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TitleSimultaneous priming of HIV broadly neutralizing antibody precursors to multiple epitopes by germline-targeting mRNA-LNP immunogens in mouse models.
Journal, issue, pagesSci Immunol, Vol. 10, Issue 112, Page eadu7961, Year 2025
Publish dateOct 17, 2025
AuthorsZhenfei Xie / Xuesong Wang / Yu Yan / Jon M Steichen / Krystal M Ma / Christopher A Cottrell / Eleonora Melzi / Maria Bottermann / Paula Maldonado Villavicencio / Kimmo Rantalainen / Torben Schiffner / John E Warner / Stephanie R Weldon / Thavaleak Prum / Jordan R Ellis-Pugh / Jonathan L Torres / Abigail M Jackson / Claudia T Flynn / Gabriel Ozorowski / Sunny Himansu / Andrea Carfi / Andrew B Ward / Usha Nair / William R Schief / Facundo D Batista /
PubMed AbstractGermline-targeting is a promising approach to HIV vaccine development that begins with the elicitation of precursors to broadly neutralizing antibodies (bnAbs), but it remains unclear whether ...Germline-targeting is a promising approach to HIV vaccine development that begins with the elicitation of precursors to broadly neutralizing antibodies (bnAbs), but it remains unclear whether simultaneous elicitation of precursors to multiple epitopes on the HIV envelope (Env) would be inhibited by competition. This study used preclinical mouse models with physiologically relevant frequencies of bnAb precursor-bearing B cells to compare precursor elicitation by coadministration of multiple protein or mRNA lipid nanoparticle (mRNA-LNP) germline-targeting immunogens. These immunogens activate multiple bnAb precursor classes targeting distinct epitopes on Env but with evidence of potential competition. Simultaneous delivery of immunogens encoded by mRNA-LNPs, however, drove maturation across different precursor frequencies and immunogen doses. Furthermore, administration of a cocktail of mRNA-LNP immunogens (N332-GT5 gp151, ApexGT5 gp151, eOD-GT8 60mer, and 10E8-GT12 24mer) led to balanced activation of four distinct bnAb precursor classes, indicating that multiepitope HIV bnAb precursor priming might be successfully implemented in humans but might be immunogen dependent.
External linksSci Immunol / PubMed:41105753
MethodsEM (single particle)
Resolution28.0 - 30.0 Å
Structure data

EMDB-70190: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies (V3-glycan epitope) following mRNA multi antigen prime
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-70192: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies (V3-glycan and gp41-base epitopes) following protein multi antigen prime
Method: EM (single particle) / Resolution: 28.0 Å

Source
  • Mus musculus (house mouse)

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