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BackgroundInfluenza vaccines are prepared annually based on global epidemiological surveillance data. However, since there is no method by which to predict the influenza strain that will cause the next pandemic, the demand to develop new vaccination strategies with broad cross-reactivity against influenza viruses are clearly important. The ectodomain of the influenza M2 protein (M2e) is an attractive target for developing a vaccine with broad cross-reactivity. For these reasons, we investigated the efficacy of an inactivated H9N2 virus vaccine (a-H9N2) mixed with M2e (1xM2e or 4xM2e) proteins expressed in Escherichia coli, which contains the consensus of sequence the extracellular domain of matrix 2 (M2e) of A/chicken/Vietnam/27262/09 (H5N1) avian influenza virus, and investigated its humoral immune response and cross-protection against influenza A viruses.ResultsMice were intramuscularly immunized with a-H9N2, 1xM2e alone, 4xM2e alone, a-H9N2/1xM2e, or a-H9N2/4xM2e. Three weeks post-vaccination, mice were challenged with lethal homologous (A/ chicken /Korea/ma163/04, H9N2) or heterosubtypic virus (A/Philippines/2/82, H3N2 and A/aquatic bird/Korea/maW81/05, H5N2). Our studies demonstrate that the survival of mice immunized with a-H9N2/1xM2e or with a-H9N2/4xM2e (100% survival) was significantly higher than that of mouse-adapted H9N2 virus-infected mice vaccinated with 1xM2e alone or with 4xM2e alone (0% survival). We also evaluated the protective efficacy of the M2e + vaccine against infection with mouse-adapted H5N2 influenza virus. Protection from death in the control group (0% survival) was similar to that of the 1×M2e alone and 4xM2e alone-vaccinated groups (0% survival). Only 40% of mice vaccinated with vaccine alone survived challenge with H5N2, while the a-H9N2/1×M2e and a-H9N2/4×M2e groups showed 80% and 100% survival following mouse-adapted H5N2 challenge, respectively. We also examined cross-protection against human H3N2 virus and found that the a-H9N2/1×M2e group displayed partial cross-protection against H3N2 (40% survival), whereas vaccine alone, 1×M2e alone, 4×M2e alone, or H9N2/1×M2e groups showed incomplete protection (0% survival) in response to challenge with a lethal dose of human H3N2 virus.ConclusionsTaken together, these results suggest that prokaryote-expressed M2e protein improved inactivated H9N2 virus vaccine efficacy and achieved cross-protection against lethal influenza A virus infection in mice.

We found a relatively high frequency of unique amantadine-resistant H3N2 and H9N2 avian influenza viruses (Val27Ile on M2 protein) isolated from live poultry markets in South Korea and confirmed that a Val27Ile single substitution in the M2 protein is enough to acquire the amantadine resistance phenotype by using reverse-genetically created human-avian reassortant viruses.

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Background Salivary gland neoplasms are relatively rare and comprise only 1%‐4% of all human neoplasms. Salivary gland neoplasms also show an extremely wide range of morphological diversity. Currently, the genetic alterations and corresponding molecular mechanisms underlying salivary gland neoplasms development remain largely unknown. Method We generated an inducible Tet‐MAP3K8::MMTV‐rTA mouse model by crossing the MAP3K8 transgenic mice with MMTR‐rTA transgenic mice to express MAP3K8 in the salivary gland. Results MAP3K8 overexpression in the murine salivary glands of Tet‐MAP3K8::MMTR‐rTA transgenic mice induces tumorigenesis. Pathological investigations reveal partial fibrosis and adenosis of salivary glands, and foci of atypical squamoid cellular proliferation, which represent invasive squamous cell carcinoma (SCC). Conclusion MAP3K8 overexpression is associated with SCC development in murine salivary glands. It provides an in vivo framework for the understanding of molecular mechanisms underlying SCC development in the salivary glands and also for the development of a future therapeutic strategy targeting this tumor type.