The Food and Drug Administration Safety and Innovation Act (P.L. 112-144)

The Food and Drug Administration Safety and Innovation Act (P.L. 112-144)

Date: August 21, 2012
Creator: Thaul, Susan; Bagalman, Erin; Corby-Edwards, Amalia K.; Glassgold, Judith M.; Johnson, Judith A.; Lister, Sarah A. et al.
Description: This report provides a brief policy background narrative and an overview of provisions for each title of the Food and Drug Administration Safety and Innovation Act (FDASIA), P.L. 112-144. The legislation amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to expand the authority of the Food and Drug Administration (FDA) in performing its human drug, biological product, and medical device responsibilities.
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Smallpox Vaccine Stockpile and Vaccination Policy

Smallpox Vaccine Stockpile and Vaccination Policy

Date: September 9, 2002
Creator: Johnson, Judith A
Description: None
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Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1985 Annual Report.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1985 Annual Report.

Date: June 1, 1986
Creator: Kaattari, Stephen L.
Description: Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's second year was to chemically modify the major antigens of Renibacteirium salmoninarum, immunize coho salmon (Oncorhynchus kisutch), and to test the immunogenicity of the preparations used. Immunogenicity of the antigenic material was tested by (1) admixture experiments, using whole KD cells with muramyl dipepetide, Vibrio anguillarum extract, E. coli lipopolysaccharide, or Mycobacterium tuberculosis in Freund's complete ...
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Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1986 Annual Report.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1986 Annual Report.

Date: June 1, 1987
Creator: Kaattari, Stephen L.
Description: Bacterial kidney disease (BRD) has been and remains a chronic contributory problem limiting the productivity of salmon of the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon of Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem,and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's third year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various chemical conjugates of Renibacterium salmoninarum cells and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (cellular proliferation), and the kinetics of mortality after Lethal injections of the bacterium. An important facet of this ...
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Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1987 Annual Report.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1987 Annual Report.

Date: June 1, 1988
Creator: Kaattari, Stephen
Description: Bacterial kidney disease (BKD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's fourth year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various--chemical conjugates of Renibacterium salmoninarum cell and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (chemiluminescence), and the kinetics of mortality after lethal injections of the bacteria. The studies completed this year have: ...
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Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1988 Final Report.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1988 Final Report.

Date: August 1, 1989
Creator: Kaattari, Stephen L.
Description: Bacterial kidney disease of salmonids is a very complex disease which appears to exploit a variety of pathogenic mechanisms. An understanding of these mechanisms is essential to the development of efficacious vaccines. It has become well established from the studies published .in this report and those of others that soluble antigens which are secreted by Renibacterium salmoninarum have toxigenic potential. If they are found to be responsible for mortality, the development of toxoid(s) could be paramount to the production of a vaccine. One must, however, be circumspect in producing a vaccine. A thorough knowledge, not only of the pathogen, but also of the immune system of the host is an absolute requirement. This becomes of particular importance when dealing with fish diseases, since the field of fish immunology is still within its infancy. This lack of knowledge is particularly felt when the induction of a prophylactic immune response concomitantly leads to pathological side effects which may be as destructive as the original infection. Indeed, it appears that some aspects of BKD may be due to the induction of hypersensitivity reactions. If such immunopathologies are expressed, it is prudent to thoroughly evaluate the nature of the immunoprophylaxis to insure that these ...
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Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1984 Annual Report.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1984 Annual Report.

Date: June 1, 1985
Creator: Kaattari, Stephen L.
Description: The data presented here demonstrate that there is some variability to the antigenic structure of KDB. Although gel filtration of all antigenic preparations revealed a wide range of sizes for antigens, resolution on a denaturing gel revealed relatively few protein bands and immunological assays revealed the same (3) low number of antigens. It is of particular interest that there seems to be a protein of 60 kd in all preparations, but that there are not larger individual molecular species. This, in turn indicates that the larger molecular weight species detected in gel filtration are most likely aggregates or membrane fragments composed of a lower molecular weight subunit. Use of ultrafiltration of KDM-2 medium appears to be successful in eliminating contamination of high molecular weight material found in KDM-2. There appears to be no alteration in the number of soluble antigens produced by growth in either medium, nor in the number of proteins, as detected by SDS-PAGE. However, soluble antigens isolated from UF-KDM-2 does appear to have greater heterogeneity in their isoelectric focusing (IEF) patterns than those from UF-KDM-2. Also, although there does appear to be an extended lag period in KDB growth on UF-KDM-2, there is no alteration in final ...
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Biochemical and biophysical characterization of the major outer surface protein, OSP-A from North American and European isolates of Borrelia burgdorferi

Biochemical and biophysical characterization of the major outer surface protein, OSP-A from North American and European isolates of Borrelia burgdorferi

Date: December 31, 1995
Creator: McGrath, B.C.; Dunn, J.J.; France, L.L.; Jaing, W.; Polin, D.; Gorgone, G. et al.
Description: Lyme borreliosis, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in North America and Western Europe. As the major delayed immune response in humans, a better understanding of the major outer surface lipoproteins OspA and OspB are of much interest. These proteins have been shown to exhibit three distinct phylogenetic genotypes based on their DNA sequences. This paper describes the cloning of genomic DNA for each variant and amplification of PCR. DNA sequence data was used to derive computer driven phylogenetic analysis and deduced amino acid sequences. Overproduction of variant OspAs was carried out in E. coli using a T7-based expression system. Circular dichroism and fluorescence studies was carried out on the recombinant B31 PspA yielding evidence supporting a B31 protein containing 11% alpha-helix, 34% antiparallel beta-sheet, 12% parallel beta sheet.
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Energy Systems and Population Health

Energy Systems and Population Health

Date: April 12, 2004
Creator: Ezzati, Majid; Bailis, Rob; Kammen, Daniel M.; Holloway, Tracey; Price, Lynn; Cifuentes, Luis A. et al.
Description: It is well-documented that energy and energy systems have a central role in social and economic development and human welfare at all scales, from household and community to regional and national (41). Among its various welfare effects, energy is closely linked with people s health. Some of the effects of energy on health and welfare are direct. With abundant energy, more food or more frequent meals can be prepared; food can be refrigerated, increasing the types of food items that are consumed and reducing food contamination; water pumps can provide more water and eliminate the need for water storage leading to contamination or increased exposure to disease vectors such as mosquitoes or snails; water can be disinfected by boiling or using other technologies such as radiation. Other effects of energy on public health are mediated through more proximal determinants of health and disease. Abundant energy can lead to increased irrigation, agricultural productivity, and access to food and nutrition; access to energy can also increase small-scale income generation such as processing of agricultural commodities (e.g., producing refined oil from oil seeds, roasting coffee, drying and preserving fruits and meats) and production of crafts; ability to control lighting and heating allows education ...
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Modeling the effects of updating the influenza vaccine on the efficacy of repeated vaccination

Modeling the effects of updating the influenza vaccine on the efficacy of repeated vaccination

Date: October 1, 2000
Creator: Smith, D.J. & Lapedes, A.S.
Description: No abstract prepared.
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MODELING THE EFFECTS OF UPDATING THE INFLUENZA VACCINE ON THE EFFICACY OF REPEATED VACCINATION.

MODELING THE EFFECTS OF UPDATING THE INFLUENZA VACCINE ON THE EFFICACY OF REPEATED VACCINATION.

Date: November 1, 2000
Creator: SMITH, D.; LAPEDES, A. & AL, ET
Description: The accumulated wisdom is to update the vaccine strain to the expected epidemic strain only when there is at least a 4-fold difference [measured by the hemagglutination inhibition (HI) assay] between the current vaccine strain and the expected epidemic strain. In this study we investigate the effect, on repeat vaccines, of updating the vaccine when there is a less than 4-fold difference. Methods: Using a computer model of the immune response to repeated vaccination, we simulated updating the vaccine on a 2-fold difference and compared this to not updating the vaccine, in each case predicting the vaccine efficacy in first-time and repeat vaccines for a variety of possible epidemic strains. Results: Updating the vaccine strain on a 2-fold difference resulted in increased vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged. Conclusions: These results suggest that updating the vaccine strain on a 2-fold difference between the existing vaccine strain and the expected epidemic strain will increase vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged.
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Modeling the effects of prior infection on vaccine efficacy

Modeling the effects of prior infection on vaccine efficacy

Date: November 1, 1997
Creator: Smith, D. J.; Forrest, S.; Ackley, D. H. & Perelson, A. S.
Description: We performed computer simulations to study the effects of prior infection on vaccine efficacy. We injected three antigens sequentially. The first antigen, designated the prior, represented a prior infection or vaccination. The second antigen, the vaccine, represented a single component of the trivalent influenza vaccine. The third antigen, the epidemic, represented challenge by an epidemic strain. For a fixed vaccine to epidemic strain cross-reactivities to the vaccine and to the epidemic strains. We found that, for many cross-reactivities, vaccination, when it had been preceded by a prior infection, provided more protection than vaccination alone. However, at some cross-reactivities, the prior infection reduced protection by clearing the vaccine before it had the chance to produce protective memory. The cross-reactivities between the prior, vaccine and epidemic strains played a major role in determining vaccine efficacy. This work has applications to understanding vaccination against viruses such as influenza that are continually mutating.
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Progress in rapid detection and identification of unknown human and agricultural pathogens

Progress in rapid detection and identification of unknown human and agricultural pathogens

Date: August 13, 1999
Creator: Barnes, T; Holzrichter, J F & Milanovich, F P
Description: The medical industry is driving pathogen detection technology from its present characteristics of $50/sample, 100 sample capability systems, with several day time responses, having several percent error rates in reported outcomes. The systems described above are capable of providing samples at < $5/test, managing several million samples, < 1-hour cycle times, (or just minutes in some cases) and < 0.1% error rates. Because of their importance to the medical and agricultural communities, all ''important'' pathogens will have detection kits available (within air transport times, anywhere in the world) by 2020, and the most well known pathogens will have kits available within a few years. Many are available now. Because of the importance of the food supply to modern nations, these technologies will be employed everywhere in this industry. For example, the United States imports 30 B tons of food a year, but inspects < 1%. Portable inspection systems will make it possible to test for dangerous pathogens in feed lots, food processing plants, markets, and points of use. Outbreaks of animal or plant disease will be immediately detectable using field instrumentation, and more complex samples can be sent to central testing laboratories where more sophisticated test systems will be available. ...
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Advanced Algorithms for Rapidly Reconstructing Clandestine Releases of Biological Agents in Urban Areas

Advanced Algorithms for Rapidly Reconstructing Clandestine Releases of Biological Agents in Urban Areas

Date: February 25, 2000
Creator: Shinn, J.H.; Hall, C.H.; Neher, L.A.; Wilder, F.J.; Gouveia, D.W.; Layton, D.W. et al.
Description: As the United States plays a greater role in the 21st Century as global peacekeeper and international defender of human rights and democratic principles, there is an increasing likelihood that it will become the focus of acts of terrorism. Such acts of terrorism--sometimes described as ''asymmetric''--could involve the threat or use of weapons of mass destruction (WMD), particularly those considered unconventional, which include ones designed to release chemical or biological agents. In fact, biological agents are of great concern because, as noted by D.A. Henderson of the Center for Civilian Biodefense Studies at Johns Hopkins University in Baltimore, MD, ''... with shortages of hospital space, vaccines, antibiotics, there would be chaos.'' (Williams, 2000). Unfortunately, potential aggressor nations, terrorist groups, and even individuals, can, for a modest cost and effort, develop covert capabilities for manufacturing, transporting, and offensively using biological weapons of mass destruction. Furthermore, there is evidence to indicate that terrorist increasingly are targeting civilian populations--in order to inflict indiscriminate casualties--as well as other more traditional targets such as symbolic buildings or organizations (see Tucker, 1999), which suggest that introducing rapid treatment after a biological event may be more practical than concentrating on prevention (see Siegrist, 1999), especially because sensors ...
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Science and Technology Challenges for Homeland Security

Science and Technology Challenges for Homeland Security

Date: March 24, 2006
Creator: Murray, C A
Description: Preventing and protecting against catastrophic terrorism is a complex and dynamic challenge. Small groups or individuals can use advanced technology to cause massive destruction, and the rapid pace of technology and ease of information dissemination continually gives terrorists new tools. A 100% defense is not possible. It's a numbers problem--there are simply too many possible targets to protect and too many potential attack scenarios and adversaries to defend against. However, science and technology (S&T) is a powerful force multiplier for defense. We must use S&T to get ahead of the game by making terrorist attacks more difficult to execute, more likely to be interdicted, and less devastating in terms of casualties, economic damage, or lasting disruption. Several S&T areas have potential to significantly enhance homeland security efforts with regard to detecting radiation, pathogens, explosives, and chemical signatures of weapons activities. All of these areas require interdisciplinary research and development (R&D), and many critically depend on advances in materials science. For example, the science of nuclear signatures lies at the core of efforts to develop enhanced radiation detection and nuclear attribution capabilities. Current radiation detectors require cryogenic cooling and are too bulky and expensive. Novel signatures of nuclear decay, new detector ...
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EpiPOD : community vaccination and dispensing model user's guide.

EpiPOD : community vaccination and dispensing model user's guide.

Date: January 9, 2009
Creator: Berry, M.; Samsa, M.; Walsh, D. & Sciences, Decision and Information
Description: EpiPOD is a modeling system that enables local, regional, and county health departments to evaluate and refine their plans for mass distribution of antiviral and antibiotic medications and vaccines. An intuitive interface requires users to input as few or as many plan specifics as are available in order to simulate a mass treatment campaign. Behind the input interface, a system dynamics model simulates pharmaceutical supply logistics, hospital and first-responder personnel treatment, population arrival dynamics and treatment, and disease spread. When the simulation is complete, users have estimates of the number of illnesses in the population at large, the number of ill persons seeking treatment, and queuing and delays within the mass treatment system--all metrics by which the plan can be judged.
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Agricultural pathogen decontamination technology-reducing the threat of infectious agent spread.

Agricultural pathogen decontamination technology-reducing the threat of infectious agent spread.

Date: October 1, 2005
Creator: Betty, Rita G.; Bieker, Jill Marie & Tucker, Mark David
Description: Outbreaks of infectious agricultural diseases, whether natural occurring or introduced intentionally, could have catastrophic impacts on the U.S. economy. Examples of such agricultural pathogens include foot and mouth disease (FMD), avian influenza (AI), citrus canker, wheat and soy rust, etc. Current approaches to mitigate the spread of agricultural pathogens include quarantine, development of vaccines for animal diseases, and development of pathogen resistant crop strains in the case of plant diseases. None of these approaches is rapid, and none address the potential persistence of the pathogen in the environment, which could lead to further spread of the agent and damage after quarantine is lifted. Pathogen spread in agricultural environments commonly occurs via transfer on agricultural equipment (transportation trailers, tractors, trucks, combines, etc.), having components made from a broad range of materials (galvanized and painted steel, rubber tires, glass and Plexiglas shields, etc), and under conditions of heavy organic load (mud, soil, feces, litter, etc). A key element of stemming the spread of an outbreak is to ensure complete inactivation of the pathogens in the agricultural environment and on the equipment used in those environments. Through the combination of enhanced agricultural pathogen decontamination chemistry and a validated inactivation verification methodology, important technologies ...
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FEASIBILITY OF THE AEROSOL-TO-LIQUID PARTICLE EXTRACTION SYSTEM (ALPES) FOR COLLECTION OF VIABLE FRANCISELLA SP.

FEASIBILITY OF THE AEROSOL-TO-LIQUID PARTICLE EXTRACTION SYSTEM (ALPES) FOR COLLECTION OF VIABLE FRANCISELLA SP.

Date: August 7, 2006
Creator: Heitkamp, M
Description: Several Biowatch monitoring sites in the Houston area have tested positive for Francisella tularensis and there is a need to determine whether natural occurring Francisella-related microorganism(s) may be responsible for these observed positive reactions. The collection, culturing and characterization of Francisella-related natural microorganisms will provide the knowledge base to improve the future selectivity of Biowatch monitoring for Francisella. The aerosol-to-liquid particle extraction system (ALPES) is a high-efficiency, dual mechanism collection system that utilizes a liquid collection medium for capture of airborne microorganisms. Since the viability of microorganisms is preserved better in liquid medium than on air filters, this project was undertaken to determine whether Francisella philomiragia and Francisella tularensis LVS maintain acceptable viability in the continuous liquid recirculation, high direct current voltage and residual ozone concentrations which occur during ALPES operation. Throughout a series of preliminary trial runs with representative gram-negative and gram-positive microorganisms, several design modifications and improvements to the ALPES optimized liquid handling, electrical stability, sampling and overall performance for biological sampling. Initial testing with Francisella philomiragia showed viability was preserved better in PBS buffer than HBSS buffer. Trial runs at starting cell concentrations of 1.8 x 10{sup 6} and 2.5 x 10{sup 4} CFU/L showed less than ...
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Science and engineering of large scale socio-technical simulations.

Science and engineering of large scale socio-technical simulations.

Date: January 1, 2001
Creator: Barrett, C. L. (Christopher L.); Eubank, S. G. (Stephen G.); Marathe, M. V. (Madhav V.); Mortveit, H. S. (Henning S.) & Reidys, C. M. (Christian M.)
Description: Computer simulation is a computational approach whereby global system properties are produced as dynamics by direct computation of interactions among representations of local system elements. A mathematical theory of simulation consists of an account of the formal properties of sequential evaluation and composition of interdependent local mappings. When certain local mappings and their interdependencies can be related to particular real world objects and interdependencies, it is common to compute the interactions to derive a symbolic model of the global system made up of the corresponding interdependent objects. The formal mathematical and computational account of the simulation provides a particular kind of theoretical explanation of the global system properties and, therefore, insight into how to engineer a complex system to exhibit those properties. This paper considers the methematical foundations and engineering princaples necessary for building large scale simulations of socio-technical systems. Examples of such systems are urban regional transportation systems, the national electrical power markets and grids, the world-wide Internet, vaccine design and deployment, theater war, etc. These systems are composed of large numbers of interacting human, physical and technological components. Some components adapt and learn, exhibit perception, interpretation, reasoning, deception, cooperation and noncooperation, and have economic motives as well as ...
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THE JOINT NATIONAL INSTITUTES OF HEALTH-ATOMIC ENERGY COMMISSION ZONAL CENTRIFUGE DEVELOPMENT PROGRAM, SEMIANNUAL REPORT, JANUARY 1-JUNE 30, 1963

THE JOINT NATIONAL INSTITUTES OF HEALTH-ATOMIC ENERGY COMMISSION ZONAL CENTRIFUGE DEVELOPMENT PROGRAM, SEMIANNUAL REPORT, JANUARY 1-JUNE 30, 1963

Date: October 11, 1963
Creator: Anderson, N.G.
Description: None
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Evolving T-cell vaccine strategies for HIV, the virus with a thousand faces

Evolving T-cell vaccine strategies for HIV, the virus with a thousand faces

Date: January 1, 2009
Creator: Korber, Bette
Description: HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effect (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials ...
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Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination

Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination

Date: January 1, 2009
Creator: Korber, Bette; Fischer, William & Wallstrom, Timothy
Description: An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. ...
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Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

Date: March 29, 2010
Creator: Segelke, B; Hok, S; Lao, V; Corzett, M & Garcia, E
Description: The proposed research was motivated by an interest in understanding Y. pestis virulence mechanisms and bacteria cell-cell communication. It is expected that a greater understanding of virulence mechanisms will ultimately lead to biothreat countermeasures and novel therapeutics. Y. pestis is the etiological agent of plague, the most devastating disease in human history. Y. pestis infection has a high mortality rate and a short incubation before mortality. There is no widely available and effective vaccine for Y. pestis and multi-drug resistant strains are emerging. Y. pestis is a recognized biothreat agent based on the wide distribution of the bacteria in research laboratories around the world and on the knowledge that methods exist to produce and aerosolize large amounts of bacteria. We hypothesized that cell-cell communication via signaling molecules, or quorum sensing, by Y. pestis is important for the regulation of virulence factor gene expression during host invasion, though a causative link had never been established. Quorum sensing is a mode of intercellular communication which enables orchestration of gene expression for many bacteria as a function of population density and available evidence suggests there may be a link between quorum sensing and regulation of Y. pesits virulence. Several pathogenic bacteria have been ...
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The race between infection and immunity - how do pathogens set the pace?

The race between infection and immunity - how do pathogens set the pace?

Date: January 1, 2009
Creator: Ribiero, Ruy M
Description: Infection is often referred to as a race between pathogen and immune response. This metaphor suggests that slower growing pathogens should be more easily controlled. However, a growing body ofevidence shows that many chronic infections are caused by failure to control slow growing pathogens. The slow growth of pathogens appears to directly affect the kinetics of the immune response. Compared with the response to fast growing pathogens, the T cell response to slow pathogens is delayed in its initiation, lymphocyte expansion is slow and the response often fails to clear the pathogen, leading to chronic infection. Understanding the 'rules ofthe race' for slow growing pathogens has important implications for vaccine design and immune control of many chronic infections.
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