tetano
Editor, Senior Moderator
Int Immunol. 2018 Dec 7. doi: 10.1093/intimm/dxy069. [Epub ahead of print]
[h=1]A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection.[/h] Yamamoto T[SUP]1,[/SUP][SUP]2[/SUP], Masuta Y[SUP]1,[/SUP][SUP]3[/SUP], Momota M[SUP]1,[/SUP][SUP]4[/SUP], Kanekiyo M[SUP]5[/SUP], Kanuma T[SUP]1,[/SUP][SUP]6[/SUP], Takahama S[SUP]2,[/SUP][SUP]6[/SUP], Moriishi E[SUP]2[/SUP], Yasutomi Y[SUP]6[/SUP], Saito T[SUP]7[/SUP], Graham BS[SUP]5[/SUP], Takahashi Y[SUP]8[/SUP], Ishii KJ[SUP]1,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 β-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 FcRγ-deficient mice. Our results indicated that FcγR-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.
PMID: 30535055 DOI: 10.1093/intimm/dxy069
[h=1]A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection.[/h] Yamamoto T[SUP]1,[/SUP][SUP]2[/SUP], Masuta Y[SUP]1,[/SUP][SUP]3[/SUP], Momota M[SUP]1,[/SUP][SUP]4[/SUP], Kanekiyo M[SUP]5[/SUP], Kanuma T[SUP]1,[/SUP][SUP]6[/SUP], Takahama S[SUP]2,[/SUP][SUP]6[/SUP], Moriishi E[SUP]2[/SUP], Yasutomi Y[SUP]6[/SUP], Saito T[SUP]7[/SUP], Graham BS[SUP]5[/SUP], Takahashi Y[SUP]8[/SUP], Ishii KJ[SUP]1,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 β-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 FcRγ-deficient mice. Our results indicated that FcγR-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.
PMID: 30535055 DOI: 10.1093/intimm/dxy069