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Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates

By Kevin O Saunders, Norbert Pardi, Robert Parks, Sampa Santra, Zekun Mu, Laura Sutherland, Richard Scearce, Maggie Barr, Amanda Eaton, Giovanna Hernandez, Derrick Goodman, Michael J. Hogan, Istvan Tombacz, David N. Gordon, R. Wes Rountree, Yunfei Wang, Mark G Lewis, Theodore C. Pierson, Chris Barbosa, Ying Tam, Xiaoying Shen, Guido Ferrari, Georgia D. Tomaras, David C. Montefiori, Drew Weissman, Barton F Haynes

Posted 31 Dec 2020
bioRxiv DOI: 10.1101/2020.12.30.424745

Development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we found that mRNA-LNP immunization compared to protein immunization elicited either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope (prM-E) or HIV-1 Env gp160 induced durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 g were immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.

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