Early OspA immune complex formation in animal models of Lyme disease.

Infection with Borrelia burgdorferi, the cause of Lyme disease, has been accompanied by a puzzling delayed antibody (Ab) response to B. burgdorferi antigens (Ags) including the abundant organism-specific outer surface proteins, such as the 31-kD OspA. In humans the response to nonspecific B. burgdorferi Ags has required 3-6 weeks. The response to OspA has rarely been detected by conventional methodology until months after infection, despite demonstrable T cell reactivity. Tick inoculation and low-dose intradermal inoculation animal models have been characterized by a comparable response to OspA. Using more sensitive biotin-avidin immunoblots and immune complex (IC) dissociation techniques, we demonstrated in humans that Ab to OspA is formed early but may remain at low levels or bound in IC. To see if this was a universal biologic response, animal models were analyzed by these methods. The results with mice, monkeys and rabbits show that IC Ab to OspA may be detected at the onset of infection. The data suggest that these animal models may be used to understand the immune response to B. burgdorferi and the pathogenesis of Lyme disease. With attention to unique B. burgdorferi Ags, these results are likely to have both clinical and diagnostic importance.