Sequential exposure to specific antibody escape mutations may program neutralization breadth during subtype A HIV-1 infection

Mk Murphy,S Boliar,S Gnanakaran,R Pan,A Sethi,E Hunter,L Yue,E Karita,X Kong,Je Robinson,E Cormier,Ca Derdeyn,Sa Allen

doi:10.1186/1742-4690-9-s2-p104

Abstract

Methods Here we characterized the initial nAb response in a subtype A HIV-1-infected Rwandan seroconverter and investigated how consequent immune events influenced the downstream development of cross-clade breadth. Autologous envelope (Env) glycoproteins from the transmitted/ founder virus and twenty longitudinal nAb escape variants were utilized to define the neutralization targets of autologous plasma and monoclonal antibodies (mAbs), the latter of which were also examined genetically and structurally through crystallization. Heterologous Env glycoproteins from nine cross-clade variants were used to determine neutralization breadth.

Highlights

Mechanisms that expand the otherwise narrow neutralization capacity observed during early HIV-1 infection are currently undefined, but multiple lines of evidence suggest that the ability to elicit broad and potent neutralizing antibodies via vaccination could increase the protective efficacy of immunization
Subsequent monoclonal antibodies (mAbs) resistance arose in later Envs through alteration of two glycan motifs previously implicated in the development of neutralizing antibodies (nAbs) breadth
Initially, nAbs targeted a single region of gp120 at the base of V3 involving the alpha2 helix

Summary

Background

Mechanisms that expand the otherwise narrow neutralization capacity observed during early HIV-1 infection are currently undefined, but multiple lines of evidence suggest that the ability to elicit broad and potent neutralizing antibodies (nAbs) via vaccination could increase the protective efficacy of immunization. Subsequent mAb resistance arose in later Envs through alteration of two glycan motifs previously implicated in the development of nAb breadth. Three-year autologous plasma displayed moderate neutralization breadth and most potently neutralized heterologous Envs containing the altered glycan motifs

Methods

Results

Conclusion