A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging |
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Authors: | Asanuma Hideki Zamri Normaiza Binti Sekine Shinichi Fukuyama Yoshiko Tokuhara Daisuke Gilbert Rebekah S Fukuiwa Tatsuya Fujihashi Keiko Sata Tetsutaro Tashiro Masato Fujihashi Kohtaro |
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Affiliation: | a Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan b Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA c Department of Applied Biochemistry, School or Engineering, Tokai University, Hiratsuka-shi, Kanagawa, Japan d Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan e Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan |
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Abstract: | Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)3 as a dendritic cell (DC)-targeting double mucosal adjuvant elicited ovalbumin-specific secretory IgA (S-IgA) antibody (Ab) responses, we examined whether this double adjuvant could induce influenza-specific protective immunity in aged mice. A double adjuvant plus A/Puerto Rico/8/34 (PR8) hemagglutinin (HA) induced increased numbers of CD11b+ CD11c+ DCs and both CD4+ Th1- and Th2-type responses in the nasopharyngeal-associated lymphoreticular tissue, nasal passages and cervical lymph nodes. Further, increased levels of PR8 HA-specific S-IgA Ab responses were detected in the upper respiratory tact (URT) of aged and young adult mice given nasal PR8 HA with this double adjuvant. Thus, when mice were challenged with PR8 virus via the nasal route, both aged and young adult mice given nasal vaccine exhibited complete protection. Further, IgA-deficient mice nasally immunized with a double adjuvant influenza vaccine failed to provide protection against PR8 challenge. These results indicate that a nasal double adjuvant successfully induces PR8 HA-specific IgA Ab responses in both young adult and aged mice, which are essential for the prevention of influenza infection in the murine URT. |
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Keywords: | Influenza Mucosal vaccine DC Aged mice |
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