tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 Nov 8;119(45):e2206333119.
doi: 10.1073/pnas.2206333119. Epub 2022 Nov 2.
Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses
Meagan McMahon[SUP] 1 [/SUP], George O'Dell[SUP] 1 [/SUP], Jessica Tan[SUP] 1 2 [/SUP], András Sárközy[SUP] 3 [/SUP], Máté Vadovics[SUP] 3 [/SUP], Juan Manuel Carreño[SUP] 1 [/SUP], Eduard Puente-Massaguer[SUP] 1 [/SUP], Hiromi Muramatsu[SUP] 3 [/SUP], Csaba Bajusz[SUP] 3 4 [/SUP], Willemijn Rijnink[SUP] 1 [/SUP], Mitchell Beattie[SUP] 5 [/SUP], Ying K Tam[SUP] 5 [/SUP], Ericka Kirkpatrick Roubidoux[SUP] 1 2 [/SUP], Isabel Francisco[SUP] 1 [/SUP], Shirin Strohmeier[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 6 [/SUP], Barney S Graham[SUP] 6 [/SUP], Florian Krammer[SUP] 1 7 [/SUP], Norbert Pardi[SUP] 3 [/SUP]
Affiliations
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.
Keywords: T cells; influenza virus; lipid nanoparticle; mRNA vaccine; nucleoside modification.
. 2022 Nov 8;119(45):e2206333119.
doi: 10.1073/pnas.2206333119. Epub 2022 Nov 2.
Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses
Meagan McMahon[SUP] 1 [/SUP], George O'Dell[SUP] 1 [/SUP], Jessica Tan[SUP] 1 2 [/SUP], András Sárközy[SUP] 3 [/SUP], Máté Vadovics[SUP] 3 [/SUP], Juan Manuel Carreño[SUP] 1 [/SUP], Eduard Puente-Massaguer[SUP] 1 [/SUP], Hiromi Muramatsu[SUP] 3 [/SUP], Csaba Bajusz[SUP] 3 4 [/SUP], Willemijn Rijnink[SUP] 1 [/SUP], Mitchell Beattie[SUP] 5 [/SUP], Ying K Tam[SUP] 5 [/SUP], Ericka Kirkpatrick Roubidoux[SUP] 1 2 [/SUP], Isabel Francisco[SUP] 1 [/SUP], Shirin Strohmeier[SUP] 1 [/SUP], Masaru Kanekiyo[SUP] 6 [/SUP], Barney S Graham[SUP] 6 [/SUP], Florian Krammer[SUP] 1 7 [/SUP], Norbert Pardi[SUP] 3 [/SUP]
Affiliations
- PMID: 36322769
- DOI: 10.1073/pnas.2206333119
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.
Keywords: T cells; influenza virus; lipid nanoparticle; mRNA vaccine; nucleoside modification.