Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design
Индукция широко нейтрализующих антител к ВИЧ двумяэтапным механизмом: выводы для разработки вакцин
2026-05-07
SCID: 54.1/xseygb97
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Env-bNAb coevolutionV1-directed antibody selectionV3-glycan bNAbsbroadly neutralizing antibodiesepitope-focused SHIV.5MUT
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Abstract (AI)
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 envelope (Env) glycoprotein variants 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.
Key Findings
1
An engineered epitope-focused SHIV (SHIV.5MUT) elicited broad and potent V3-glycan-targeted bNAbs within a year in 14 of 22 macaques, versus 0 of 14 controls.
2
Mapping Env–bNAb coevolution identified a diverse repertoire of bNAb precursors and corresponding Env variants, providing a molecular blueprint for vaccine design.
3
Rhesus bNAbs generated were immunogenetically and structurally diverse and closely resembled human V3-glycan bNAbs.
4
SHIV.5MUT induces bNAbs via a two-step mechanism: initial V1-directed antibodies select for shortened, hypoglycosylated V1 Env variants.
5
The selected shortened, hypoglycosylated V1 variants prime V3-glycan bNAb precursors, enabling maturation of broadly neutralizing responses.
Research Object
Epitope-focused simian-human immunodeficiency virus SHIV.5MUT used to elicit broadly neutralizing HIV antibodies in macaques
Research Subject
Two-step mechanism of bNAb induction involving initial V1-directed antibody selection for shortened, hypoglycosylated Env V1 loops that prime V3-glycan broadly neutralizing antibody precursors, and the resulting Env–bNAb coevolution informing vaccine design
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2026-05-07
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