Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Nat. Med. 2018;24(6):857-867 doi: 10.1038/s41591-018-0042-6
- PMID: 29867235
- Title: Epitope based vaccine design yields fusion peptide directed antibodies that neutralize diverse strains of HIV 1
- Abstract: 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.
- Date: 1970-08-22
- Year: 2018
- Journal: Nat. Med.
- PMID Author: Xu K, Acharya P, Kong R, Cheng C, Chuang GY, Liu K, Louder MK, O'Dell S, Rawi R, Sastry M, Shen CH, 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 YT, Lemmin T, McKee K, Ohr TY, Ou L, Peng D, Rowshan AP, Sheng Z, Todd JP, 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
- IAVI Topics: HIV Immunogen Design