Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design
Summary
A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directe
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# Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design
*Published: 2026 May 7*
A major obstacle confronting HIV-1 vaccine and cure research is the lack of an
outbred animal model for rapid and consistent induction of broadly neutralizing
antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency
virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies
within a year of infection in 14 of 22 macaques compared with 0 of 14 control
animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial
wave of V1-directed antibodies that selected for Envs with shortened,
hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors.
Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling
human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of
bNAb precursors and the Env variants that matured them, yielding a molecular
blueprint for vaccine design.
DOI: 10.1126/science.aec6396