Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1.

Published

Journal Article

A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. The N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.

Full Text

Duke Authors

Cited Authors

  • Xu, K; Acharya, P; Kong, R; Cheng, C; Chuang, G-Y; Liu, K; Louder, MK; O'Dell, S; Rawi, R; Sastry, M; Shen, C-H; Zhang, B; Zhou, T; Asokan, M; Bailer, RT; Chambers, M; Chen, X; Choi, CW; Dandey, VP; Doria-Rose, NA; Druz, A; Eng, ET; Farney, SK; Foulds, KE; Geng, H; Georgiev, IS; Gorman, J; Hill, KR; Jafari, AJ; Kwon, YD; Lai, Y-T; Lemmin, T; McKee, K; Ohr, TY; Ou, L; Peng, D; Rowshan, AP; Sheng, Z; Todd, J-P; Tsybovsky, Y; Viox, EG; Wang, Y; Wei, H; Yang, Y; Zhou, AF; Chen, R; Yang, L; Scorpio, DG; McDermott, AB; Shapiro, L; Carragher, B; Potter, CS; Mascola, JR; Kwong, PD

Published Date

  • June 2018

Published In

Volume / Issue

  • 24 / 6

Start / End Page

  • 857 - 867

PubMed ID

  • 29867235

Pubmed Central ID

  • 29867235

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/s41591-018-0042-6

Language

  • eng

Conference Location

  • United States