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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.

SUBMITTER: Xu K 

PROVIDER: S-EPMC6358635 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Xu Kai K   Acharya Priyamvada P   Kong Rui R   Cheng Cheng C   Chuang Gwo-Yu GY   Liu Kevin K   Louder Mark K MK   O'Dell Sijy S   Rawi Reda R   Sastry Mallika M   Shen Chen-Hsiang CH   Zhang Baoshan B   Zhou Tongqing T   Asokan Mangaiarkarasi M   Bailer Robert T RT   Chambers Michael M   Chen Xuejun X   Choi Chang W CW   Dandey Venkata P VP   Doria-Rose Nicole A NA   Druz Aliaksandr A   Eng Edward T ET   Farney S Katie SK   Foulds Kathryn E KE   Geng Hui H   Georgiev Ivelin S IS   Gorman Jason J   Hill Kurt R KR   Jafari Alexander J AJ   Kwon Young D YD   Lai Yen-Ting YT   Lemmin Thomas T   McKee Krisha K   Ohr Tiffany Y TY   Ou Li L   Peng Dongjun D   Rowshan Ariana P AP   Sheng Zizhang Z   Todd John-Paul JP   Tsybovsky Yaroslav Y   Viox Elise G EG   Wang Yiran Y   Wei Hui H   Yang Yongping Y   Zhou Amy F AF   Chen Rui R   Yang Lu L   Scorpio Diana G DG   McDermott Adrian B AB   Shapiro Lawrence L   Carragher Bridget B   Potter Clinton S CS   Mascola John R JR   Kwong Peter D PD  

Nature medicine 20180604 6


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, the  ...[more]

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