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Mu Z, Wiehe K, Saunders KO, et al. Ability of nucleoside-modified mRNA to encode HIV-1 envelope trimer nanoparticles. bioRxiv. 2021;doi: 10.1101/2021.08.09.455714.
Mu, Z., Wiehe, K., Saunders, K. O., Henderson, R., Cain, D. W., Parks, R., Martik, D., Mansouri, K., Edwards, R. J., Newman, A., Lu, X., Xia, S. M., Bonsignori, M., Montefiori, D., Han, Q., Venkatayogi, S., Evangelous, T., Wang, Y., Rountree, W., Tam, Y., Barbosa, C., Munir Alam, S., Williams, W. B., Pardi, N., Weissman, D., & Haynes, B. F. (2021). Ability of nucleoside-modified mRNA to encode HIV-1 envelope trimer nanoparticles. bioRxiv : the preprint server for biology, . https://doi.org/10.1101/2021.08.09.455714
Mu, Zekun, et al. "Ability of nucleoside-modified mRNA to encode HIV-1 envelope trimer nanoparticles." bioRxiv : the preprint server for biology vol. (2021). doi: https://doi.org/10.1101/2021.08.09.455714
Mu Z, Wiehe K, Saunders KO, Henderson R, Cain DW, Parks R, Martik D, Mansouri K, Edwards RJ, Newman A, Lu X, Xia SM, Bonsignori M, Montefiori D, Han Q, Venkatayogi S, Evangelous T, Wang Y, Rountree W, Tam Y, Barbosa C, Munir Alam S, Williams WB, Pardi N, Weissman D, Haynes BF. Ability of nucleoside-modified mRNA to encode HIV-1 envelope trimer nanoparticles. bioRxiv. 2021 Aug 09; doi: 10.1101/2021.08.09.455714. PMID: 34401876; PMCID: PMC8366792.
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bioRxiv. 2021 Aug 09; doi: 10.1101/2021.08.09.455714.

Ability of nucleoside-modified mRNA to encode HIV-1 envelope trimer nanoparticles.

bioRxiv : the preprint server for biology

Zekun Mu, Kevin Wiehe, Kevin O Saunders, Rory Henderson, Derek W Cain, Robert Parks, Diana Martik, Katayoun Mansouri, Robert J Edwards, Amanda Newman, Xiaozhi Lu, Shi-Mao Xia, Mattia Bonsignori, David Montefiori, Qifeng Han, Sravani Venkatayogi, Tyler Evangelous, Yunfei Wang, Wes Rountree, Ying Tam, Christopher Barbosa, S Munir Alam, Wilton B Williams, Norbert Pardi, Drew Weissman, Barton F Haynes

PMID: 34401876 PMCID: PMC8366792 DOI: 10.1101/2021.08.09.455714

Abstract

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 to 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 demonstrated acquisition of critical mutations, and monoclonal antibodies that neutralized heterologous HIV-1 isolates were isolated. Thus, mRNA- LNP can encode complex immunogens and are of use in design of germline-targeting and sequential boosting immunogens for HIV-1 vaccine development.

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