Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1.
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.
Duke Scholars
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- env Gene Products, Human Immunodeficiency Virus
- Recombinant Fusion Proteins
- Peptides
- Neutralization Tests
- Models, Molecular
- Mice, Inbred C57BL
- Macaca mulatta
- Immunology
- Immunization
- HIV-1
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- env Gene Products, Human Immunodeficiency Virus
- Recombinant Fusion Proteins
- Peptides
- Neutralization Tests
- Models, Molecular
- Mice, Inbred C57BL
- Macaca mulatta
- Immunology
- Immunization
- HIV-1