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M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice.
Vaccine. 2016 09 30; 34(42):5090-5098.V

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.

Authors+Show Affiliations

The Biomedical Research Institute of Southern California, Oceanside, CA 92056, USA.FluGen Inc., Madison, WI 53711, USA.Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53711, USA.The Biomedical Research Institute of Southern California, Oceanside, CA 92056, USA.Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53711, USA.Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53711, USA; Division of Virology, Department of Microbiology and Immunology, Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.FluGen Inc., Madison, WI 53711, USA. Electronic address: pbilsel@flugen.com.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27595896

Citation

Sarawar, Sally, et al. "M2SR, a Novel Live Single Replication Influenza Virus Vaccine, Provides Effective Heterosubtypic Protection in Mice." Vaccine, vol. 34, no. 42, 2016, pp. 5090-5098.
Sarawar S, Hatta Y, Watanabe S, et al. M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice. Vaccine. 2016;34(42):5090-5098.
Sarawar, S., Hatta, Y., Watanabe, S., Dias, P., Neumann, G., Kawaoka, Y., & Bilsel, P. (2016). M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice. Vaccine, 34(42), 5090-5098. https://doi.org/10.1016/j.vaccine.2016.08.061
Sarawar S, et al. M2SR, a Novel Live Single Replication Influenza Virus Vaccine, Provides Effective Heterosubtypic Protection in Mice. Vaccine. 2016 09 30;34(42):5090-5098. PubMed PMID: 27595896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice. AU - Sarawar,Sally, AU - Hatta,Yasuko, AU - Watanabe,Shinji, AU - Dias,Peter, AU - Neumann,Gabriele, AU - Kawaoka,Yoshihiro, AU - Bilsel,Pamuk, Y1 - 2016/09/03/ PY - 2016/05/17/received PY - 2016/08/08/revised PY - 2016/08/23/accepted PY - 2016/9/7/entrez PY - 2016/9/7/pubmed PY - 2017/12/8/medline KW - CD8 T cell KW - Granzyme B KW - IFN-γ KW - M2-deficient KW - Mucosal antibody KW - Single replication KW - Sterilizing immunity KW - Universal influenza vaccine SP - 5090 EP - 5098 JF - Vaccine JO - Vaccine VL - 34 IS - 42 N2 - 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. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/27595896/M2SR_a_novel_live_single_replication_influenza_virus_vaccine_provides_effective_heterosubtypic_protection_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(16)30757-5 DB - PRIME DP - Unbound Medicine ER -