| First Author | Yamamoto T | Year | 2019 |
| Journal | Int Immunol | Volume | 31 |
| Issue | 2 | Pages | 81-90 |
| PubMed ID | 30535055 | Mgi Jnum | J:271308 |
| Mgi Id | MGI:6279138 | Doi | 10.1093/intimm/dxy069 |
| Citation | Yamamoto T, et al. (2019) A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcgammaR-mediated protection against heterologous lethal influenza virus infection. Int Immunol 31(2):81-90 |
| abstractText | The development of a universal influenza vaccine that can provide a robust and long-lasting protection against a broader range of influenza virus strains is a global public health priority. One approach to improve vaccine efficacy is to use an adjuvant to boost immune responses to the target antigens; nevertheless, the role of adjuvants in the context of influenza vaccines is not fully understood. We have previously developed the K3-schizophyllan (SPG) adjuvant, which is composed of nanoparticulated oligodeoxynucleotides K3, a TLR9 agonist, with SPG, a non-agonistic beta-glucan ligand of Dectin-1. In this study, K3-SPG given with conventional influenza hemagglutinin (HA) split vaccine (K3-SPG HA) conferred protection against antigenically mismatched heterologous virus challenge. While K3-SPG HA elicited robust cross-reactive HA-specific IgG2c and CD8 T-cell responses, CD8 T-cell depletion had no impact on this cross-protection. In contrast, K3-SPG HA was not able to confer protection against heterologous virus challenge in FcRgamma-deficient mice. Our results indicated that FcgammaR-mediated antibody responses induced by the HA antigen and K3-SPG adjuvant were important for potent protection against antigenically mismatched influenza virus infection. Thus, we demonstrated that the K3-SPG-adjuvanted vaccine strategy broadens protective immunity against influenza and provides a basis for the development of next-generation influenza vaccines. |
