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

Author

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  • Jae Yeon Joo

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

  • Peng Xiao

    (University of Louisiana Lafayette, New Iberia Research Center)

  • Susan P. John

    (University of Louisiana Lafayette, New Iberia Research Center)

  • Daryll Vanover

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

  • Hannah E. Peck

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

  • Loren E. Sasser

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

  • Deepanwita Bose

    (University of Louisiana Lafayette, New Iberia Research Center)

  • Younghun Jung

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

  • Jaehyeon Hwang

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

  • Chiara Zurla

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

  • Francois Villinger

    (University of Louisiana Lafayette, New Iberia Research Center)

  • Philip J. Santangelo

    (Georgia Institute of Technology and Emory University, Wallace H. Coulter Department of Biomedical Engineering)

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-CH) with IgA-CH or incorporating an IgM tailpiece into IgG-CH. While IgG versions fail to neutralize several SHIV/HIV strains, co-expressing PGT121 and VRC07 as IgM-like multimers restores neutralizing capability (IC50

Suggested Citation

  • Jae Yeon Joo & Peng Xiao & Susan P. John & Daryll Vanover & Hannah E. Peck & Loren E. Sasser & Deepanwita Bose & Younghun Jung & Jaehyeon Hwang & Chiara Zurla & Francois Villinger & Philip J. Santange, 2025. "Intravaginal delivery of mRNA-encoded antibodies with enhanced breadth and potency for SHIV/HIV protection," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65456-x
    DOI: 10.1038/s41467-025-65456-x
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