1. A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection.
- Author
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Yamamoto T, Masuta Y, Momota M, Kanekiyo M, Kanuma T, Takahama S, Moriishi E, Yasutomi Y, Saito T, Graham BS, Takahashi Y, and Ishii KJ
- Subjects
- Animals, Female, Humans, Influenza Vaccines chemistry, Mice, Mice, Inbred C57BL, Toll-Like Receptor 9 agonists, Toll-Like Receptor 9 immunology, Hemagglutinins, Viral immunology, Influenza Vaccines immunology, Influenza, Human immunology, Nanoparticles chemistry, Orthomyxoviridae Infections immunology, Receptors, Fc immunology
- Abstract
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., (© The Japanese Society for Immunology. 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
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