Although development of an effective AIDS vaccine to provide sterilizing immunity remains an elusive goal, vaccine protection from disease progression has been achieved in animal models, supporting this approach as a realistic goal for first generation vaccines for humans. Expanding evidence indicates that events in the acute stage of infection determine long-term outcome, and that HIV-specific CD8 T cells are critical for containment of viral replication. Major challenges persist, including the tremendous HIV diversity among strains, and that the relative contributions of individual responses to immune containment in acute infection and over the course of disease are not known. This is now an even more critical issue given the failure of a recent phase lib study of a CTL based vaccine, which was recently shown to be ineffective in influencing viral set point after infection, despite the induction of strong CDS T cell responses by IFN-y Elispot. During the past funding period, we have worked closely with each of the other PLs on this PO1 to generate preliminary data indicating that only a subset of HLA alleles and epitopes participate in the acute phase CD8 T cell response; that antigen processing contributes to immunodominance by favoring the production of certain epitopes over others; that some anti-HIV responses contribute to immune containment, whereas others act as

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Massachusetts General Hospital
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Scully, Eileen P; Lockhart, Ainsley; Garcia-Beltran, Wilfredo et al. (2016) Innate immune reconstitution with suppression of HIV-1. JCI Insight 1:e85433
Palmer, Christine D; Romero-Tejeda, Marisol; Sirignano, Michael et al. (2016) Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation. J Immunol 196:668-77
Scully, Eileen; Lockhart, Ainsley; Huang, Lisa et al. (2016) Elevated Levels of Microbial Translocation Markers and CCL2 Among Older HIV-1-Infected Men. J Infect Dis 213:771-5
Carlson, Jonathan M; Du, Victor Y; Pfeifer, Nico et al. (2016) Impact of pre-adapted HIV transmission. Nat Med 22:606-13
Sun, Hong; Kim, Dhohyung; Li, Xiaodong et al. (2015) Th1/17 Polarization of CD4 T Cells Supports HIV-1 Persistence during Antiretroviral Therapy. J Virol 89:11284-93
Martins, Mauricio A; Tully, Damien C; Cruz, Michael A et al. (2015) Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8+ T-Cell Responses Focused on a Single Nef Epitope Select for Escape Variants Shortly after Infection. J Virol 89:10802-20
Carlson, Jonathan M; Schaefer, Malinda; Monaco, Daniela C et al. (2014) HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science 345:1254031
Vaidya, Sagar A; Korner, Christian; Sirignano, Michael N et al. (2014) Tumor necrosis factor α is associated with viral control and early disease progression in patients with HIV type 1 infection. J Infect Dis 210:1042-6
Körner, Christian; Granoff, Mitchell E; Amero, Molly A et al. (2014) Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes. Eur J Immunol 44:2938-48
Foley, Maria Hottelet; Forcier, Talitha; McAndrew, Elizabeth et al. (2014) High avidity CD8+ T cells efficiently eliminate motile HIV-infected targets and execute a locally focused program of anti-viral function. PLoS One 9:e87873

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