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| |  The current vaccine against bacterial pneumonia (pneumococcus) requires a regimen of four injections given at specific intervals. In developing countries, this not only complicates the vaccination process for health workers and children, but it also is a serious obstacle for families who must travel long distances to the nearest health clinic. In addition, vaccines delivered by injection put children at increased risk for HIV, hepatitis, and other infections that may be transmitted by unsterile or reused syringes and needles.
Dr. Curtiss and his colleagues are working to develop new vaccines against bacterial pneumonia that require only a single dose, can be delivered orally, and are safe for newborns, infants, and people who are malnourished or whose immune systems are compromised. The project will formulate the vaccine with a low-cost additive derived from weakened Salmonella bacteria, which early studies suggest can enhance a vaccine’s ability to stimulate a potent immune response. |
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| | | Construct Salmonella typhimurium vaccine strains with mutations that, among other attributes, maximize immunogenicity, diminish toxicity of lipid A, reduce potential of diarrhea, and exhibit biological containment for safety | | | | | Construct plasmid vectors using three newly developed balanced-lethal vector systems to express and secrete known protective pneumococcal protein antigens encoded by codon-optimized genes | | | | | Make and evaluate recombinant strains for induction of mucosal, systemic, and cellular immune responses and ability to induce protective immunity | | | | | Identify new pneumococcal protective antigens and define antigenic diversity/cross reactivity using Salmonella pneumoniae serotypes prevalent in the developing world | | | | | Conduct safety evaluations for fetuses, newborn, infant, adult, and immunocompromised or malnourished mice | | | | | Evaluate host-vector system for repetitive immunizations to induce protective immunity to multiple antigens independent of order of immunizations | | | | | Evaluate recombinant Salmonella typhi vaccine constructs to validate importance of the RpoS+ phenotype to maximize immunogenicity | | | | | Design, construct, and characterize optimal recombinant S. typhi vaccines for clinical trials | | | | | Conduct clinical trials in the U.S. and Korea with GLP laboratory-grown cultures and GMP manufactured vaccines | | | | | Investigate a boosting vaccination for inducing life-long immunity to infection with S. pneumoniae of diverse serotypes prevalent in the developing world | | |
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| | | Designed and evaluated a number of modified S. typhimurium strains with a number of the following characteristics:
· Regulated delayed attenuation,
· Regulated delayed expression of pneumococcal protective antigens,
· Decreased toxicity and induction of gastroenteritis with fluid loss,
· Decreased immune responses to serotype-specific and immunodominant Salmonella antigens,
· Enhanced genetic stability,
· Enhanced induction of mucosal and systemic antibody responses to pneumococcal antigens,
· Means to confer biological containment to lessen vaccine persistence in the immunized individual and vaccine survival if excreted. | | | | | Demonstrated that these S. typhimurium vaccine constructs induce high-level protective immunity in mice challenged with virulent S. pneumoniae and are safe for oral immunization of newborn mice. | | | | | Demonstrated passive transfer of protective immunity to pneumococcal challenge by transfer of either serum antibodies or T cells from orally immunized mice to naive mice that have not been immunized. | | | | | Constructed three S. typhi strains with these attributes. These strains are being evaluated for all genetic attributes for genetic stability and for complete safety when inoculated orally into day-of-birth mice. | | | | | Development of recombinant attenuated Salmonella vaccine strains with multiple balanced-lethal plasmids for expression of multiple protective antigens. | | | | | Regulated delayed expression of protective antigen synthesis and regulated delayed attenuation to enhance the vaccine immunogenicity. | | |
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| | | University of Alabama, Alabama, United States - US | | | | | Trinity University, Texas, United States - US | | | | | Tufts University, Massachusetts, United States - US | | | | | Pusan National University , Pusan National University, Pusan, Korea, Democratic People's Republic of - KP | | | | | International Vaccine Institute, Seoul, Korea, Democratic People's Republic of - KP | | | | | Duke University, North Carolina, United States - US | | | | | University of Adelaide, Adelaide, Australia - AU | | | | | University of Melbourne, Melbourne, Australia - AU | | |
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