Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. (June 2018)

• Record Type: Journal Article
• Authors: Xu, Kai; Acharya, Priyamvada; Kong, Rui; Cheng, Cheng; Chuang, Gwo-Yu; Liu, Kevin; Louder, Mark; O'Dell, Sijy; Rawi, Reda; Sastry, Mallika; Shen, Chen-Hsiang; Zhang, Baoshan; Zhou, Tongqing; Asokan, Mangaiarkarasi; Bailer, Robert; Chambers, Michael; Chen, Xuejun; Choi, Chang; Dandey, Venkata; Doria-Rose, Nicole; Druz, Aliaksandr; Eng, Edward; Farney, S.; Foulds, Kathryn; Geng, Hui; Georgiev, Ivelin; Gorman, Jason; Hill, Kurt; Jafari, Alexander; Kwon, Young; Lai, Yen-Ting; Lemmin, Thomas; McKee, Krisha; Ohr, Tiffany; Ou, Li; Peng, Dongjun; Rowshan, Ariana; Sheng, Zizhang; Todd, John-Paul; Tsybovsky, Yaroslav; Viox, Elise; Wang, Yiran; Wei, Hui; Yang, Yongping; Zhou, Amy; Chen, Rui; Yang, Lu; Scorpio, Diana; McDermott, Adrian; Shapiro, Lawrence; Carragher, Bridget; Potter, Clinton; Mascola, John; Kwong, Peter;
• Is Part Of: Nature medicine. Volume 24:Number 6(2018)
• Page Start: 857
• Page End: 867
• Publication Date: 2018-06
• Subjects: Pathology, Molecular -- Periodicals; Molecular biology -- Periodicals; 610.724
• DOI: 10.1038/s41591-018-0042-6
• Languages: English
• ISSNs: 1078-8956

Abstract

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. An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.