The complex of poly-γ-glutamic acid and aluminum salts ameliorates the reduced efficacy of the influenza H1N1 vaccine in aged mice

Abstract

Abstract Influenza is a highly contagious respiratory disease caused by the influenza A viruses and results in public health threat like seasonal epidemics and sporadic pandemics. Although vaccination is considered to be one of the most effective strategy for preventing the disease, the low efficacy of the influenza vaccine has been reported in the elderly. Here, we examined that the aging-related reduced efficacy of the influenza vaccine can be ameliorated by the complex of poly-γ-glutamic acid (γ-PGA) and alum (PGA/Alum), a novel adjuvant capable of inducing both humoral and cellular immune responses, using an aged mouse model. PGA/Alum induced activation of dendritic cells from aged mice, accompanied with increase of both expression of co-stimulatory molecules and production of pro-inflammatory cytokines. In addition, PGA/Alum enhanced the protective efficacy of pandemic influenza H1N1 (pH1N1) vaccine in aged mice, with earlier virus clearance after A/California/4/2009 (pH1N1) viral challenge, increased hemagglutination-inhibition titers, activity of cytotoxic T lymphocytes, and generation of multifunctional T lymphocytes. Taken together, these results suggest that PGA/Alum is a potent vaccine adjuvant that could improve the reduced vaccine efficacy of aging, thereby leading to prevention of influenza virus infection in the immune compromised populations.