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In HIV type 1 (HIV-1) infection, virus-specific B-cell and neutralizing antibody (NAb) responses are impaired but exert selective pressure on target viral Envelope (Env) resulting in prominent sequence diversification among geographical areas. The basal induction patterns of HIV Env-specific B cells and their interaction with HIV Env awaits clarification.We investigated the relationship of Env polymorphisms and Env-specific B-cell responses in treatment-naive HIV-1 CRF01_AE-infected Vietnamese.Samples of 43 HIV-1 CRF01_AE infection-identified individuals were divided into acute-phase ( n = 12) and chronic-phase ( n = 31) by combined criteria of serological recent-infection assay and clinical parameters. We quantified subcloning-based polymorphic residue site numbers in plasma-derived Env variable region 1-5 (V1-V5)-coding regions within each individual, designating their summation within each region as variant index. Peripheral blood Env gp 140-specific B-cell responses and plasma neutralizing activity of Env pseudoviruses were examined to analyze their relationship with variant index.HIV-1 CRF01_AE Env gp140-specific total B-cell and plasma cell (CD19 + IgD - CD27 + CD38 + CD138 + ) responses were determined. In chronic-phase samples, significant correlation of variant index in all Env V1-V5 regions with Env-specific plasma cell responses was shown, and V1-V5 total variant index correlated stronger with Env-specific plasma cell as compared with total Env-specific B-cell responses. Env V5 variant index was significantly higher in chronic-phase cross-neutralizers of V5-polymorphic/VRC01-insensitive CRF01_AE Env.Results revealed the association between circulating Env-specific plasma cell responses and Env polymorphisms, implicating selective pressure on Env by plasma cell-derived antibodies and conversely suggests that Env-specific B-cell induction alone is insufficient for exerting Env selective pressure in HIV infection.

Objective Analysis of the quantity and quality of epitope-specific CD8+ T-cell responses is crucial for understanding the mechanism of HIV/simian immunodeficiency virus (SIV) replication control. We have previously shown that acute-phase passive infusion of neutralizing antibodies (NAbs) results in augmented broad T-cell responses and robust SIVmac239 control in rhesus macaques. Analyzing long-term dynamics of CD8+ T-cell responses in these SIV controllers provides important insights into designing lasting anti-HIV immunity. Design We analyzed dynamics and metabolic/functional profiles of SIV-specific CD8+ T-cell responses in rhesus macaques that controlled SIVmac239 replication following acute-phase passive NAb infusion. Methods SIV epitope-specific CD8+ T-cell responses in peripheral blood at multiple chronic-phase time points were investigated in four passive NAb-infused SIV controllers. In particular, expression patterns of Eomesodermin (Eomes), phosphorylated AMP kinase (pAMPK), CD28 and programmed death-1 (PD-1) were examined. Results In the NAb-infused SIV controllers, a single epitope-specific CD8+ T-cell response detected from acute infection and maintaining low levels up to year 1 showed a surge thereafter, up to year 2 post-challenge. Retention of an effector-skewed and unexhausted Eomes-high/pAMPK-low/CD28-negative/PD-1-low subpopulation in these epitope-specific CD8+ T cells implicated their front-line commitment in residual viral replication control. Conclusions In long-term SIV control following acute-phase passive NAb infusion, a single-epitope, high-quality CTL response was dominantly induced in the chronic phase. These results likely describe one favorable pattern of immunodominant epitope-specific CD8+ T-cell preservation and suggest the importance of incorporating metabolic marker signatures for understanding NAb/T-cell synergism-based HIV/SIV control.