DNA vaccines expressing a fusion product of outer surface proteins A and C from Borrelia burgdorferi induce protective antibodies suitable for prophylaxis but Not for resolution of Lyme disease.

DNA vaccines encoding the outer surface protein A (OspA) of Borrelia burgdorferi have been shown to induce protective humoral responses capable of preventing but not curing infection in mice. Subsequent studies showed that an established infection or disease could be resolved by passive transfer of antibodies to OspC. In the present study, DNA vaccines encoding either the OspC antigen alone or fused to OspA and under the transcriptional control of the human elongation factor 1alpha promoter were evaluated for their protective and/or curative potential. In contrast to ospA-containing plasmids, none of the six constructs with ospC alone were immunogenic in vivo, independent of whether they contained promoter or leader sequences from ospA and/or ospC, or alternatively, the signal sequence of the human tissue plasminogen activator. Solely, a DNA vaccine encoding an OspA-OspC fusion product led to expression of the respective polypeptide chain in transfected cells in vitro and to the induction of OspA- and OspC-specific antibodies in vivo. Immune sera raised against the OspA-OspC fusion product conveyed full protection against subsequent infection, most probably via OspA-specific antibodies, but were unable to resolve infection.

Prominent T cell response to a selectively in vivo expressed Borrelia burgdorferi outer surface protein (pG) in patients with Lyme disease.

Diagnosis of Lyme disease by analysis of T cell immune responses in vitro is curtailed by poor correlation between test results and status of infection. This is probably due to the inherent nonspecific activation potential of the causative agent, the spirochete Borrelia burgdorferi, for bystander lymphocytes, in particular via their outer surface lipoproteins. We have now applied a novel protocol to determine specific T cell responses in Lyme disease patients and exclude unrelated cellular responses in vitro. Non-lipidated spirochetal antigens (OspA, OspC and P39) including those selectively expressed in the mammalian host (pG and BapA) were used for antigenic stimulation and autologous dendritic cells served as antigen-presenting cells. The majority of patients with well-defined early and late manifestations of Lyme disease exhibited specific T cell proliferative responses to one or more of the indicated antigens, however at distinct levels. Most notably, among the five antigens tested, pG was specifically recognized by the majority of T cell populations (>70%) - mainly Th1 cells - from patients but not control individuals. These data indicate a causal relationship between B. burgdorferi infection and T cell reactivity to pG, thus making this protein a promising additional diagnostic marker for Lyme disease.