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

Publication ,  Journal Article
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 ...
Published in: Cell Rep
March 15, 2022

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

March 15, 2022

Volume

38

Issue

11

Start / End Page

110514

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • RNA, Messenger
  • Nanoparticles
  • Mice
  • Liposomes
  • Humans
  • HIV-1
  • HIV Antibodies
  • Ferritins
  • Epitopes
 

Citation

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Mu, Z., Wiehe, K., Saunders, K. O., Henderson, R., Cain, D. W., Parks, R., … Haynes, B. F. (2022). mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice. Cell Rep, 38(11), 110514. https://doi.org/10.1016/j.celrep.2022.110514
Mu, Zekun, Kevin Wiehe, Kevin O. Saunders, Rory Henderson, Derek W. Cain, Robert Parks, Diana Martik, et al. “mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.Cell Rep 38, no. 11 (March 15, 2022): 110514. https://doi.org/10.1016/j.celrep.2022.110514.
Mu Z, Wiehe K, Saunders KO, Henderson R, Cain DW, Parks R, et al. mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice. Cell Rep. 2022 Mar 15;38(11):110514.
Mu, Zekun, et al. “mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.Cell Rep, vol. 38, no. 11, Mar. 2022, p. 110514. Pubmed, doi:10.1016/j.celrep.2022.110514.
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. mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice. Cell Rep. 2022 Mar 15;38(11):110514.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

March 15, 2022

Volume

38

Issue

11

Start / End Page

110514

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • RNA, Messenger
  • Nanoparticles
  • Mice
  • Liposomes
  • Humans
  • HIV-1
  • HIV Antibodies
  • Ferritins
  • Epitopes