Protective Immune Responses were Elicited by Intranasal Inactivated Influenza Vaccines Combined with a Mucosal Adjuvant Candidate, Unevenly Structured Poly(I:C) Koshiro Tabata1,2, Yuki Ohara1, Akira Ainai1, Yohsuke Harada2, Tetsuo Nakano3, Tadaki Suzuki1, Hideki Hasegawa1 1Department of Pathology, National Institute of Infectious Diseases; 2Graduate School of Pharmaceutical Sciences, Tokyo University of Science; 3R&BD Department, Kyowa Hakko Bio Co., Ltd.
Intranasal inactivated influenza vaccine can induce sufficient antibody responses on respiratory mucosa for protecting from influenza virus infection, and then is expected to be more effective for preventing influenza than injectable vaccines. Currently, the intranasal inactivated influenza vaccine using inactivated whole influenza virions is one of the most promising candidates for intranasal inactivated influenza vaccine. However, the intranasal inactivated vaccines often demand multiple shots and higher antigen dose than those in conventional injectable vaccines for inducing a sufficient immune response, which stimulates interests in developing mucosal adjuvants. Previously, we reported that synthetic double stranded RNA (dsRNA), poly(I:C) can enhance immune responses induced by intranasal inactivated influenza vaccine for protecting against virus infection. However, it has been also reported that poly(I:C) induces a number of adverse events in humans, including inflammation, erythema and fever. Therefore, poly(I:C) has to be modified to improve safety profile to clinical use as a mucosal adjuvant. In this study, we evaluated the unevenly structured poly(I:C) compound with low toxicity, uPIC100, as a mucosal adjuvant candidate for intranasal inactivated influenza vaccine in various combinations of vaccine antigens including split HA antigens and recombinant HA proteins using mouse and nonhuman primate models. We demonstrated that intranasal administration of uPIC100 combined with various vaccine antigens induced protective immunity against influenza virus infection in mouse and nonhuman primate model and elicited systemic and mucosal antibodies production. These observations indicate that uPIC100 is a promising mucosal adjuvant candidate for intranasal inactivated influenza vaccines.
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