HIV-Specific CD4 T Cell Responses to Different Viral Proteins Have Discordant Associations with Viral Load and Clinical Outcome

摘要: A successful prophylactic vaccine is characterized by long-lived immunity, which critically dependent on CD4 T cell-mediated helper signals. Indeed, most licensed vaccines induce antigen-specific cell responses, in addition to high-affinity antibodies. However, despite the important role of cells design and natural infection, few studies have HIV-specific due their preferential susceptibility HIV infection. To establish at population level impact viral control define specificity peptide targeting, we conducted a comprehensive analysis these responses entire proteome 93 subjects different stages We show that were detectable 92% individuals breadth showed significant inverse correlation with load (P = 0.009, R -0.31). In particular, targeting Gag robustly associated lower levels viremia 0.0002, -0.45). Importantly, differences immunodominance profile distinguished controllers from progressors. Furthermore, Gag/Env ratios potent marker control, high frequency magnitude low proportion Env effective immune control. At epitope level, three distinct peptides was linked spontaneous 0.60 0.85). Inclusion immunogenic proteins future may act as critical cornerstone for enhancing protective responses.