Broadly Neutralizing Antibodies against HIV: Back to Blood

Abstract

After years of continuous exposure to HIV envelope antigens, a minority of HIV-infected individuals develop a cognate polyclonal humoral response comprising very potent and extremely cross-reactive neutralizing antibodies [broadly neutralizing antibodies (bNAbs)]. Isolated bNAbs derived from memory B cell pools have been the focus of intense studies over the past decade. However, it is not yet known how to translate the features of bNAbs into practical HIV prevention methods. In this review, we attempt to seek insights from emerging information about the human broadly neutralizing plasma response as well as its frequency, clonal composition, specificity, potency, and commonality among infected subjects. We also consider how this information points to selecting and prioritizing certain epitope targets and strategies for HIV vaccine design.

Keywords: HIV; antibody; bNAbs; gp120; neutralization; vaccine.

Figure 1.

Potential uses for HIV-1 bNAbs

Figure 2.

Epitopes targeted by bNAbs on the HIV BG505 trimer. The HIV-1 gp120 is shown in light grey, and HIV-1 gp41 in grey. The glycosylation throughout the trimer (glycan shield) is represented by green residues. The following colors were used for the epitopes: orange (V3-glycan), light blue (V2-glycan), dark blue (CD4bs), yellow (subunit interface), and purple (fusion peptide). Epitope residues for PGT145 (V2-glycan), PGT 121 (V3-glycan), 8ANC19 (subunit interface), and PGT 151 (fusion peptide) obtained from [128], and N49P7 (CD4bs) was obtained from [7].