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

Saunders, K. O.; Pardi, N.; Parks, R.; Santra, S.; Mu, Z.; Sutherland, L. L.; Scearce, R.; Barr, M.; Eaton, A.; Hernandez, G.; Goodman, D.; Hogan, M. J.; Tombacz, I.; Gordon, D.; Rountree, R. W.; Wang, Y.; Lewis, M. G.; Pierson, T.; Barbosa, C.; Tam, Y.; Shen, S.; Ferrari, G.; Tomaras, G. D.; Montefiori, D. C.; Weissman, D.; Haynes, B. F.

doi:10.1101/2020.12.30.424745

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bioRxiv · 10.1101/2020.12.30.424745

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

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Abstract

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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Saunders, K. O., Pardi, N., Parks, R., Santra, S., Mu, Z., Sutherland, L. L., Scearce, R., Barr, M., Eaton, A., Hernandez, G., Goodman, D., Hogan, M. J., Tombacz, I., Gordon, D., Rountree, R. W., Wang, Y., Lewis, M. G., Pierson, T., Barbosa, C., Tam, Y., Shen, S., Ferrari, G., Tomaras, G. D., Montefiori, D. C., Weissman, D., Haynes, B. F.. 2020-12-31. Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates. https://doi.org/10.1101/2020.12.30.424745

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