Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection

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• 作者：Seol Hee Hong^a ; ^b ; ¹ ; Young-Ho Byun^c ; ¹ ; Chung Truong Nguyen^a ; Soo Young Kim^a ; Baik Lin Seong^c ; Songyong Park^d ; Gyu-Jin Woo^d ; Yeup Yoon^d ; Jeong Tae Koh^b ; Kohtaro Fujihashi^e ; Joon Haeng Rhee^a ; ^{jhrhee@chonnam.ac.kr} ; Shee Eun Lee^a ; ^b ; ^{selee@chonnam.ac.kr}
• 关键词：Flagellin ; Inactivated influenza vaccine ; Adjuvant ; Intranasal ; IgA ; Protective immunity
• 刊名：Vaccine
• 出版年：2012
• 出版时间：5 January 2012
• 年：2012
• 卷：30
• 期：2
• 页码：466-474
• 全文大小：951 K

文摘

The influenza virus, a mucosal pathogen that infects the respiratory tract, is a major global health issue. There have been attempts to mucosally administer inactivated influenza vaccines to induce both mucosal and systemic immune responses. However, mucosally administered inactivated influenza vaccine has low immunogenicity, which is partially due to the lack of an effective mucosal adjuvant. The development of a safe and effective mucosal adjuvant is a prerequisite to the practical use of a mucosal inactivated influenza vaccine. We have previously demonstrated that a bacterial flagellin, Vibrio vulnificus FlaB, when mixed with antigen and administered intranasally, exerts a strong mucosal adjuvant activity by stimulating the Toll-like receptor 5 (TLR5). In this study, we tested whether the FlaB protein could serve as an effective mucosal adjuvant for an inactivated trivalent influenza vaccine (TIV) manufactured for humans; in a murine vaccination model, this vaccine consists of A/Brisbane/59/07 (H1N1 subtype), A/Uruguay/716/07 (H3N2 subtype), and B/Florida/4/06 (B type). Intranasal co-administration of the TIV with FlaB induced prominent humoral responses as demonstrated by high influenza-specific IgA levels in both the mucosal secretions and serum and significant specific IgG induction in the systemic compartment. The FlaB protein significantly potentiated influenza-specific cytokine production by draining lymph node cells and splenocytes. The FlaB mucosal adjuvant conferred excellent protection against a lethal challenge with a live virulent virus with high hemagglutination inhibition (HAI) antibody (Ab) titers. The FlaB did not accumulate in the olfactory nerve and epithelium, guaranteeing against a retrograde uptake into the central nervous system. These results suggest that FlaB can be used as a promising mucosal adjuvant for nasal inactivated influenza vaccine development.