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

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 () and Philip J. Santangelo ()
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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

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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

Date: 2025
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DOI: 10.1038/s41467-025-65456-x

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