Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine.

Abstract

SummaryBorrelia burgdo~feri, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdo~feri 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. burgdotferi 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.T he spirochetal agent of Lyme disease, Borrelia burgdooCeri is transmitted by Ixodes ticks. In unfed nymphal ticks, spirochetes are found in the gut (l). During tick feeding, the bacteria disseminate to the salivary glands and infect the vertebrate host (2-4). A vaccine based on B. burgdo~ri outer surface protein (Osp) A which protects mice from infection is currently being tested in human trials (5-7). Here we examine the expression of OspA on spirochetes within engorging nymphs and relate OspA expression to protection afforded by OspA antibody. Materials and MethodsMice. Pathogen-free C3H/HeN (C3H) mice were purchased from the National Institutes of Health (Bethesda, MD). Maintenance and Infection of Ticks. Ixodes dammini (also known as L scapularis)were derived from a colony in its second generation from field-collected adults, and were free of inherited infection. Larvae were allowed to engorge on CD-1 mice that had been infected 2 wk previously by the bites of three to five nymphal I. dammini containing the N40 strain of B. burgdotferi.Engorged larvae were collected, held in mesh-covered plaster of paris containing vials, and were allowed to molt at 95% relative humidity at 21~ The infected nymphs were held under the same conditions before their use in experiments, usually within 2 mo of molting. Antibody Staining of OspA-expressing Spirochetes in NymphalTicks. Guts and salivary glands were dissected out of nymphs and prepared for antibody staining as previously described (2). mAb CIII.78, which binds to a COOH-t...

Artificial‐infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease

“…However, the previous finding that a fraction of experimentally challenged AKR/N mice with high levels of OspC-specific Ab was able to resolve infection [20] and that IS from tick-or needle-infected mice prevent subsequent infection in naive recipients [4,5] suggested that inherent spirochetal defense mechanisms can be breached by more-potent and/or morewell-timed Ab responses. This has been most convincingly documented for Ab to OspA and OspC [10,16,20]. These two lipoproteins are known to be differentially expressed on spirochetes in the vector and mammalian hosts [9,14].…”

“…In fact, it was found that the pattern of osp gene expression in B. burgdorferi dramatically changes depending on the microenvironment and that some osp genes even cease expression in mammals. The latter is the case for ospA, which is dominantly expressed in spirochetes harbored in the gut of unfed ticks, but not in those seeding the vertebrate host [8][9][10][11]. In contrast, expression of other osp genes, e.g.…”

“…Thus it is surprising that not only Ab (including OspC-, pG-, DpbA-and p35/37-specific Ab) that accumulate during natural infection but also Ab (such as OspAspecific Ab) that are hardly, if at all, detectable have the potential to protect mice against subsequent challenge [6,10,13,[16][17][18]. The fact that OspA-specific Ab, which block transmission of spirochetes by targeting and killing B. burgdorferi in the midgut of feeding ticks [10], are generated exclusively under artificial conditions emphasizes the notion that "efficient vaccines may need additional antigenic stimuli not available during natural infection" [1].…”

“…The fact that OspA-specific Ab, which block transmission of spirochetes by targeting and killing B. burgdorferi in the midgut of feeding ticks [10], are generated exclusively under artificial conditions emphasizes the notion that "efficient vaccines may need additional antigenic stimuli not available during natural infection" [1]. On the basis of such studies, a monovalent vaccine, consisting of the OspA lipoprotein, was developed [16] and shown to be efficacious in humans [19].…”

Biology of Infection with Borrelia burgdorferi

“…The population of spirochetes expands [156][157][158] and their protein synthesis alters [49,99,122,159,160]. Then, spirochetes migrate from the midgut to the salivary glands, allowing transmission into a new host.…”