IMMUNIZATION ACTIVATES TRANSIENT SIV VIRAL REPLICATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4+ T cell responses to many common pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected ART treated subjects results in poor HIV-specific responses. In this study, we used a macaque model of HIV-infected individuals treated with ART during chronic infection to study the consequences of SIV antigen stimulation in lymph nodes early after immunization. CMV seropositive Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and CMV pp65 antigen immunization in draining lymph nodes and peripheral blood was analyzed. Animals were immunized with SIV gag encoding plasmid on one side and CMV pp65 encoding plasmid on the contralateral side, which allowed draining lymph nodes for each antigen to be obtained at the same time from the same animal for direct comparison. We observed that both SIV and CMV antigen immunizations stimulated immune activation and transient antigen-specific T cell responses in inpsilateral lymph nodes. The CMV-specific responses were potent and sustained in the periphery for 50 days post-immunization, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation induced transient SIV viral replication in the draining lymph nodes. We hypothesize that viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses, suggesting a mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals.