Zymosan enhances the mucosal adjuvant activity of poly(I:C) in a nasal influenza vaccine.
The synthetic double-stranded RNA polyriboinocinic polyribocytidylic acid [poly(I:C)] is a potent mucosal adjuvant in mice immunized intranasally with an inactivated influenza vaccine. In an attempt, to increase the effectiveness of a nasal poly(I:C)-combined vaccine, the effect of zymosan, a cell wall extract from Saccharomyces cervisiae was investigated, on the adjuvant activity of poly(I:C) in BALB/c mice. The addition of zymosan (10 microg) as an adjuvant in mice which were immunized intranasally with a poly(I:C) (1-5 microg)-combined vaccine (1 microg) enhanced the ability of the mice to mount an effective immune response to a lethal dose of influenza virus, and resulted in a synergistic increase in secretory IgA and serum IgG antibody levels. To define the mechanism by which zymosan enhanced the adjuvant activity of poly(I:C), bone marrow-derived dendritic cells (BM-DCs) were cultured in the presence of poly(I:C) and/or zymosan. There was a synergistic increase in cytokine production (TNF-alpha, IL-6, IL-10, and IFN-beta) in BM-DCs, together with an increase in the expression of co-stimulatory molecules (CD86 and CD40) in response to co-treatment with poly(I:C) and zymosan. This synergistic effect on cytokine production was mimicked by co-treatment with poly(I:C) and a Toll-like receptor 2 (TLR2) ligand, which represented one of the components of zymosan. The results of the current study suggest that one of the mechanisms by which zymosan enhances the adjuvant activity of poly(I:C) is through increased cytokine production by DCs involving the synergistic activation of poly(I:C)-induced TLR3- and zymosan-induced TLR2-mediated signaling pathways. J. Med. Virol. 82:476-484, 2010. (c) 2010 Wiley-Liss, Inc.
Ainai
Akira
A
Influenza Virus Research Center, National Institute of Infectious Disease, Gakuen, Musashimurayama-shi, Tokyo, Japan.
Ichinohe
Takeshi
T
Tamura
Shin-Ichi
S
Kurata
Takeshi
T
Sata
Tetsutaro
T
Tashiro
Masato
M
Hasegawa
Hideki
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000008:administration & dosage*; D016019:Survival Analysis; D015854:Up-Regulation; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D015054:Zymosan / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D015054:Zymosan; D011070:Poly I-C