Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
Vaccine. 2011 Jul 26;29(33):5368-78. doi: 10.1016/j.vaccine.2011.05.090. Epub 2011 Jun 12.
We have reported that Surfacten(®) (St), a bovine pulmonary surfactant free of antigenic c-type lectins, is a useful mucosal adjuvant for nasal vaccination. To prepare ample supplies a synthetic adjuvant that mimics St, we analyzed essential constituents of St for mucosal adjuvanticity. Intranasal inoculation of influenza virus hemagglutinin (HA) vaccine combined with St free of surfactant protein (SP)-C resulted in failure of HA vaccine delivery to dendritic cells and loss of local and systemic immune responses. Naïve bovine SP-C, synthetic human or bovine SP-C peptide reconstituted with three major St lipids restored delivery activity and local and systemic immune responses to levels similar to those of St and provided almost complete protection against lethal doses of influenza virus challenge in mice. The delivery of fluoresceinated HA vaccine to cultured dendritic cells was significantly enhanced by co-administration of St or synthetic adjuvant, and moderately stimulated the expression of MHC class II and CD86. In addition, both St and synthetic adjuvant markedly sustained HA vaccine and achieved a wide antigen distribution in murine nasal cavity. These results suggest that synthetic mucosal adjuvant reconstituted with SP-C peptide and major St lipids is useful for ample supply of the potent mucosal adjuvant as an antigen delivery vehicle for intranasal vaccination.
我们曾报道过,Surfacten(®)(St)是一种不含抗原 C 型凝集素的牛肺表面活性剂,是一种用于鼻内接种的有用黏膜佐剂。为了制备充足的供应品,我们分析了 St 的黏膜佐剂的基本成分,以模拟 St。流感病毒血凝素 (HA) 疫苗与不含表面活性剂蛋白 (SP)-C 的 St 联合鼻内接种导致 HA 疫苗无法递送至树突状细胞,丧失局部和全身免疫应答。天然牛 SP-C、合成的人或牛 SP-C 肽与三种主要的 St 脂质重新构成,恢复了递呈活性以及局部和全身免疫应答,其水平与 St 相似,并为小鼠提供了对致死剂量流感病毒攻击的几乎完全保护。荧光标记的 HA 疫苗与 St 或合成佐剂共同给药,可显著增强对培养的树突状细胞的递呈,适度刺激 MHC Ⅱ类和 CD86 的表达。此外,St 和合成佐剂都可显著维持 HA 疫苗,并在小鼠鼻腔内实现广泛的抗原分布。这些结果表明,用 SP-C 肽和主要的 St 脂质重新构成的合成黏膜佐剂可用于大量供应有效的黏膜佐剂,作为鼻内接种的抗原传递载体。