TY - JOUR
T1 - Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines
AU - Hayashi, Masayuki
AU - Aoshi, Taiki
AU - Haseda, Yasunari
AU - Kobiyama, Kouji
AU - Wijaya, Edward
AU - Nakatsu, Noriyuki
AU - Igarashi, Yoshinobu
AU - Standley, Daron M.
AU - Yamada, Hiroshi
AU - Honda-Okubo, Yoshikazu
AU - Hara, Hiromitsu
AU - Saito, Takashi
AU - Takai, Toshiyuki
AU - Coban, Cevayir
AU - Petrovsky, Nikolai
AU - Ishii, Ken J.
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.
AB - Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.
KW - Adjuvant
KW - Inulin
KW - Macrophage
KW - Particle
KW - Vaccine
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U2 - 10.1016/j.ebiom.2016.11.015
DO - 10.1016/j.ebiom.2016.11.015
M3 - Article
C2 - 27919753
AN - SCOPUS:85007415529
VL - 15
SP - 127
EP - 136
JO - EBioMedicine
JF - EBioMedicine
SN - 2352-3964
ER -