Improvement of the aging-related reduced efficacy of the H1N1 pandemic influenza vaccine by the complex of poly-γ-glutamic acid and alum

Abstract

Abstract Highly contagious respiratory diseases caused by viral infections, like influenza are a constantly emerging threat, particularly among the elderly. Vaccination is one of the most effective strategy for preventing influenza, but the aged-related reduced efficacy of the influenza vaccine remains an unresolved problem. Here, we demonstrate that the aging-related reduced efficacy of the influenza vaccine can be improved by the complex of poly-γ-glutamic acid (γ-PGA) and alum called PGA/Alum, a new adjuvant capable of inducing innate and adaptive immune responses in aged mice. PGA/Alum induced activation of dendritic cells isolated from spleen of aged mice, with increases of expression of co-stimulatory molecules and production of pro-inflammatory cytokines. Although aged mice were observed decrease of T and B cell population and weaken efficacy of pandemic H1N1 influenza vaccine than young mice, PGA/Alum recovered the vaccine efficacy in aged mice. Notably, the vaccine-PGA/Alum-immunized aged mice increased hemagglutination-inhibition titers, serum-neutralization titers, cytotoxic T lymphocyte activity, and generation of multifunctional CD4+ T lymphocytes. Taken together, these results suggest that PGA/Alum could be a potent vaccine adjuvant that improves the aging-related reduced efficacy of the influenza vaccine, thereby resulting in effective prevention against influenza virus infection in the elderly. This research was funded by a grant from KRIBB Research Initiative Program (KGM9942112).