Influenza virus vaccine (Il-Yang Pharmaceutical)

Vaccine adverse events and controversial safety issues have occurred in recent decades in Japan: aseptic meningitis following the measles-mumps-rubella combined vaccine (MMR), anaphylaxis after immunization with live virus vaccines and inactivated split influenza vaccine, an increased incidence of febrile illness following the simultaneous administration of inactivated vaccines, and chronic pain with neurological illness after immunization with the human papilloma virus vaccine (HPV). Vaccine adverse events are a matter of concern for the public as well as general practitioners; some are within the range of assumptions that adverse reactions after live attenuated vaccines are related to the nature of their parental wild-type viruses. Vaccines stimulate the innate immunity of host immunological defense mechanisms and induce the development of specific acquired immunity. Some adverse events related to autoimmune responses have been reported, such as idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis (ADEM). Although a plausible relationship was not demonstrated, the possibility of an association cannot be denied. The pathogenicity of adverse reactions was investigated for anaphylactic reactions, systemic and local reactions following vaccinations. Initial innate immune responses are essential for the development of acquired immunity and are related to adverse events from different viewpoints.

Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating in vitro dendritic cells (DCs), in vivo innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs in vitro to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination.