Faculty, Staff and Student Publications
Publication Date
5-31-2023
Journal
Journal of Virology
Abstract
While neutralizing antibodies that target the HIV-1 fusion peptide have been elicited in mice by vaccination, antibodies reported thus far have been from only a single antibody class that could neutralize ~30% of HIV-1 strains. To explore the ability of the murine immune system to generate cross-clade neutralizing antibodies and to investigate how higher breadth and potency might be achieved, we tested 17 prime-boost regimens that utilized diverse fusion peptide-carrier conjugates and HIV-1 envelope trimers with different fusion peptides. We observed priming in mice with fusion peptide-carrier conjugates of variable peptide length to elicit higher neutralizing responses, a result we confirmed in guinea pigs. From vaccinated mice, we isolated 21 antibodies, belonging to 4 distinct classes of fusion peptide-directed antibodies capable of cross-clade neutralization. Top antibodies from each class collectively neutralized over 50% of a 208-strain panel. Structural analyses - both X-ray and cryo-EM - revealed each antibody class to recognize a distinct conformation of fusion peptide and to have a binding pocket capable of accommodating diverse fusion peptides. Murine vaccinations can thus elicit diverse neutralizing antibodies, and altering peptide length during prime can improve the elicitation of cross-clade responses targeting the fusion peptide site of HIV-1 vulnerability.
Keywords
Animals, Guinea Pigs, Mice, HIV Antibodies, Immunoglobulin Isotypes, Vaccination, Peptides, HIV Seropositivity, Antibodies, Neutralizing, AIDS Vaccines, Broadly Neutralizing Antibodies, HIV-1, env Gene Products, Human Immunodeficiency Virus, HIV Infections
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Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
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Associated Data
PMID: 37098956