Quadrivalent influenza nanoparticle vaccines induce broad protection

Boyoglu-Barnum, Seyhan; Ellis, Daniel; Gillespie, Rebecca A.; Hutchinson, Geoffrey B.; Park, Young-Jun; Moin, Syed M.; Acton, Oliver J.; Ravichandran, Rashmi; Murphy, Mike; Pettie, Deleah; Matheson, Nick; Carter, Lauren; Creanga, Adrian; Watson, Michael J.; Kephart, Sally; Ataca, Sila; Vaile, John R.; Ueda, George; Crank, Michelle C.; Stewart, Lance; Lee, Kelly K.; Guttman, Miklos; Baker, David; Mascola, John R.; Veesler, David; Graham, Barney S.; King, Neil P.; Kanekiyo, Masaru

Influenza vaccines that confer broad and durable protection against diverse virus strains would have a major impact on global health(1). Here we show that computationally designed, two-component nanoparticle immunogens(2) induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens display 20 hemagglutinin (HA) trimers in an ordered array, and their assembly in vitro enables precisely controlled co-display of multiple distinct HAs in defined ratios. Nanoparticle immunogens co-displaying the four HAs of licensed quadrivalent influenza vaccines (QIV) elicited antibody responses against vaccine-matched strains that were equivalent or superior to commercial QIV, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved HA stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens make them attractive candidates for a supraseasonal influenza vaccine candidates with potential to replace conventional seasonal vaccines(3).