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This research symposium focuses on developing and standardizing serologic tools, assessing immune correlates of protection, and evaluating flu vaccine immunity for pandemic preparedness.
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John R. LaMontagne Memorial Symposiumon Pandemic Influenza ResearchApril 4-5, 2005Institute of Medicine Working Group Five: Immunology, Assay Standardization, and Correlates of Protection Research Recommendations
Develop, validate and standardize serologic tools for pandemic preparedness (1-2 yr) • Improve neutralization assays for avian strains: Standard protocols, engineered inoculum (BSL-2), automation • Improve HAI for detection of H5 antibodies • Develop ELISA methods for HA subtypes • Develop standardized purified/recombinant HA and NA proteins and reference serum panels • Develop and standardize assays for anti-NA • Correlate subtype ELISA with ‘gold standard functional’ inhibition (NI) method
Seroepidemiologic research related to pandemic preparedness • Assess pre-pandemic antibodies to HA and NA • Investigate potential cross-protection provided by human anti-HA or anti-NA against avian strains • Longer term goal: • Simpler serologic assays for field use
Investigate immune correlates of protection Goal: Characterize the human immune response to flu infection and vaccines using modern immunologic techniques Examples • Subtype-specific ELISA and neutralization assays for HA and NA to improve understanding of protection and cross-protection • Role of IgG/IgA in serum or at mucosal sites with specificity for HA or NA in protection • Use new methods for probing human immune responses to primary and secondary flu infection with non-pandemic strains in order to develop methods that can be applied immediately to studies in a pandemic setting • Characteristics of flu-specific memory T cells and B cells • Trafficking of immune cells to lung, mucosa, etc. • Cross-protective immunity by T cells against flu proteins
Apply new immunologic assays in prospective studies using clinical endpoints + viral shedding to define correlates of protection • Improve understanding of consequences of antigenic ‘drift’ in H5 strains • Use new tools to better understand immunopathogenesis in complex/fatal flu infection (epidemic and pandemic cases)
Additional research to evaluate flu vaccine immunity (2-5 yr) Goal: Develop panel of standardized immunologic assays for use in designing pandemic vaccines • Compare capacities of inactivated, live attenuated and vectored vaccines to induce humoral, cellular and mucosal immunity, with primary and secondary vaccination and with varying routes of administration • Immunogenicity and efficacy in infants, children, adults and the elderly • Time to induction of protective response • Persistence of immune response • Generate experience with multiple pandemic vaccines to assess reactogenicity, immunogenicity, optimal dose and route of administration