Zhong W, Gern L, Kramer M, Wallich R, Simon M M
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Eur J Immunol. 1997 Nov;27(11):2942-7. doi: 10.1002/eji.1830271129.
Antibodies to the outer surface lipoprotein A (OspA) of Borrelia burgdorferi confer protection to SCID mice against subsequent tick-borne or experimental infection. However, OspA-specific antibodies are hardly detectable in naturally infected humans, dogs, hamsters and mice. This is most probably due to limited expression of OspA on spirochetes transmitted from the vector to the host. Here we have tested whether T cell priming of mice would lead to the induction of protective OspA-specific antibodies upon infection. It is shown that AKR/N mice, previously immunized with either a single T helper cell peptide of OspA, or a mixture of 27 peptides spanning the entire molecule, develop OspA-specific IgM or IgG antibodies, including those to a prominent protective B cell epitope of OspA. LA-2, within 7 days of infection with low doses (10(3)) of culture-derived spirochetes. In marked contrast, the same groups of pre-sensitized mice failed to generate any detectable OspA-specific antibodies after tick-borne infection for more than 40 days after infection. All mice, irrespective of their state of T cell immunity to OspA or the mode of infection, produced similar levels of OspC-specific IgM and IgG antibodies as early as day 14 after infection. None of the mice previously immunized with OspA peptides were protected against experimental infection, in spite of the appearance of protective antibodies. It is clear from these data that, in contrast to culture-derived spirochetes, the naturally transmitted pathogen fails to express OspA within the mammalian host at levels sufficient for induction of B cell responses, even in the presence of pre-activated T helper cells. Together with the fact that OspA-specific antibodies are mainly operative by eliminating spirochetes from the vector during infestation, the data suggest that OspA-vaccination for T helper cell immunity alone is not sufficient to prevent Lyme disease.
抗伯氏疏螺旋体外表面脂蛋白A（OspA）的抗体可保护严重联合免疫缺陷（SCID）小鼠免受随后的蜱传感染或实验性感染。然而，在自然感染的人类、犬、仓鼠和小鼠中几乎检测不到OspA特异性抗体。这很可能是由于从载体传播到宿主的螺旋体上OspA的表达有限。在此，我们测试了对小鼠进行T细胞致敏是否会在感染后诱导产生保护性OspA特异性抗体。结果显示，先前用OspA的单个T辅助细胞肽或跨越整个分子的27种肽的混合物免疫的AKR/N小鼠，在感染低剂量（10³）培养来源的螺旋体7天内，会产生OspA特异性IgM或IgG抗体，包括针对OspA一个主要保护性B细胞表位的抗体。相比之下，相同组的预先致敏小鼠在蜱传感染后40多天未能产生任何可检测到的OspA特异性抗体。所有小鼠，无论其对OspA的T细胞免疫状态或感染方式如何，早在感染后第14天就产生了相似水平的OspC特异性IgM和IgG抗体。尽管出现了保护性抗体，但先前用OspA肽免疫的小鼠中没有一只对实验性感染具有抵抗力。从这些数据可以清楚地看出，与培养来源的螺旋体不同，即使存在预先激活的T辅助细胞，自然传播的病原体在哺乳动物宿主体内也无法以足以诱导B细胞反应的水平表达OspA。再加上OspA特异性抗体主要通过在侵染期间从载体中清除螺旋体起作用这一事实，这些数据表明仅针对T辅助细胞免疫进行OspA疫苗接种不足以预防莱姆病。
