Abstract
Although it is now possible to produce recombinant HIV envelope glycoproteins (Envs) with epitopes recognized by the 5–6 major classes of broadly neutralizing antibodies (bNAbs), these have failed to consistently stimulate the formation of bNAbs in immunized animals or humans. In an effort to identify new immunogens better able to elicit bNAbs, we are studying Envs derived from rare individuals who possess bNAbs and are able to control their infection without the need for anti-retroviral drugs (elite supressors or ES), hypothesizing that in at least some people the antibodies may mediate durable virus control. Because virus evolution in people with the ES only phenotype was reported to be limited, we reasoned the Env proteins recovered from these individuals may more closely resemble the Envs that gave rise to bNAbs compared to the highly diverse viruses isolated from normal progressors. Using a phenotypic assay, we screened 25 controllers and identified two for more detailed investigation. In this study, we examined 20 clade B proviral sequences isolated from an African American woman, who had the rare bNAb/ES phenotype. Phylogenetic analysis of proviral envelope sequences demonstrated low genetic diversity. Envelope proteins were unusual in that most possessed two extra cysteines within an elongated V1 region. In this report, we examine the impact of the extra cysteines on the binding to bNAbs, virus infectivity, and sensitivity to neutralization. These data suggest structural motifs in V1 can affect infectivity, and that rare viruses may be prevented from developing escape.
Highlights
Despite the widespread availability of anti-retroviral drugs, recent studies suggest that an HIV vaccine will still be required to control and eliminate the spread of this virus [1, 2]
Twenty-nine plasma specimens from anti-retroviral therapy (ART)-naïve individuals were obtained from the SCOPE Study cohort (University of California, San Francisco) and screened for neutralization breadth with a panel of 22 international virus isolates from five different genetic clades (Supplementary Table 1)
Twenty-five of the plasma specimens were from individuals previously identified as elite supressors (ESs) and four specimens were from normal progressors
Summary
Despite the widespread availability of anti-retroviral drugs, recent studies suggest that an HIV vaccine will still be required to control and eliminate the spread of this virus [1, 2]. A third approach considers the possibility that Envs recovered from rare individuals with high levels of bNAbs, termed elite neutralizers (ENs), may be more effective in eliciting bNAbs than Envs from normal progressors that failed to produce bNAbs. the task of antigen selection from ENs is complicated by the fact that bNAbs are typically detected 2 years or more after infection [39, 40]. The task of antigen selection from ENs is complicated by the fact that bNAbs are typically detected 2 years or more after infection [39, 40] By this time, Env sequences have diversified considerably and most circulating plasma viruses are enriched for neutralization resistant variants [41, 42]. Finding the precursor envelope sequences likely to have elicited bNAbs in an EN is a formidable challenge
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
