Abstract
Reduced risk of HIV-1 infection correlated with antibody responses to the envelope variable 1 and 2 regions in the RV144 vaccine trial. To understand the relationship between antibody responses, V2 sequence, and structure, plasma samples (n = 16) from an early acute HIV-1 infection cohort from Thailand infected with CRF01_AE strain were analyzed for binding to V2 peptides by surface plasmon resonance. Five participants with a range of V2 binding responses at week 24 post-infection were further analyzed against a set of four overlapping V2 peptides that were designed based on envelope single-genome amplification. Antibody responses that were relatively consistent over the four segments of the V2 region or a focused response to the C-strand (residues 165–186) of the V2 region were observed. Viral escape in the V2 region resulted in significantly reduced antibody binding. Structural modeling indicated that the C-strand and the sites of viral variation were highly accessible in the open conformation of the HIV-1 Env trimer. V2 residues, 165–186 are preferentially targeted during acute infection. Residues 169–184 were also preferentially targeted by the protective immune response in the RV144 trial, thus emphasizing the importance of these residues for vaccine design.
Highlights
IntroductionThe RV144 HIV-1 vaccine trial in Thailand demonstrated 31.2% efficacy after 3.5 years [1] and
The RV144 HIV-1 vaccine trial in Thailand demonstrated 31.2% efficacy after 3.5 years [1] and60% efficacy 1 year after vaccination in post hoc analysis [2]
To determine if the V2 region was a target for the induction of antibodies during a primary infection, plasma samples from an early capture acute HIV-1 infection (AHI) prospective study (RV217) were examined
Summary
The RV144 HIV-1 vaccine trial in Thailand demonstrated 31.2% efficacy after 3.5 years [1] and. 60% efficacy 1 year after vaccination in post hoc analysis [2]. Immune correlates analysis of a subset of vaccinees at two weeks post final vaccination revealed that antibodies against the Envelope (Env) variable loop 1 and 2 region (V1V2) were associated with lower risk of infection [3]. Further analysis indicated that binding antibody responses to subtypes A, B, C, and CRF01_AE V1V2 proteins correlated with reduced infection risk [4]. The Env V1V2-region has extensive loop length, glycosylation variation, and major sequence differences both within and between clades [7,8,9,10,11,12,13,14,15]. The V1V2-region is located at the membrane-distal apex of the viral Env spike, and in the closed mature HIV-1 molecule [16,17,18]
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