de Silva A M, Telford S R, Brunet L R, Barthold S W, Fikrig E
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA.
J Exp Med. 1996 Jan 1;183(1):271-5. doi: 10.1084/jem.183.1.271.
Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdorferi outer surface protein (Osp) A protects mice from spirochete infection. Here we report on the expression of OspA on spirochetes inside engorging ticks and relate OspA expression to antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were stained by an OspA antibody, whereas in feeding ticks, the majority of spirochetes in the gut and salivary glands did not stain with the antibody. Thus, OspA was not expressed on most spirochetes during transmission from the vector to the vertebrate host. To examine the mechanism of protection afforded by OspA antibody, mice were passively immunized with OspA antibody at different times relative to tick attachment. When OspA antibody was administered to mice before or at the time of tick attachment, spirochetal development events in the vector, such as growth and salivary gland invasion, were blocked and the mice were protected from B. burgdorferi infection. When OspA antibody was administered to mice 48 h after tick attachment, spirochetes persisted in the nymphs and the mice were not protected despite the presence of circulating antibodies in the host as well as in the tick blood meal. Thus, OspA immunity appears to be effective only during a narrow window time at the beginning of the blood meal when antibodies bind to OspA-expressing spirochetes in the tick gut and block transmission from the vector to the host.
莱姆病的螺旋体病原体伯氏疏螺旋体通过硬蜱传播。一种基于伯氏疏螺旋体外表面蛋白(Osp)A的疫苗可保护小鼠免受螺旋体感染。在此,我们报告饱血蜱体内螺旋体上OspA的表达情况,并将OspA表达与抗螺旋体免疫联系起来。未进食若蜱肠道内的螺旋体被OspA抗体染色,而在进食的蜱中,肠道和唾液腺中的大多数螺旋体未被该抗体染色。因此,在从媒介传播到脊椎动物宿主的过程中,大多数螺旋体上不表达OspA。为了研究OspA抗体提供保护的机制,在蜱附着后的不同时间用OspA抗体对小鼠进行被动免疫。当在蜱附着前或附着时给小鼠注射OspA抗体时,媒介中的螺旋体发育事件,如生长和唾液腺侵袭,会被阻断,小鼠可免受伯氏疏螺旋体感染。当在蜱附着48小时后给小鼠注射OspA抗体时,螺旋体在若蜱中持续存在,尽管宿主和蜱血餐中都存在循环抗体,但小鼠仍未得到保护。因此,OspA免疫似乎仅在血餐开始时的一个狭窄窗口期内有效,此时抗体与蜱肠道中表达OspA的螺旋体结合,并阻断从媒介到宿主的传播。