antibody titers (2?×?10(6) ). Total IgG from rabbit immune sera recognized different stages of Plasmodium falciparum parasites in immunofluorescence assays, indicating native folding of the vaccine candidate. However, the modified variant was still degraded, albeit into different fragments. Further analysis by mass spectrometry and N-terminal sequencing revealed a second cleavage site downstream of the motif PEVK. We therefore removed a 17-amino-acid stretch including the PEVK motif, resulting in the subsequent production of the full-length recombinant vaccine candidate protein without significant degradation, with a yield of 53?mg per liter culture volume. We clearly demonstrate that the proteolytic degradation of recombinant proteins by endogenous P. pastoris proteases can be prevented by the identification and removal of such cleavage sites. This strategy is particularly relevant for the production of recombinant subunit vaccines, where product yield and stability play a more important role than for the production of a stringently-defined native sequence which is necessary for most therapeutic molecules. Biotechnol. Bioeng. 2015;112: 659-667. © 2014 Wiley Periodicals, Inc. PMID:25335451

Spiegel, Holger; Schinkel, Helga; Kastilan, Robin; Dahm, Pia; Boes, Alexander; Scheuermayer, Matthias; Chudobová, Ivana; Maskus, Dominika; Fendel, Rolf; Schillberg, Stefan; Reimann, Andreas; Fischer, Rainer

2015-04-01

365

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

PubMed

Porcine circovirus type 2 (PCV2) vaccination is globally one of the most commonly used intervention strategies in growing pigs since several products became commercially available in 2006. While multiple trials have described the efficacy of individual PCV2 vaccines relative to non-vaccination, few studies provide product-to-product comparisons of efficacy. Given the well-documented efficacy of PCV2 vaccines, information about the comparative efficacy of available vaccines is more relevant to producers and veterinarians than comparison to non-vaccination. The objective of this study was to provide comparative estimates of changes in average daily gain effect associated with the use of the commercially available PCV2 vaccines. PubMed, CAB Abstracts, AGRICOLA, the USA Department of Agriculture Center for Veterinary Biologics database of licenses and provisions, and the proceedings of the Annual Meeting of the American Association of Swine Veterinarians, the Allen D. Leman Swine Conference, the Iowa State University Swine Disease Conference for Swine Practitioners, and the International Pig Veterinary Society Congress were used as the sources of information. Trials of licensed PCV2 vaccines administered according to manufacturers' specifications to intensively raised piglets with a known herd porcine reproductive and respiratory syndrome virus (PRRSV) status were considered relevant to the meta-analysis. Relevant studies had to report average daily gain (ADG) from weaning to finish and PCV2 infection had to be naturally occurring. PMID:25457512

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

2014-12-01

366

Bacterial protoplast-derived nanovesicles as vaccine delivery system against bacterial infection.  

PubMed

The notion that widespread infectious diseases could be best managed by developing potent, adjuvant-free vaccines has resulted in the use of various biological immune-stimulating components as new vaccine candidates. Recently, extracellular vesicles, also known as exosomes and microvesicles in mammalian cells and outer membrane vesicles in Gram-negative bacteria, have gained attention for the next generation vaccine. However, the more invasive and effective the vaccine is in delivery, the more risk it holds for severe immune toxicity. Here, in optimizing the current vaccine delivery system, we designed bacterial protoplast-derived nanovesicles (PDNVs), depleted of toxic outer membrane components to generate a universal adjuvant-free vaccine delivery system. These PDNVs exhibited significantly higher productivity and safety than the currently used vaccine delivery vehicles and induced strong antigen-specific humoral and cellular immune responses. Moreover, immunization with PDNVs loaded with bacterial antigens conferred effective protection against bacterial sepsis in mice. These nonliving nanovesicles derived from bacterial protoplast open up a new avenue for the creation of next generation, adjuvant-free, less toxic vaccines to be used to prevent infectious diseases. PMID:25506626

Kim, Oh Youn; Choi, Seng Jin; Jang, Su Chul; Park, Kyong-Su; Kim, Sae Rom; Choi, Jun Pyo; Lim, Ji Hwan; Lee, Seung-Woo; Park, Jaesung; Di Vizio, Dolores; Lötvall, Jan; Kim, Yoon-Keun; Gho, Yong Song

2015-01-14

367

Vaccinating through a lifetime: adult priorities.  

PubMed

Vaccination strategies for adults have recently been updated to include newer vaccine products and to reflect the changing epidemiology of vaccine-preventable diseases in adults. New products include vaccines against shingles and the human papillomavirus, and a combination vaccine which contains an acellular pertussis component (Tdap). In some cases, existing vaccines have been re-formulated to provide alternate routes of delivery, as is the case with the influenza vaccine, or more effective formulations, as is the case with the meningococcal vaccine. Vaccine strategies for adults are designed to respond to existing, emerging, or re-emerging infectious diseases in populations at risk. This includes the resurgence of pertussis and recent evidence showing that diabetics are at increased risk for hepatitis B. Unfortunately, large portions of the adult population do not receive recommended vaccinations. As a result, more adults die from vaccine-preventable diseases than die from motor vehicle accidents. Strategies to improve vaccine coverage include public education campaigns and making some vaccines available in nontraditional settings such as retail stores or workplaces. Within health care settings, successful strategies have included the use of standing orders, automatic reminders for physicians using the electronic health record and recall/reminder letters for patients. Appropriate use of adult vaccines plays a key role in prevention of disease and the provision of high-quality care. PMID:23444595

Nettleman, Mary D; Garcia-Chen, Vanessa

2013-01-01

368

Fas Ligand DNA Enhances a Vaccination Effect by Coadministered DNA Encoding a Tumor Antigen through Augmenting Production of Antibody against the Tumor Antigen  

PubMed Central

Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood. We examined whether administration of DNA encoding FasL gene enhanced antitumor effects in mice that were vaccinated with DNA expressing a putative tumor antigen gene, ?-galactosidase (?-gal). Growth of ?-gal-positive Colon 26 tumors was retarded in the syngeneic mice immunized with ?-gal and FasL DNA compared with those vaccinated with ?-gal or FasL DNA. We did not detect increased numbers of ?-gal-specific CD8+ T cells in lymph node of mice that received combination of ?-gal and FasL DNA, but amounts of anti-?-gal antibody increased with the combination but not with ?-gal or FasL DNA injection alone. Subtype analysis of anti-?-gal antibody produced by the combination of ?-gal and FasL DNA or ?-gal DNA injection showed that IgG2a amounts were greater in mice injected with both DNA than those with ?-gal DNA alone, but IgG2b amounts were lower in both DNA-injected than ?-gal DNA-injected mice. These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

Zhong, Boya; Ma, Guangyu; Sato, Ayako; Shimozato, Osamu; Liu, Hongdan; Shingyoji, Masato; Tada, Yuji; Tatsumi, Koichiro; Shimada, Hideaki; Hiroshima, Kenzo; Tagawa, Masatoshi

2015-01-01

369

Uv Spectroscopy in Monitoring of Biological Treatment of Washing Waters from Aromatic Polyamide Fibre Production  

Microsoft Academic Search

Aromatic polyamide fibre production wastes — aqueous solutions consisting of a mixture of dimethylacetamide and isobutyl alcohol, initial and treated with microorganisms for different times — were analyzed. Monitoring solutions with absorption in the UV region and COD allowed following biological treatment and modeling its components of the solutions. The possibility of monitoring biological treatment by UV spectroscopy was demonstrated.

A. G. Venediktova

2004-01-01

370

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. PMID:23440999

Mooney, Alaina J; Tompkins, S Mark

2013-01-01

371

9 CFR 101.3 - Biological products and related terms.  

Code of Federal Regulations, 2014 CFR

...or without the unevaluated growth products, which has been...antigenic toxin or toxic growth product, which has resulted from the growth of bacterial organisms in a...medium from which the bacterial cells have been removed,...

2014-01-01

372

9 CFR 101.3 - Biological products and related terms.  

Code of Federal Regulations, 2011 CFR

...or without the unevaluated growth products, which has been...antigenic toxin or toxic growth product, which has resulted from the growth of bacterial organisms in a...medium from which the bacterial cells have been removed,...

2011-01-01

373

9 CFR 101.3 - Biological products and related terms.  

Code of Federal Regulations, 2012 CFR

...or without the unevaluated growth products, which has been...antigenic toxin or toxic growth product, which has resulted from the growth of bacterial organisms in a...medium from which the bacterial cells have been removed,...

2012-01-01

374

9 CFR 101.3 - Biological products and related terms.  

Code of Federal Regulations, 2013 CFR

...or without the unevaluated growth products, which has been...antigenic toxin or toxic growth product, which has resulted from the growth of bacterial organisms in a...medium from which the bacterial cells have been removed,...

2013-01-01

375

9 CFR 103.1 - Preparation of experimental biological products.  

Code of Federal Regulations, 2011 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION... (Approved by the Office of Management and Budget under control number 0579-0013) [30 FR 11848, Sept. 16,...

2011-01-01

376

9 CFR 103.1 - Preparation of experimental biological products.  

Code of Federal Regulations, 2010 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION... (Approved by the Office of Management and Budget under control number 0579-0013) [30 FR 11848, Sept. 16,...

2010-01-01

377

9 CFR 103.1 - Preparation of experimental biological products.  

Code of Federal Regulations, 2013 CFR

...VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION... (Approved by the Office of Management and Budget under control number 0579-0013) [30 FR 11848, Sept. 16,...

2013-01-01

378

9 CFR 115.2 - Inspections of biological products.  

Code of Federal Regulations, 2014 CFR

...Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...appears that any such product is worthless, contaminated, dangerous, or harmful, the Secretary...distribution and sale actions to the Animal and Plant Health Inspection Service pursuant...

2014-01-01

379

9 CFR 115.2 - Inspections of biological products.  

Code of Federal Regulations, 2012 CFR

...Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...appears that any such product is worthless, contaminated, dangerous, or harmful, the Secretary...distribution and sale actions to the Animal and Plant Health Inspection Service pursuant...

2012-01-01

380

9 CFR 115.2 - Inspections of biological products.  

Code of Federal Regulations, 2011 CFR

...Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...appears that any such product is worthless, contaminated, dangerous, or harmful, the Secretary...distribution and sale actions to the Animal and Plant Health Inspection Service pursuant...

2011-01-01

381

9 CFR 115.2 - Inspections of biological products.  

Code of Federal Regulations, 2013 CFR

...Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...appears that any such product is worthless, contaminated, dangerous, or harmful, the Secretary...distribution and sale actions to the Animal and Plant Health Inspection Service pursuant...

2013-01-01

382

9 CFR 115.2 - Inspections of biological products.  

Code of Federal Regulations, 2010 CFR

...Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...appears that any such product is worthless, contaminated, dangerous, or harmful, the Secretary...distribution and sale actions to the Animal and Plant Health Inspection Service pursuant...

2010-01-01

383

Biological production of ethanol from waste gases with Clostridium ljungdahlii  

DOEpatents

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

Gaddy, James L. (Fayetteville, AR)

2000-01-01

384

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

Federal Register 2010, 2011, 2012, 2013, 2014

...Implementing the Physician Labeling Rule Content and Format Requirements; Availability...Biological Products--Implementing the PLR Content and Format Requirements.'' This guidance...assist applicants in complying with the content and format requirements of labeling...

2013-02-25

385

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

386

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

387

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

388

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

389

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

Code of Federal Regulations, 2014 CFR

37 Patents, Trademarks, and Copyrights 1 2014-07-01...2014-07-01 false Calculation of patent term extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights...

2014-07-01

390

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

Code of Federal Regulations, 2011 CFR

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

2011-01-01

391

Regulations for vaccines against emerging infections and agrobioterrorism in the United States of America.  

PubMed

The Virus-Serum-Toxin Act of 1913, as amended in 1985, provides the legal basis for the regulation of veterinary vaccines and related biological products in the United States of America (USA). The regulatory authority for the issuance of licences and permits that allow the shipment or importation of pure, safe, potent, and effective veterinary biological products lies with the Center for Veterinary Biologics (CVB), an agency of the United States Department of Agriculture (USDA). Under the standard licensing or permitting process, a manufacturer must develop and completely characterise and evaluate a product prior to licensure, and the CVB must review and evaluate the submitted information, audit and inspect the manufacturing facilities and methods of production and testing, and confirm key product test results through independent testing of product. This complete and comprehensive evaluation may not be possible in emergency situations, so processes and mechanisms are in place that allow for the more rapid availability of veterinary vaccines. Next generation vaccine development against foreign animal diseases such as foot and mouth disease is actively in progress in the USA and the authorities must ensure that there is an adequate supply of these vaccines in the National Veterinary Stockpile. PMID:17892163

Elsken, L A; Carr, M Y; Frana, T S; Brake, D A; Garland, T; Smith, K; Foley, P L

2007-08-01

392

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

393

Sex and Vaccination  

NSDL National Science Digital Library

This case study focuses on the controversy surrounding the decision by Texas Governor Rick Perry to mandate the compulsory vaccination of girls in the Texas public school system against the human papillomavirus (HPV) prior to entering the sixth grade. The interrupted case method is particularly appropriate for this subject, with successive sections providing a general overview of the disease, the reasons for and against such a mandatory vaccination program, and a disclosure of what ultimately transpired in Texas. Designed for an ethics or public policy course, the case could easily be adapted to emphasize biological and medical topics.

Eric Zavrel

2008-01-01

394

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. PMID:19837292

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

2009-01-01

395

Plant-derived virus-like particles as vaccines  

PubMed Central

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

396

Importance of systems biology in engineering microbes for biofuel production  

SciTech Connect

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

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

2009-12-02

397

BIOLOGICAL CONTROL OF ARTHROPOD PESTS IN LIVESTOCK PRODUCTION  

Technology Transfer Automated Retrieval System (TEKTRAN)

Filth flies and poultry litter beetles have a wide array of natural enemies that can be exploited for augmentative biological control. Adult flies are subject to infection with entomogenous nematodes and the fungal pathogens Entomophthora muscae and Beauveria bassiana. Of these, B. bassiana has th...

398

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

2014-01-01

399

Plant-Based Production of Recombinant Plasmodium Surface Protein Pf38 and Evaluation of its Potential as a Vaccine Candidate  

PubMed Central

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

400

Vaccine allergies  

PubMed Central

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

2014-01-01

401

Expression of recombinant vaccines and antibodies in plants.  

PubMed

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

Ko, Kisung

2014-06-01

402

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

403

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

PubMed Central

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

2014-01-01

404

Construction of Live Vaccines by Using Genetically Engineered Poxviruses: Biological Activity of Recombinant Vaccinia Virus Expressing Influenza Virus Hemagglutinin  

Microsoft Academic Search

Recombinant vaccinia viruses containing the cloned hemagglutinin (HA) gene from influenza virus were constructed. The biological activity of these poxvirus vectors was demonstrated both in vitro and in vivo. Expression of HA in cells infected with recombinant vaccinia was detected by using specific anti-HA antiserum and 125I-labeled protein A, showing that HA synthesized under the regulation of vaccinia virus was

Dennis Panicali; Stephen W. Davis; Randall L. Weinberg; Enzo Paoletti

1983-01-01

405

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. PMID:23678166

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

2013-01-01

406

BENEFICIAL USE OF ATTENUATED VACCINES IN AQUACULTURE  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

407

Biological control of Rhizoctonia solani in greenhouse bedding plant production  

E-print Network

iviichael Brown B. S, East Texas State University. Chairman of Advisory Committee: Dr . A . E . Nightingale . Isolates of Trichoderma harzianum, T. hamatum, and Gliocladium spp. capable of inhibiting the growth of Rhizoctonia solani, which may cause... experiments testing the use of Trichoderma and Gliocladium spp. have had varying degrees of success. Elad (15), using T. harzianum as a biological control organism against Rhizoctonia solani, reduced disease incidence in carnation and incr eased...

Brown, John Michael

1983-01-01

408

A turning point for natural product discovery--ESF-EMBO research conference: synthetic biology of antibiotic production.  

PubMed

Synthetic Biology is in a critical phase of its development: it has finally reached the point where it can move from proof-of-principle studies to real-world applications. Secondary metabolite biosynthesis, especially the discovery and production of antibiotics, is a particularly relevant target area for such applications of synthetic biology. The first international conference to explore this subject was held in Spain in October 2011. In four sessions on General Synthetic Biology, Filamentous Fungal Systems, Actinomyces Systems, and Tools and Host Structures, scientists presented the most recent technological and scientific advances, and a final-day Forward Look Plenary Discussion identified future trends in the field. PMID:22296491

Takano, Eriko; Bovenberg, Roel A L; Breitling, Rainer

2012-03-01

409

Production of a novel multi-epitope peptide vaccine for cancer immunotherapy in TC-1 tumor-bearing mice.  

PubMed

In our previous research, several bioinformatic strategies were utilized to design an efficient multi-epitope peptide vaccine (MEV) against cancer. The designed vaccine consists of Wilms tumor-1 (WT-1) and human papillomavirus (HPV) E7 cytotoxic T lymphocyte (CTL) epitopes, tetanus toxin fragment C (TTFrC) and HLA-DR epitope (PADRE) helper T lymphocyte (HTL) epitopes and heparin-binding hemagglutinin (HBHA) as an immunostimulatory adjuvant. All segments were fused together by suitable linkers. In the current study, we cloned and expressed the designed MEV in E. coli. We subsequently performed in vivo preventative and therapeutic assays to evaluate antitumor efficacy of the vaccine against the HPV-16 E7-expressing murine tumor cell line TC-1 as a model for cancer immunotherapy. The results showed that in preventive experiments, vaccination with MEV significantly augmented the IgG antibody titer and the percentage of tumor-free mice compared to control groups (PBS and E7). Moreover, in therapeutic experiments, vaccination with MEV led to a reduction in the number of metastatic nodules, lung weights and the ratio of lung weights to body weights compared to other groups. In sum, our epitope vaccine could efficiently induce preventive and therapeutic antitumor immunity in TC-1 tumor bearing mice. PMID:25467837

Nezafat, Navid; Sadraeian, Mohammad; Rahbar, Mohammad Reza; Khoshnoud, Mohammad Javad; Mohkam, Milad; Gholami, Ahmad; Banihashemi, Mehrzad; Ghasemi, Younes

2015-01-01

410

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

PubMed

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

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

2014-01-01

411

Filovirus vaccines  

PubMed Central

Filoviruses can cause severe and often fatal hemorrhagic fever in humans and non-human primates (NHPs). Although there are currently no clinically proven treatments for filovirus disease, much progress has been made in recent years in the discovery of therapeutics and vaccines against these viruses. A variety of vaccine platforms have been shown to be effective against filovirus infection. This review summarizes the literature in this field, focusing on vaccines that have been shown to protect NHPs from infection. Furthermore, the uses of rodent models in vaccine development, as well as correlates of immunity, are discussed. PMID:21519188

Bradfute, Steven B; Dye, John M

2011-01-01

412

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

Microsoft Academic Search

This study demonstrates the feasibility of large-scale production of murine polyomavirus VP1 protein in recombinant Escherichia coli as pentamers which are able to subsequently self-assemble in vitro into virus-like particles (VLPs). High-cell-density pH-stat fed-batch cultivation was employed to produce glutathione-S-transferase (GST)-VP1 fusion protein in soluble form. The expression of recombinant VP1 was induced with IPTG at different cell optical densities

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

2010-01-01

413

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. PMID:24735253

2014-01-01

414

Vaccines within vaccines  

PubMed Central

Adenovirus Types 4 and 7 (Ad4 and Ad7) are associated with acute respiratory distress (ARD). In order to prevent widespread Ad-associated ARD (Ad-ARD) the United States military immunizes new recruits using a safe and effective lyophilized wildtype Ad4 and Ad7 delivered orally in an enteric-coated capsule. We cloned Ad4 and Ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (HA1-con). BALB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.) and intranasally (i.n.). Ad4 induced significantly higher luciferase expression levels as compared with Ad7 by both routes. Ad7 transduction was restored using a human CD46+ transgenic mouse model. Mice immunized with serial dilutions of viruses expressing the HA1-con influenza vaccine gene were challenged with 100 MLD50 of influenza virus. Ad4 protected BALB/c mice at a lower dose by i.m. immunization as compared with Ad7. Unexpectedly, there was no difference in protection by i.n. immunization. Although Ad7 i.m. transduction was restored in CD46+ transgenic mice, protection against influenza challenge required even higher doses as compared with the BALB/c mice. However, Ad7 i.n. immunized CD46+ transgenic mice were better protected as compared with Ad4. Interestingly, the restoration of Ad7 transduction in CD46+ mice did not increase vaccine efficacy and indicates that Ad7 may transduce a different subset of cells through alternative receptors in the absence of CD46. These data indicate that both Ad4 and Ad7 can effectively induce anti-H1N1 immunity against a heterologous challenge using a centralized H1 gene. Future studies in non-human primates or human clinical trials will determine the overall effectiveness of Ad4 and Ad7 as vaccines for influenza. PMID:24280656

Weaver, Eric A

2014-01-01

415

Influenza Vaccines: A Moving Interdisciplinary Field  

PubMed Central

Vaccination is by far the most effective way of preventing morbidity and mortality due to infection of the upper respiratory tract by influenza virus. Current vaccines require yearly vaccine updates as the influenza virus can escape vaccine-induced humoral immunity due to the antigenic variability of its surface antigens. In case of a pandemic, new vaccines become available too late with current vaccine practices. New technologies that allow faster production of vaccine seed strains in combination with alternative production platforms and vaccine formulations may shorten the time gap between emergence of a new influenza virus and a vaccine becoming available. Adjuvants may allow antigen-sparing, allowing more people to be vaccinated with current vaccine production capacity. Adjuvants and universal vaccines can target immune responses to more conserved influenza epitopes, which eventually will result in broader protection for a longer time. In addition, further immunological studies are needed to gain insights in the immune features that contribute to protection from influenza-related disease and mortality, allowing redefinition of correlates of protection beyond virus neutralization in vitro. PMID:25302957

Schotsaert, Michael; García-Sastre, Adolfo

2014-01-01

416

Current status and future trends in vaccine regulation — USA  

Microsoft Academic Search

In regulating vaccines, the US Food and Drug Administration (FDA) is governed by the Code of Federal Regulations. These regulations serve as the framework for product characterization, as well as preclinical and clinical testing strategies. Novel vaccine approaches such as combination vaccines, vectored vaccines, new adjuvants, and novel delivery systems pose unique regulatory challenges for the FDA. If US licensure

Lydia A. Falk; Leslie K. Ball

2001-01-01

417

Suggested guidelines for vaccination of pigs in Korea  

PubMed Central

There is no published guideline for the vaccination to pigs even though several vaccine companies suggested the program based on their products. It is very difficult to standardize the program because most of the veterinary vaccines are containing several multivalent antigens depending on the companies. Now, we are suggesting the vaccine programs based on the current situation. PMID:25648422

Lee, Won Hyung

2015-01-01

418

Microneedle patches for vaccine delivery  

PubMed Central

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

Suh, Hyemee; Shin, Juhyung

2014-01-01

419

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

420

Increasing algal photosynthetic productivity by integrating ecophysiology with systems biology.  

PubMed

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

Peers, Graham

2014-11-01

421

Vaccination Debate  

MedlinePLUS Videos and Cool Tools

The debate over childhood vaccination and a parent’s right to refuse or delay continues to make headlines… in the wake of the recent measles outbreak. ... request is made to spread out a child’s vaccination schedule. Researchers sent out surveys to more than ...

422

DNA Vaccines  

Microsoft Academic Search

In just a few years, injection of plasmid DNA to elicit immune responses in vivo has developed from an interesting observation to a viable vaccine strategy. DNA vaccines have been shown to elicit both cellular and humoral immune responses and to be effective in a variety of preclinical bacterial, viral, and parasitic animal models. This review will discuss the current

Donna L. Montgomery; Jeffrey B. Ulmer; John J. Donnelly; Margaret A. Liu

1997-01-01

423

Malaria vaccines  

Microsoft Academic Search

Significant progress has been made in the development of the malaria vaccine during the last 20 years. Ninety percent of the 300–500 million clinical cases of malaria per year worldwide occur in Africa. Thus, research must be directed toward the 1 million African children under 5 years of age who die every year of malaria. An asexual blood-stage vaccine, capable

Roberto Amador; Manuel E. Patarroyo

1996-01-01

424

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...

425

DISINFECTION BY-PRODUCT CONTROL THROUGH BIOLOGICAL FILTRATION  

EPA Science Inventory

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

426

Bacterial and other biological systems for polyester production  

Microsoft Academic Search

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

Alexander Steinbüchel; Bernd Füchtenbusch

1998-01-01

427

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

Microsoft Academic Search

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

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

2009-01-01

428

Bovine mammary stem cells: Cell biology meets production agriculture  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

429

Pasteurella challenge and ELISA serology evaluation of broiler breeders vaccinated with live cholera vaccine.  

PubMed

Broiler breeder pullets were vaccinated against fowl cholera at 10 and 20 wk of age using a live PM-1 Pasteurella multocida vaccine administered by wing web stick. Antibody production for P. multocida was measured at vaccination and at 1-4-wk intervals following vaccination by enzyme-linked immunosorbent assay. Groups of vaccinated birds were challenged at 23 and 32 wk of age. Two doses of a live PM-1 P. multocida vaccine protected broiler breeder hens against virulent challenge up to 32 wk of age when measured antibody levels had a range of 1951-4346 and a geometric titer of 3000. PMID:9533100

Sander, J E; Resurreccion, R S; Waltman, W D; McMurray, B L

1998-01-01

430

Comparative analysis of six European influenza vaccines  

Microsoft Academic Search

Three split-virion vaccines (Vaxigrip, Begrivac, and Influsplit\\/Fluarix) and three subunit vaccines containing only viral surface glycoproteins (Influvac, Agrippai, and Fluvirin) available for the 1994–95 season were analysed by biological, molecular, and biochemical methods. Although all vaccines are required by health authorities to contain 15 µg haemagglutinin per dose of each virus strain, there were significant differences in haemagglutination titres among

I. Chaloupka; A. Schuler; M. Marschall; H. Meier-Ewert

1996-01-01

431

Some problems--and their solutions--in the production of DTP (diphtheria, tetanus, pertussis) vaccine.  

PubMed

The desirability of choosing methods and equipment to meet local needs such as yield per cycle and ready availability of components of media and other reagents, and of simple equipment such as good quality glassware, of replacement parts for more complex equipment, and, most of all, of technical assistance is emphasised. Particular emphasis is given to ways of increasing yield from agar and static-liquid culture and to simple methods of separating bacteria from large volumes of culture using bacterial-precipitants. Designs are given for simple growth and mixing vessels, including magnetically-stirred units which require a minimum of servicing. It is strongly recommended that the basic production-unit should be a simple, multipurpose, high-quality stainless-steel vessel of appropriate size: such a unit has a working-life of at least 10 years. Regardless of the type of equipment used, simple or complex, the need, at all times, for well-trained technical staff is also stressed. PMID:381075

Cameron, J

1978-01-01

432

Production of double repeated B subunit of Shiga toxin 2e at high levels in transgenic lettuce plants as vaccine material for porcine edema disease.  

PubMed

Pig edema disease is a bacterial disease caused by enterohemorrhagic Escherichia coli. E. coli produces Shiga toxin 2e (Stx2e), which is composed of one A subunit (Stx2eA) and five B subunits (Stx2eB). We previously reported production of Stx2eB in lettuce plants as a potential edible vaccine (Matsui et al. in Biosci Biotechnol Biochem 73:1628-1634, 2009). However, the accumulation level was very low, and it was necessary to improve expression of Stx2eB for potential use of this plant-based vaccine. Therefore, in this study, we optimized the Stx2eB expression cassette and found that a double repeated Stx2eB (2× Stx2eB) accumulates to higher levels than a single Stx2eB in cultured tobacco cells. Furthermore, a linker peptide between the two Stx2eB moieties played an important role in maximizing the effects of the double repeat. Finally, we generated transgenic lettuce plants expressing 2× Stx2eB with a suitable linker peptide that accumulate as much as 80 mg per 100 g fresh weight, a level that will allow us to use these transgenic lettuce plants practically to generate vaccine material. PMID:20972886

Matsui, Takeshi; Takita, Eiji; Sato, Toshio; Aizawa, Michie; Ki, Misa; Kadoyama, Yumiko; Hirano, Kenji; Kinjo, Satoko; Asao, Hiroshi; Kawamoto, Keiko; Kariya, Haruko; Makino, Sou-Ichi; Hamabata, Takashi; Sawada, Kazutoshi; Kato, Ko

2011-08-01

433

N-glycosylation of cholera toxin B subunit in Nicotiana benthamiana: impacts on host stress response, production yield and vaccine potential.  

PubMed

Plant-based transient overexpression systems enable rapid and scalable production of subunit vaccines. Previously, we have shown that cholera toxin B subunit (CTB), an oral cholera vaccine antigen, is N-glycosylated upon expression in transgenic Nicotiana benthamiana. Here, we found that overexpression of aglycosylated CTB by agroinfiltration of a tobamoviral vector causes massive tissue necrosis and poor accumulation unless retained in the endoplasmic reticulum (ER). However, the re-introduction of N-glycosylation to its original or an alternative site significantly relieved the necrosis and provided a high CTB yield without ER retention. Quantitative gene expression analysis of PDI, BiP, bZIP60, SKP1, 26S? proteasome and PR1a, and the detection of ubiquitinated CTB polypeptides revealed that N-glycosylation significantly relieved ER stress and hypersensitive response, and facilitated the folding/assembly of CTB. The glycosylated CTB (gCTB) was characterized for potential vaccine use. Glycan profiling revealed that gCTB contained approximately 38% plant-specific glycans. gCTB retained nanomolar affinity to GM1-ganglioside with only marginal reduction of physicochemical stability and induced an anti-cholera holotoxin antibody response comparable to native CTB in a mouse oral immunization study. These findings demonstrated gCTB's potential as an oral immunogen and point to a potential role of N-glycosylation in increasing recombinant protein yields in plants. PMID:25614217

Hamorsky, Krystal Teasley; Kouokam, J Calvin; Jurkiewicz, Jessica M; Nelson, Bailey; Moore, Lauren J; Husk, Adam S; Kajiura, Hiroyuki; Fujiyama, Kazuhito; Matoba, Nobuyuki

2015-01-01

434

N-Glycosylation of cholera toxin B subunit in Nicotiana benthamiana: impacts on host stress response, production yield and vaccine potential  

PubMed Central

Plant-based transient overexpression systems enable rapid and scalable production of subunit vaccines. Previously, we have shown that cholera toxin B subunit (CTB), an oral cholera vaccine antigen, is N-glycosylated upon expression in transgenic Nicotiana benthamiana. Here, we found that overexpression of aglycosylated CTB by agroinfiltration of a tobamoviral vector causes massive tissue necrosis and poor accumulation unless retained in the endoplasmic reticulum (ER). However, the re-introduction of N-glycosylation to its original or an alternative site significantly relieved the necrosis and provided a high CTB yield without ER retention. Quantitative gene expression analysis of PDI, BiP, bZIP60, SKP1, 26S? proteasome and PR1a, and the detection of ubiquitinated CTB polypeptides revealed that N-glycosylation significantly relieved ER stress and hypersensitive response, and facilitated the folding/assembly of CTB. The glycosylated CTB (gCTB) was characterized for potential vaccine use. Glycan profiling revealed that gCTB contained approximately 38% plant-specific glycans. gCTB retained nanomolar affinity to GM1-ganglioside with only marginal reduction of physicochemical stability and induced an anti-cholera holotoxin antibody response comparable to native CTB in a mouse oral immunization study. These findings demonstrated gCTB's potential as an oral immunogen and point to a potential role of N-glycosylation in increasing recombinant protein yields in plants. PMID:25614217

Hamorsky, Krystal Teasley; Kouokam, J. Calvin; Jurkiewicz, Jessica M.; Nelson, Bailey; Moore, Lauren J.; Husk, Adam S.; Kajiura, Hiroyuki; Fujiyama, Kazuhito; Matoba, Nobuyuki

2015-01-01

435

Unstructured proteins of the malaria parasite Plasmodium falciparum as vaccine candidates   

E-print Network

Malaria vaccine research has been battling with persistent challenges, including polymorphisms of vaccine antigens, difficulties with production processes, and limited immune protection against the disease. Intrinsically ...

Dhanasarnsombut, Kelwalin

2013-11-28

436

BIOLOGICALLY ACTIVE NATURAL PRODUCTS OF THE GENUS CALLICARPA?  

PubMed Central

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

JONES, WILLIAM P.; KINGHORN, A. DOUGLAS

2009-01-01

437

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

PubMed

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

Birdsall, Margaux

2011-01-01

438

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. PMID:23526951

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

2013-01-01

439

WHO Expert Committee on Biological Standardization.  

PubMed

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international recommendations for the production and control of vaccines and other biological substances, and the establishment of international biological reference materials. Following a brief introduction, the report summarizes a number of general issues brought to the attention of the Committee. The next part of the report, of particular relevance to manufacturers and national regulatory authorities, outlines the discussions held on the development of revised WHO Guidelines. Specific discussions took place on the development of WHO guidance on the nonclinical evaluation of vaccine adjuvants and adjuvanted vaccines; the quality, safety and efficacy of typhoid conjugate vaccines; and the quality, safety and efficacy of biotherapeutic protein products prepared by recombinant DNA technology. Subsequent sections of the report provide information on the current status and proposed development of international reference materials in the areas of vaccines and related substances; blood products and related substances; in vitro diagnostic device reagents; and biotherapeutics other than blood products. A series of annexes are then presented which include an updated list of WHO Recommendations, Guidelines and other documents on biological substances used in medicine (Annex 1), followed by a series of WHO Guidelines adopted on the advice of the Committee (Annexes 2-4). All additions and discontinuations made during the 2013 meeting tothe list of International Standards and Reference Panels for biological substances maintained by WHO are summarized in Annex 5. The updated full catalogue of WHO International Reference Preparations is available at: http:/www.who.int/bloodproducts/catalogue/en/. PMID:25167682

2014-01-01

440

Packet Vaccine: Black-box Exploit Detection and Signature Generation  

E-print Network

Packet Vaccine: Black-box Exploit Detection and Signature Generation XiaoFeng Wang1 , Zhuowei Li1. ABSTRACT In biology, a vaccine is a weakened strain of a virus or bac- terium that is intentionally propose a packet vaccine mechanism that ran- domizes address-like strings in packet payloads to carry out

Wang, XiaoFeng