标题: Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV [打印本页] 作者: wwwkkk83 时间: 2019-7-26 11:04 标题: Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV Highlights
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Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV
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Development for five NHP lineages of vaccine-induced broadly neutralizing antibodies
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FP-carrier effective at priming and Env-trimer effective at maturing
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Priming with a target subregion induces antibodies with target-interaction hotspots
Summary
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization