Nature communicationsNov 25, 2025

Intravaginal delivery of mRNA-made antibodies with improved strength and range for SHIV/HIV protection

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Intravaginal mRNA delivery of engineered bnAb combinations may improve local SHIV/HIV neutralization breadth and potency.

Evidence

This preclinical platform study tested single-chain mRNA-encoded in vitro and in rhesus macaque vaginal explants, where co-expressed PGT121 and VRC07 IgM-like multimers restored neutralization of several strains at < 100 ng/mL and protected explants against multiple ex vivo SHIV challenges.

Caveat

Protection was shown in vitro and in ex vivo macaque vaginal explants, not in live-animal or human HIV acquisition studies.

Simplified

Broadly neutralizing antibodies () prevent HIV infection but face administration and cost challenges. We present single-chain mRNA-encoded bnAbs that improve heavy-light chain assembly and enable three enhancement approaches: co-expression, isotype selection, and engineered nanobodies. We observe enhanced in vitro neutralization through co-expression of PGT121 and VRC07 (targeting V3-glycan and CD4-binding site, respectively) and by replacing IgG constant heavy chain (IgG-C) with IgA-Cor incorporating an IgM tailpiece into IgG-C. While IgG versions fail to neutralize several SHIV/HIV strains, co-expressing PGT121 and VRC07 as IgM-like multimers restores neutralizing capability ( < 100 ng/mL) and substantially improves breadth. Vaginal explants from rhesus macaques, treated with intravaginal aerosolized mRNAs, show robust protection against ex vivo challenges with multiple SHIV strains when PGT121 and VRC07 are co-expressed as IgM-like multimers. Our data present novel drug compositions for intravaginal mRNA delivery to prevent HIV acquisition and advance antibody-design strategies that enhance breadth and potency of existing bnAbs. H H H50

Key numbers

2-log

Decrease in

Comparison of PGT121 aIgG and PGT121 against -C109.

near-complete

Complete protection

Protection achieved in ex vivo macaque vaginal explants with IgM-like multimers.

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Funding

Competing interests

0%of authors

0 of 12

authors report competing interests

12 report none

PubMed

Intravaginal delivery of mRNA-made antibodies with improved strength and range for SHIV/HIV protection

Abstract

Key numbers

Full Text

Funding

Competing interests

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