Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates
Kevin O. Saunders, Norbert Pardi, Robert Parks, Sampa Santra, Zekun Mu, Laura L. Sutherland, Richard M. Scearce, Maggie Barr, Amanda Eaton, Giovanna E. Hernandez, Derrick Goodman, Michael J. Hogan, István Tombácz, David Gordon, Wes Rountree, Yunfei Wang, Mark G. Lewis, Theodore C. Pierson, Chris Barbosa, Ying K. Tam, Gary R. Matyas, Mangala Rao, Zoltán Beck, Xiaoying Shen, Guido Ferrari, Georgia D. Tomaras, David C. Montefiori, Drew Weissman, Barton F. Haynes
Abstract
The 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 show that mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope or HIV-1 Env gp160 induces durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 μg are 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.