Schulze Kai, Medina Eva, Chhatwal Gursharan S, Guzmán Carlos A
Department of Microbial Pathogenesis and Vaccine Research, Division of Microbiology, GBF-German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Vaccine. 2003 May 16;21(17-18):1958-64. doi: 10.1016/s0264-410x(02)00803-4.
Protective immunity against Streptococcus pyogenes can be induced by intranasal vaccination with the fibronectin-binding domain (H12 fragment) of the fibronectin-binding protein I (SfbI) co-administered with the B subunit of the cholera toxin (CTB) as mucosal adjuvant. However, intranasal administration of A-B moiety bacterial toxins or their derivatives has been associated with potentially severe side effects. Since the SfbI protein exhibits adjuvant properties, we investigated whether vaccination with the H12 fragment alone is sufficient to promote long-lasting protection. The obtained results demonstrated that the humoral and cellular immune responses stimulated at both systemic and mucosal levels were almost identical when mice were vaccinated with the H12 fragment in the presence or absence of CTB. Immunized mice were protected against challenge with a lethal dose of S. pyogenes given 36 or 110 days after primary vaccination to the same extent (80% survival), regardless of CTB incorporation. These results demonstrate that vaccination with the H12 fragment stimulates long-lasting protective immunity. The adjuvant properties exhibited by the fibronectin-binding domain of the SfbI protein strength the potential of this antigen for inclusion in multi-component vaccines against S. pyogenes.
用纤连蛋白结合蛋白I(SfbI)的纤连蛋白结合结构域(H12片段)与霍乱毒素B亚基(CTB)作为粘膜佐剂共同经鼻内接种,可诱导针对化脓性链球菌的保护性免疫。然而,经鼻内给予A-B部分细菌毒素或其衍生物已被证实与潜在的严重副作用有关。由于SfbI蛋白具有佐剂特性,我们研究了单独用H12片段进行疫苗接种是否足以促进长期保护。所得结果表明,无论有无CTB,当用H12片段给小鼠接种疫苗时,在全身和粘膜水平刺激产生的体液免疫和细胞免疫反应几乎相同。初次接种疫苗36天或110天后,用致死剂量的化脓性链球菌攻击免疫小鼠,无论是否加入CTB,小鼠的存活率均相同(80%存活),均受到了保护。这些结果表明,用H12片段接种疫苗可刺激产生持久的保护性免疫。SfbI蛋白的纤连蛋白结合结构域所表现出的佐剂特性增强了该抗原用于化脓性链球菌多组分疫苗的潜力。