Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Vaccine. 2010 Feb 3;28(5):1412-21. doi: 10.1016/j.vaccine.2009.10.148. Epub 2009 Nov 17.
Systemic immunization of cattle with H7 flagellin results in induction of both H7-specific IgA and IgG antibodies but only partially protects against subsequent colonization with Escherichia coli O157:H7. Recent studies indicate that anti-flagellin antibodies directed against TLR5 binding domains located in the conserved N- and C-terminal domains of flagellin can neutralise TLR5 activation and impair vaccine efficacy. In the current study we determined whether systemic immunization of cattle with H7 flagellin induces antibodies capable of interfering with flagellin-mediated TLR5 activation. Both anti-H7 IgG1 and IgG2 but not IgA antibodies recognised epitopes within the conserved N- and C-terminal domains of H7 flagellin, and purified H7-specific IgG but not IgA was capable of inhibiting H7-mediated TLR5 activation in vitro. These results suggest that (i) IgA and IgG isotypes originated from different populations of B cells and (ii) systemically induced H7-specific IgG but not IgA may impair innate immune responses to E. coli O157:H7 via neutralisation of TLR5 activation and subsequently reduce vaccine efficacy.
用 H7 鞭毛蛋白对牛进行全身免疫可诱导产生 H7 特异性 IgA 和 IgG 抗体，但仅能部分预防随后大肠杆菌 O157:H7 的定植。最近的研究表明，针对位于鞭毛保守的 N 端和 C 端结构域中 TLR5 结合域的抗鞭毛蛋白抗体可中和 TLR5 激活并损害疫苗效力。在本研究中，我们确定了用 H7 鞭毛蛋白对牛进行全身免疫是否会诱导产生能够干扰鞭毛蛋白介导的 TLR5 激活的抗体。抗 H7 IgG1 和 IgG2 但不是 IgA 抗体识别 H7 鞭毛蛋白保守的 N 端和 C 端结构域内的表位，并且纯化的 H7 特异性 IgG 但不是 IgA 能够在体外抑制 H7 介导的 TLR5 激活。这些结果表明，（i）IgA 和 IgG 同种型源自不同的 B 细胞群体，（ii）系统诱导的 H7 特异性 IgG 但不是 IgA 可能通过中和 TLR5 激活来抑制对大肠杆菌 O157:H7 的先天免疫反应，从而降低疫苗效力。
