D W Metzger

..These findings demonstrate the effectiveness of combining PspA and IL-12 at mucosal sites to achieve optimal antibody-mediated opsonization and killing of S. pneumoniae...

..Studies examining the efficacy of IL-12-mediated effects on protective antibody response in the mouse model are summarized in this review...

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..Collectively, these results provide evidence that a major role of IgA is to facilitate presentation of Ag to mucosal T cells. IL-12 treatment can overcome IgA deficiency by providing adequate T cell priming during vaccination...

..We conclude that Fc receptor-mediated phagocytosis plays a pivotal role in clearance of respiratory virus infections...

..These results are the first results to demonstrate that IgA-mediated protection against lethal respiratory tularemia occurs after mucosal vaccination with inactivated F. tularensis LVS...

..tularensis, a category A biothreat agent. In summary, these studies show for the first time the use of FcRs as a highly effective vaccination strategy against a highly virulent mucosal intracellular pathogen...

..Thus, this study provides the first evidence for the therapeutic use of Abs in Francisella-infected individuals...

..We conclude that Th17-mediated allergic lung inflammation that becomes dominant in the absence of effective IFN-gamma signaling can be effectively suppressed by IL-12 through an IL-10-dependent mechanism...

..These findings show for the first time that soluble IL-12 delivered in serves as a powerful respiratory adjuvant for protective antiviral immunity...

..CONCLUSIONS: Porcine extracellular matrix elicits an immune response that is predominately Th2-like, consistent with a remodeling reaction rather than rejection...

..The sodB(Ft) mutant also was significantly attenuated for virulence in mice. Thus, this study has identified sodB as an important F. tularensis virulence factor...

..These results demonstrate that exogenous IL-12 delivered intranasally can prevent respiratory tularemia through a mechanism that is at least partially dependent upon the expression of IFN-gamma and CD8 T cells...

..tularensis. Thus, novel vaccine approaches should be designed to induce robust antibody and cell-mediated immune responses to this pathogen...

..We conclude that i.n vaccination in the presence of IL-12 is able to enhance systemic and mucosal immune responses to pneumococci and efficiently protect against both invasive infection and bacterial carriage...

..These results indicate that FcgammaR signaling primarily mediates the augmented serum TNF-alpha response to LPS caused by EIgG...

..The results demonstrate the critical role of secretory IgA in protection against pneumococcal nasal colonization and suggest that directed targeting to mucosal tissues will be needed for effective vaccination in humans...

..The results indicate that IFN-gamma is secreted in response to respiratory infection with F. tularensis LVS, and that NK cells are the early responders responsible for IFN-gamma secretion...

..n. vaccination of neonatal mice in the presence of IL-12 is able to enhance IFN-gamma dependent ME mucosal and systemic immune responses to pneumococci and efficiently protect against both OM and invasive infection...

..To conclude, this study demonstrates that SodB and SodC act to confer protection against host-derived oxidants and contribute to intramacrophage survival and virulence of F. tularensis in mice...

..Collectively, this study describes an improved live vaccine candidate against respiratory tularemia that has an attenuated virulence and enhanced protective efficacy than the LVS...

..Cumulatively, our findings provide compelling evidence that growth in BHI yields bacteria which recapitulate the phenotype of Francisella organisms that have emerged from macrophages...

..The results demonstrate that azithromycin can be inhibitory with regard to protective immune responsiveness...

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..To conclude, this study demonstrates that ctu contributes to intracellular survival, in vivo growth, and pathogenesis. However, ctu is not an absolute requirement for the virulence of F. tularensis Schu S4 in mice...

..e., serum IgG2a). Thus, IL-12 can be delivered safely and effectively by the i.n. route, a finding which may allow IL-12 to fulfill its clinical potential...

..Thus, IFN-gamma, although probably facilitating induction of specific anti-influenza adaptive immunity, suppresses innate protection against extracellular bacterial pathogens in the lung...

..n. vaccination. In addition, in the young mice CLN play a more important role than NALT for induction of protective mucosal and systemic antibody responses following i.n. immunization...

..These findings indicate that IL-17 is a key mediator of airway inflammation in the absence of T-bet. The results of this study suggest a possible target for therapeutic intervention of human asthma...

..Our results show that an absence of IL-10 at the time of primary infection leads to enhanced local virus-specific antibody production and, thus, increased protection against influenza A virus infection...

..Therefore, SIS implantation does not increase susceptibility to viral or bacterial pathogenic agents...

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..The findings show that IL-12 and IFN-gamma can mediate a protective effect against respiratory infection caused by extracellular bacterial pathogens...

..The results indicate that Ag-specific B cells are required at mucosal surfaces for induction of inflammation and likely function as major APCs in the lung for soluble protein Ags...

..The data suggest that IL-12 treatment during CVB4-V infection is able to suppress the immunopathological mechanisms that lead to chronic disease...

..We conclude that, in contrast to xenotransplantation of whole organs, naturally-occurring anti-alpha gal antibodies do not influence the ability of xenogeneic extracellular matrices to serve as bioscaffolds for tissue remodeling...

..In summary, the results demonstrate the safety, immunogenicity, and protective efficacy of i.n. administered iYp plus IL-12 in a mouse model of pneumonic plague...

..tularensis. Further, a mutant in FTL0552 or the comparable locus in SchuS4 (FTT1557c) may be an alternative candidate vaccine for tularemia...

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..Thus, this study showed that in a small series of patients the SIS elicits an antibody response without clinical rejection of the xenograft and minimal postoperative complications...

..In addition, we discuss various mucosal vaccine antigens, mucosal adjuvants and mucosal delivery systems...

..Funds requested in this application will be used primarily to allow new investigators with limited resources (e.g., R21 recipients) as well as trainees, to participate in these meetings. ..

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..The results of these studies will ultimately be used to evaluate new mucosal vaccination strategies and new vaccine candidates against human respiratory infection with F. tularensis. ..

..The ultimate goal is to exploit the information obtained in order to understand the requirements for induction of protective pulmonary immunity and to design effective mucosal vaccine adjuvants for use in humans. ..

..This year's topics will be: Advances in Biotechnology, Immune Regulation, Biodefense and Emerging Diseases, The Immune Response to Infection, and Strategies in Immunotherapy. ..

..pneumoniae. The bacterial genes identified in this project can be targeted to treat and prevent S. pneumoniae disease by disarming the immune evasion arsenals of S. pneumoniae through novel anti-bacterial drugs and vaccines. ..

..The ultimate goal is to exploit the information obtained in order to understand the requirements for induction of protective pulmonary immunity and to design effective mucosal vaccine adjuvants for use in humans. ..

..The ultimate goal is to exploit the information obtained in order to understand the requirements for induction of protective pulmonary immunity and to design effective mucosal vaccine adjuvants for use in humans. ..

..The results of this study will provide important insight into the roles of IL-12 and IgA in controlling immunity, and could have immediate impact on human health. ..

..Current vaccines are of only limited effectiveness. Thus, the use of IL-12 as a vaccine adjuvant may provide a novel approach for protection against these diseases and could have immediate impact on human health. ..

..The results will provide important insight into the mechanisms responsible for successful xenogeneic transplantation and could lead to targeted cytokine therapies to prevent tissue rejection. ..

..Thus, the application of IL-12 as a mucosal vaccine adjuvant may provide a novel approach for protection against respiratory diseases and could have immediate impact on human health. ..

..The results of this study will provide important insight into the roles of IL-12 and IgA in controlling immunity, and could have immediate impact on human health. ..

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..The results obtained from this study will provide a comprehensive model for understanding microbial interactions in the pulmonary tract and thus provide important insight into the development of effective therapeutics for human use. ..