Abstract
Abstract The global outbreak of 2009 H1N1 influenza pandemic emphasized the need for an effective vaccine adjuvant. Here, we examined the adjuvant efficacy of γ-PGA/chitosan nanogel (PC nanogel) for the 2009 H1N1 pandemic influenza vaccine antigen in mice and ferrets. Compared with alum, PC nanogel dramatically enhanced the protective efficacy of this vaccine, with animals exhibiting increased pandemic HA-specific antibody production, higher neutralization activity (HI titer), and earlier virus clearance from lung tissues after homologous (pandemic H1N1) and heterosubtypic (H3N2) viral challenges. In particular, approximately 4-fold higher influenza-specific cell-medicated immunity was observed in mice vaccinated with PC nanogel compared to alum, perhaps due to the dramatic enhancement of antigen uptake by immature dendritic cells. The results from T cell-depletion experiments indicated that the heterosubtypic cross-reactivity of PC nanogel was mediated by CD8+ T cells. Additionally, the long-lasting protection (100% at 6 months) against virus challenge after immunization and a one-twelfth dose-sparing effect were observed following vaccination with PC nanogel-adjuvanted vaccine but not with alum-adjuvanted vaccine. Together, these results strongly suggest that PC nanogel may be a promising candidate adjuvant for the influenza vaccine.
Published Version
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