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Vaccine. 2016 Sep 2. pii: S0264-410X(16)30757-5. doi: 10.1016/j.vaccine.2016.08.061. [Epub ahead of print]
M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice.
Sarawar S1, Hatta Y2, Watanabe S3, Dias P1, Neumann G3, Kawaoka Y4, Bilsel P5.
Author information
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.
Copyright ? 2016. Published by Elsevier Ltd.
KEYWORDS:
CD8 T cell; Granzyme B; IFN-γ; M2-deficient; Mucosal antibody; Single replication; Sterilizing immunity; Universal influenza vaccine
PMID: 27595896 DOI: 10.1016/j.vaccine.2016.08.061
[PubMed - as supplied by publisher]
M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice.
Sarawar S1, Hatta Y2, Watanabe S3, Dias P1, Neumann G3, Kawaoka Y4, Bilsel P5.
Author information
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.
Copyright ? 2016. Published by Elsevier Ltd.
KEYWORDS:
CD8 T cell; Granzyme B; IFN-γ; M2-deficient; Mucosal antibody; Single replication; Sterilizing immunity; Universal influenza vaccine
PMID: 27595896 DOI: 10.1016/j.vaccine.2016.08.061
[PubMed - as supplied by publisher]