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Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates #MMPMID33837212
Saunders KO; Pardi N; Parks R; Santra S; Mu Z; Sutherland L; Scearce R; Barr M; Eaton A; Hernandez G; Goodman D; Hogan MJ; Tombacz I; Gordon DN; Rountree RW; Wang Y; Lewis MG; Pierson TC; Barbosa C; Tam Y; Matyas GR; Rao M; Beck Z; Shen X; Ferrari G; Tomaras GD; Montefiori DC; Weissman D; Haynes BF
NPJ Vaccines 2021[Apr]; 6 (1): 50 PMID33837212show ga
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 mug 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.