Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses
Meagan McMahon, George O’Dell, Jessica Tan, András Sárközy, Máté Vadovics, Juan Manuel Carreño, Eduard Puente‐Massaguer, Hiromi Muramatsu, Csaba Bajusz, Willemijn F. Rijnink, Mitchell Beattie, Ying K. Tam, Ericka Kirkpatrick Roubidoux, Isabel Francisco, Shirin Strohmeier, Masaru Kanekiyo, Barney S. Graham, Florian Krammer, Norbert Pardi
Abstract
Combined vaccine formulations targeting not only hemagglutinin but also other influenza virus antigens could form the basis for a universal influenza virus vaccine that has the potential to elicit long-lasting, broadly cross-reactive immune responses. Lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) vaccines can be utilized to efficiently target multiple antigens with a single vaccine. Here, we assessed the immunogenicity and protective efficacy of nucleoside-modified mRNA-LNP vaccines that contain four influenza A group 2 virus antigens (hemagglutinin stalk, neuraminidase, matrix protein 2, and nucleoprotein) in mice. We found that all vaccine components induced antigen-specific cellular and humoral immune responses after administration of a single dose. While the monovalent formulations were not exclusively protective, the combined quadrivalent formulation protected mice from all challenge viruses, including a relevant H1N1 influenza virus group 1 strain, with minimal weight loss. Importantly, the combined vaccine protected from morbidity at a dose of 125 ng per antigen after a single vaccination in mice. With these findings, we confidently conclude that the nucleoside-modified mRNA-LNP platform can be used to elicit protection against a large panel of influenza viruses.