mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.

Journal Article (Journal Article)

The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alone for priming of broadly neutralizing antibody (bnAb) B cell lineages. The successful expression of complex multivalent nanoparticle immunogens with mRNAs has not been demonstrated. Here, we show that mRNAs can encode antigenic Env trimers on ferritin nanoparticles that initiate bnAb precursor B cell expansion and induce serum autologous tier 2 neutralizing activity in bnAb precursor VH + VL knock-in mice. Next-generation sequencing demonstrates acquisition of critical mutations, and monoclonal antibodies that neutralize heterologous HIV-1 isolates are isolated. Thus, mRNA-LNP can encode complex immunogens and may be of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development.

Full Text

Duke Authors

Cited Authors

  • Mu, Z; Wiehe, K; Saunders, KO; Henderson, R; Cain, DW; Parks, R; Martik, D; Mansouri, K; Edwards, RJ; Newman, A; Lu, X; Xia, S-M; Eaton, A; Bonsignori, M; Montefiori, D; Han, Q; Venkatayogi, S; Evangelous, T; Wang, Y; Rountree, W; Korber, B; Wagh, K; Tam, Y; Barbosa, C; Alam, SM; Williams, WB; Tian, M; Alt, FW; Pardi, N; Weissman, D; Haynes, BF

Published Date

  • March 15, 2022

Published In

Volume / Issue

  • 38 / 11

Start / End Page

  • 110514 -

PubMed ID

  • 35294883

Pubmed Central ID

  • PMC8922439

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2022.110514


  • eng

Conference Location

  • United States