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Introduction: Current influenza vaccines can prevent disease caused by influenza viruses but require annual administration and almost yearly reformulation. An attractive alternative approach would be to use a vaccine that provides broad and, ideally, lifelong protection against all influenza A and B virus strains. The extracellular domain of matrix protein 2 (M2e) of influenza A viruses is conserved and thus fits well in such a broadly protective vaccine. Areas covered: Recent advances in M2e vaccine design, the mode of action of M2e-based immunity and clinical progress of M2-based influenza vaccines. Expertcommentary: Many M2e vaccine have been successfully tested for efficacy against a panel of divergent influenza viruses in animal models. More recently, clinical studies have been conducted with M2e vaccine candidates, which demonstrated their safety and immunogenicity in humans. Efficacy studies in humans are still needed to provide evidence that an M2e-based vaccine can protect against human influenza. [ABSTRACT FROM PUBLISHER]

Optineurin (OPTN) is an evolutionary conserved and ubiquitously expressed ubiquitinbinding protein that has been implicated in glaucoma, Paget bone disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases. From in vitro studies, OPTN was shown to suppress TNF-induced NF-κB signaling and virus-induced IRF signaling, and was identified as an autophagy receptor required for the clearance of cytosolic Salmonella upon infection. To assess the in vivo functions of OPTN in inflammation and infection, we generated OPTN-deficient mice. OPTN knockout mice are born with normal Mendelian distribution and develop normally without any signs of spontaneous organ abnormality or inflammation. However, no differences in NF-κB activation could be observed in OPTN knockoutmice or fibroblasts derived from thesemice upon TNF or LPS treatment. Primary bone marrow-derived macrophages from OPTN-deficient mice had slightly impaired IRF signaling and reduced IFN type I production in response to LPS or poly(I,C). Finally, OPTNdeficient mice were more susceptible to infection with Salmonella, confirming in vivo the importance of OPTN in bacterial clearance. [ABSTRACT FROM AUTHOR]

Pregnant women and neonates represent high-risk groups for influenza infection, and in general have suppressed responses to standard influenza vaccines due to pregnancy-associated immune suppression and immune system immaturity, respectively. We therefore wished to test whether addition of Advax™, a polysaccharide adjuvant based on delta inulin, to an inactivated influenza vaccine (A/H1N1/PR8) administered during pregnancy would safely enhance vaccine immunogenicity and thereby provide improved protection of pregnant mothers and their newborns. Pregnant mice received a single intramuscular injection of β-propiolactone-inactivated H1N1 antigen alone or with Advax adjuvant. Pregnant dams receiving Advax-adjuvanted vaccine exhibited significantly increased serum and breast milk anti-influenza IgG titers. This translated into higher serum anti-influenza IgG titers in the pups of these dams. Complete protection was seen in pups of dams that received Advax-adjuvanted vaccine whereas no survival was seen in pups of control mothers or mothers immunized with unadjuvanted influenza vaccine. Cross-fostering studies confirmed that enhanced protection of pups of dams that received Advax-adjuvanted vaccine was mediated by enhanced transfer of maternal IgG to the pups via breast-feeding. The delta inulin adjuvant was not associated with any reproductive or developmental adverse effects. This study shows that Advax adjuvant was safe when administered with influenza vaccine during pregnancy and provided protection of pups via enhanced breast milk transfer of anti-influenza antibodies, not seen with administration of unadjuvanted vaccine. [ABSTRACT FROM AUTHOR]

Background: Human Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease (HFMD) in young children. It is often associated with severe neurological diseases and has caused high mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no effective vaccine and antiviral agents available against EV71 infections. VP1 is one of the major immunogenic capsid protein of EV71 and plays a crucial role in viral infection. Antibodies against VP1 are important for virus neutralization. Methodology/Principal Finding: In the present study, infectious EV71 viruses were generated from their synthetic complementary DNA using the human RNA polymerase I reverse genetics system. Secondly, the major immunogenic capsid protein (VP1) of EV71-Fuyang (subgenogroup C4) was displayed on the surface of recombinant baculovirus Bac-Pie1-gp64- VP1 as gp64 fusion protein under a novel White Spot Syndrome Virus (WSSV) immediate early ie1 promoter. Baculovirus expressed VP1 was able to maintain its structural and antigenic conformity as indicated by immunofluorescence assay and western blot analysis. Interestingly, our results with confocal microscopy revealed that VP1 was able to localize on the plasma membrane of insect cells infected with recombinant baculovirus. In addition, we demonstrated with transmission electron microscopy that baculovirus successfully acquired VP1 from the insect cell membrane via the budding process. After two immunizations in mice, Bac-Pie1-gp64-VP1 elicited neutralization antibody titer of 1:64 against EV71 (subgenogroup C4) in an in vitro neutralization assay. Furthermore, the antisera showed high cross-neutralization activities against all 11 subgenogroup EV71 strains. Conclusion: Our results illustrated that Bac-Pie1-gp64-VP1 retained native epitopes of VP1 and acted as an effective EV71 vaccine candidate which would enable rapid production without any biosafety concerns. [ABSTRACT FROM AUTHOR]