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Updated: Mar 15, 2026
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice
Sally Sarawar1, Yasuko Hatta2, Shinji Watanabe3
1The Biomedical Research Institute of Southern California, Oceanside, CA 92056, USA.
Abstract:
Despite the annual public health burden of seasonal influenza and the continuing threat of a global pandemic posed by the emergence of highly pathogenic/pandemic strains, conventional influenza vaccines do not provide universal protection, and exhibit suboptimal efficacy rates, even when they are well matched to circulating strains. To address the need for a highly effective universal influenza vaccine, we have developed a novel M2-deficient single replication vaccine virus (M2SR) that induces strong cross-protective immunity against multiple influenza strains in mice. M2SR is able to infect cells and expresses all viral proteins except M2, but is unable to generate progeny virus. M2SR generated from influenza A/Puerto Rico/8/34 (H1N1) protected mice against lethal challenge with influenza A/Puerto Rico/8/34 (H1N1, homosubtypic) and influenza A/Aichi/2/1968 (H3N2, heterosubtypic). The vaccine induced strong systemic and mucosal antibody responses of both IgA and IgG classes. Strong virus-specific T cell responses were also induced. Following heterologous challenge, significant numbers of IFN-γ-producing CD8 T cells, with effector or effector/memory phenotypes and specific for conserved viral epitopes, were observed in the lungs of vaccinated mice. A substantial proportion of the CD8 T cells expressed Granzyme B, suggesting that they were capable of killing virus-infected cells. Thus, our data suggest that M2-deficient influenza viruses represent a promising new approach for developing a universal influenza vaccine.
Insights
A novel M2-deficient single replication vaccine virus (M2SR) shows promise for a universal influenza vaccine. This M2SR induced cross-protective immunity against multiple influenza strains in mice, offering a potential solution for seasonal flu and pandemic threats.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Seasonal influenza poses an annual public health burden.
- The threat of global pandemics from novel influenza strains persists.
- Current influenza vaccines have limitations in universal protection and efficacy.
Purpose of the Study:
- To develop a highly effective universal influenza vaccine.
- To investigate the potential of M2-deficient single replication vaccine virus (M2SR) for inducing cross-protective immunity.
Main Methods:
- Development of a novel M2-deficient single replication vaccine virus (M2SR).
- Vaccination of mice with M2SR derived from influenza A/Puerto Rico/8/34 (H1N1).
- Challenge studies with homosubtypic (H1N1) and heterosubtypic (H3N2) influenza strains.
- Assessment of systemic and mucosal antibody responses (IgA, IgG).
- Analysis of virus-specific T cell responses, including CD8 T cells in the lungs.
Main Results:
- M2SR protected mice against lethal challenge with both homosubtypic and heterosubtypic influenza strains.
- Strong systemic and mucosal antibody responses (IgA and IgG) were induced.
- Robust virus-specific T cell responses were observed, including IFN-γ-producing CD8 T cells with effector phenotypes.
- CD8 T cells expressing Granzyme B indicated cytotoxic potential against infected cells.
Conclusions:
- M2-deficient single replication viruses (M2SR) are a promising approach for universal influenza vaccine development.
- M2SR elicits broad cross-protective immunity through both antibody and T cell responses.
- This novel vaccine strategy warrants further investigation for combating influenza threats.
