Intravaginal delivery of mRNA-encoded antibodies with enhanced breadth and potency for SHIV/HIV protection.

ABSTRACT: Broadly neutralizing antibodies (bnAbs) 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_H) with IgA-C_H or incorporating an IgM tailpiece into IgG-C_H. While IgG versions fail to neutralize several SHIV/HIV strains, co-expressing PGT121 and VRC07 as IgM-like multimers restores neutralizing capability (IC₅₀ < 100 ng/mL) and substantially improves breadth. Vagina

SUBMITTER: Joo JY 

PROVIDER: S-EPMC12647688 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature