IMPORTANCE OF ANTIGEN SPECIFIC IGA RESPONSES IN CONTROLLING SIV/SHIV INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies of virus specific immune responses in HIV exposed and infected individuals as well as SIV vaccine studies in monkeys suggest that it is unlikely that vaccine approaches that stimulate a single arm of the immune system will provide effective protection from viral infection. Several studies have shown that strong CD8+ cytotoxic T lymphocytes (CTL) responses may be elicited by infection or vaccine candidates, which may correlate with marginal decreases in viral loads, yet these do not correlate with protection from infection or disease progression. However, In addition to CTL, B-lymphocytes also play an important role in the immune response to infection by secreting neutralizing and non-neutralizing antibodies to combat invading pathogens. In addition, several new findings suggest SIV-specific IgA responses in mucosal and peripheral immune compartments are important in controlling viral infection. Recent reports have also shown that the specificity and quantitative properties of antibody binding to antigen plays an important role in determining the neutralizing activity of the antibody. Thus we hypothesize that differences in the quality of antigen specific immunoglobulin (Ig) responses will be observed in animals in which viral loads are reduced or undetectable compared to animals that have persistent viremia and progress to AIDS. We also hypothesize that the level of antigen-antibody binding properties and antigen-specific effector memory B cells in tissues or secretory Ig will correlate with the reduction of viral load or disease progression in SIV infected macaques. In the proposed studies, we will examine and compare SIV-specific IgA, IgG and IgM immune responses and antibody binding properties in peripheral blood, and mucosal secretions of macaques inoculated with SIVmac251 and/or SHIVsf162p3. We will also examine the effector function of memory B cells in peripheral blood, broncho-alveolar lavage, bone marrow, small intestine and lymph node tissues from SIV infected macaques.