mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020
BackgroundThe implementation of mRNA vaccines against COVID-19 has successfully validated the safety and efficacy of the platform, while at the same time revealing the potential for their applications against other infectious diseases. Traditional seasonal influenza vaccines often induce strain spec...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1334670/full |
| _version_ | 1797265530004963328 |
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| author | James D. Allen James D. Allen James D. Allen Ted M. Ross Ted M. Ross Ted M. Ross Ted M. Ross |
| author_facet | James D. Allen James D. Allen James D. Allen Ted M. Ross Ted M. Ross Ted M. Ross Ted M. Ross |
| author_sort | James D. Allen |
| collection | DOAJ |
| description | BackgroundThe implementation of mRNA vaccines against COVID-19 has successfully validated the safety and efficacy of the platform, while at the same time revealing the potential for their applications against other infectious diseases. Traditional seasonal influenza vaccines often induce strain specific antibody responses that offer limited protection against antigenically drifted viruses, leading to reduced vaccine efficacy. Modern advances in viral surveillance and sequencing have led to the development of in-silico methodologies for generating computationally optimized broadly reactive antigens (COBRAs) to improve seasonal influenza vaccines.MethodsIn this study, immunologically naïve mice were intramuscularly vaccinated with mRNA encoding H1 and H3 COBRA hemagglutinins (HA) or wild-type (WT) influenza HAs encapsulated in lipid nanoparticles (LNPs).ResultsMice vaccinated with H1 and H3 COBRA HA-encoding mRNA vaccines generated robust neutralizing serum antibody responses against more antigenically distinct contemporary and future drifted H1N1 and H3N2 influenza strains than those vaccinated with WT H1 and H3 HA-encoding mRNA vaccines. The H1 and H3 COBRA HA-encoding mRNA vaccines also prevented influenza illness, including severe disease in the mouse model against H1N1 and H3N2 viruses.ConclusionsThis study highlights the potential benefits of combining universal influenza antigen design technology with modern vaccine delivery platforms and exhibits how these vaccines can be advantageous over traditional WT vaccine antigens at eliciting superior protective antibody responses against a broader number of influenza virus isolates. |
| first_indexed | 2024-04-25T00:46:15Z |
| format | Article |
| id | doaj.art-48163d9e14e049479867dce76358abc2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-25T00:46:15Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-48163d9e14e049479867dce76358abc22024-03-12T04:51:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13346701334670mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020James D. Allen0James D. Allen1James D. Allen2Ted M. Ross3Ted M. Ross4Ted M. Ross5Ted M. Ross6Center for Vaccines and Immunology, University of Georgia, Athens, GA, United StatesDepartment of Infectious Diseases, University of Georgia, Athens, GA, United StatesFlorida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, United StatesCenter for Vaccines and Immunology, University of Georgia, Athens, GA, United StatesDepartment of Infectious Diseases, University of Georgia, Athens, GA, United StatesFlorida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, United StatesDepartment of Infection Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United StatesBackgroundThe implementation of mRNA vaccines against COVID-19 has successfully validated the safety and efficacy of the platform, while at the same time revealing the potential for their applications against other infectious diseases. Traditional seasonal influenza vaccines often induce strain specific antibody responses that offer limited protection against antigenically drifted viruses, leading to reduced vaccine efficacy. Modern advances in viral surveillance and sequencing have led to the development of in-silico methodologies for generating computationally optimized broadly reactive antigens (COBRAs) to improve seasonal influenza vaccines.MethodsIn this study, immunologically naïve mice were intramuscularly vaccinated with mRNA encoding H1 and H3 COBRA hemagglutinins (HA) or wild-type (WT) influenza HAs encapsulated in lipid nanoparticles (LNPs).ResultsMice vaccinated with H1 and H3 COBRA HA-encoding mRNA vaccines generated robust neutralizing serum antibody responses against more antigenically distinct contemporary and future drifted H1N1 and H3N2 influenza strains than those vaccinated with WT H1 and H3 HA-encoding mRNA vaccines. The H1 and H3 COBRA HA-encoding mRNA vaccines also prevented influenza illness, including severe disease in the mouse model against H1N1 and H3N2 viruses.ConclusionsThis study highlights the potential benefits of combining universal influenza antigen design technology with modern vaccine delivery platforms and exhibits how these vaccines can be advantageous over traditional WT vaccine antigens at eliciting superior protective antibody responses against a broader number of influenza virus isolates.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1334670/fullinfluenzavaccinemRNAuniversalhemagglutininH1N1 |
| spellingShingle | James D. Allen James D. Allen James D. Allen Ted M. Ross Ted M. Ross Ted M. Ross Ted M. Ross mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020 Frontiers in Immunology influenza vaccine mRNA universal hemagglutinin H1N1 |
| title | mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020 |
| title_full | mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020 |
| title_fullStr | mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020 |
| title_full_unstemmed | mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020 |
| title_short | mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020 |
| title_sort | mrna vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted h1n1 and h3n2 influenza viruses isolated between 2018 2020 |
| topic | influenza vaccine mRNA universal hemagglutinin H1N1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1334670/full |
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