TY - JOUR
T1 - Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses
AU - McMahon, Meagan
AU - O’Dell, George
AU - Tan, Jessica
AU - Sárközy, András
AU - Vadovics, Máté
AU - Carreño, Juan Manuel
AU - Puente-Massaguer, Eduard
AU - Muramatsu, Hiromi
AU - Bajusz, Csaba
AU - Rijnink, Willemijn
AU - Beattie, Mitchell
AU - Tam, Ying K.
AU - Roubidoux, Ericka Kirkpatrick
AU - Francisco, Isabel
AU - Strohmeier, Shirin
AU - Kanekiyo, Masaru
AU - Graham, Barney S.
AU - Krammer, Florian
AU - Pardi, Norbert
N1 - Funding Information:
ACKNOWLEDGMENTS. The study was supported by NIH R01-AI146101 (NP and MM) and by the Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00051 (FK). Cs. B. was a postdoctoral fellow supported by the Biotechnological National Laboratory, Szeged, Hungary. András Sárk€ozy was supported by the Rosztoczy Foundation. The NP and M2 peptides used in the T cell studies were kindly provided by Michael J. Hogan and Laurence C. Eisenlohr (Children’s Hospital of Philadelphia). Figure 3A and Supplemental Figure 4A were created with BioRender.
Funding Information:
The study was supported by NIH R01-AI146101 (NP and MM) and by the Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00051 (FK). Cs. B. was a postdoctoral fellow supported by the Biotechnological National Laboratory, Szeged, Hungary. András Sárközy was supported by the Rosztoczy Foundation. The NP and M2 peptides used in the T cell studies were kindly provided by Michael J. Hogan and Laurence C. Eisenlohr (Children’s Hospital of Philadelphia). Figure 3A and Supplemental Figure 4A were created with BioRender.
Publisher Copyright:
Copyright © 2022 the Author(s).
PY - 2022/11/8
Y1 - 2022/11/8
N2 - 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.
AB - 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.
KW - T cells
KW - influenza virus
KW - lipid nanoparticle
KW - mRNA vaccine
KW - nucleoside modification
UR - http://www.scopus.com/inward/record.url?scp=85141113213&partnerID=8YFLogxK
U2 - 10.1073/pnas.2206333119
DO - 10.1073/pnas.2206333119
M3 - Article
C2 - 36322769
AN - SCOPUS:85141113213
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 45
M1 - e2206333119
ER -