Journal
NATURE MEDICINE
Volume 24, Issue 6, Pages 857-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-018-0042-6
Keywords
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Funding
- Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- IAVI's NAC
- federal funds from the Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E]
- NIH [R01 AI131722, OD019994]
- Simons Foundation NYSTAR [SF349247]
- NIH National Institute of General Medical Sciences [GM103310]
- Agouron Institute [F00316]
- US Department of Energy, Basic Energy Sciences, Office of Science, [W-31-109-Eng-38]
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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.
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