M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice. Issue 42 (30th September 2016)

• Record Type: Journal Article
• Authors: Sarawar, Sally; Hatta, Yasuko; Watanabe, Shinji; Dias, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro; Bilsel, Pamuk
• Is Part Of: Vaccine. Volume 34:Issue 42(2016)
• Page Start: 5090
• Page End: 5098
• Publication Date: 2016-09-30
• Subjects: ADCC antibody-dependent cellular cytotoxicity -- Aichi influenza A/Aichi/2/1968 -- APC allophycocyanin -- BAL bronchoalveolar lavage -- BSA bovine serum albumin -- CPE cytopathic effect -- FCS fetal calf serum -- FITC fluorescein isothiocyanate -- HAI hemagglutination inhibition -- IFN interferon -- IN intranasal -- IM intramuscular -- IP intraperitoneal -- LAIV live attenuated influenza vaccine -- LDS lithium dodecyl sulfate -- LOD limit of detection -- M2SR M2-deficient single replication vaccine virus -- M2CK Madin-Darby canine kidney cells expressing M2 protein -- MDCK Madin-Darby canine kidney -- MEM minimal essential medium -- MLD50 50% mouse lethal dose -- MOI multiplicity of infection -- OD optical density -- ORF open reading frame -- PE phycoerythrin -- PerCP peridinin chlorophyll protein complex -- PFU plaque-forming unit -- PR8 influenza A/Puerto Rico/8/34 -- RDE receptor destroying enzyme -- RSV respiratory syncytial virus -- TCID50 50% tissue culture infectious dose -- TMB tetramethylbenzidine -- TPCK L-(tosylamido-2-phenyl) ethyl chloromethyl ketone; Universal influenza vaccine -- M2-deficient -- Single replication -- Sterilizing immunity -- Mucosal antibody -- CD8 T cell -- Granzyme B -- IFN-γ; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.08.061
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: M2SR is anM2 -deletedS ingleR eplication novel influenza vaccine. M2SR provides homosubtypic and heterosubtypic protection in mice. M2SR elicits cross-reactive T cell responses recalled upon heterosubtypic challenge. 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.