Abstract
BackgroundMajority of HIV-1 infection is established by one transmitted/founder virus and understanding how the neutralizing antibodies develop against this virus is critical for our rational design an HIV-1 vaccine. ResultsWe report here antibody profiling of sequential plasma samples against transmitted/founder HIV-1 envelope glycoprotein in an epidemiologically linked transmission pair using our previously reported antigen library approach. We have decomposed the antibody recognition into three major subdomains on the envelope and showed their development in vivo followed a spatiotemporal hierarchy: starting with the ectodomain of gp41 at membrane proximal region, then the V3C3V4 and the V1V2 of gp120 at the membrane distal region. While antibodies to these subdomains appeared to undergo avidity maturation, the early anti-gp41 antibodies failed to translate into detectable autologous neutralization. Instead, it was the much delayed anti-V3C3V4 and anti-V1V2 antibodies constituted the major neutralizing activities.ConclusionsOur results indicate that the initial antibody response was severely misguided by the transmitted/founder virus and future vaccine design would need to avoid the ectodomain of gp41 and focus on the neutralizing targets in the V3C3V4 and V1V2 subdomains of gp120.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0243-3) contains supplementary material, which is available to authorized users.
Highlights
Majority of HIV-1 infection is established by one transmitted/founder virus and understanding how the neutralizing antibodies develop against this virus is critical for our rational design an HIV-1 vaccine
Our results indicate that the initial antibody response was severely misguided by the transmitted/founder virus and future vaccine design would need to avoid the ectodomain of gp41 and focus on the neutralizing targets in the V3C3V4 and V1V2 subdomains of gp120
P08 and P11 were identified through a Chinese acute infection cohort for men who have sex with men (MSM) that has been following several thousands of high risk individuals over the last decade
Summary
Majority of HIV-1 infection is established by one transmitted/founder virus and understanding how the neutralizing antibodies develop against this virus is critical for our rational design an HIV-1 vaccine. Neutralizing antibodies are the major component of protective immunity against viral infection in humans. Polyclonal by nature, they exert their function by targeting the crucial antigenic domains on the viral envelop glycoprotein. Studies based on short peptides, chimeric and epitope-specific mutant viruses have identified a few subdomains of gp120 are the major targets for neutralizing activities in polyclonal sera [30,31,32,33]. The detailed understanding on the scope, specificities and dynamic features of polyclonal antibody recognition against the transmitted/founder virus remain elusive
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