DbpA, but Not OspA, Is Expressed by Borrelia burgdorferi during Spirochetemia and Is a Target for Protective Antibodies

Abstract

DbpA is a target for antibodies that protect mice against infection by cultured Borrelia burgdorferi. Infected mice exhibit early and sustained humoral responses to DbpA and DbpB, suggesting that these proteins are expressed in vivo. Many antigens expressed in mammals by B. burgdorferi are repressed in vitro at lower growth temperatures, and we have now extended these observations to include DbpA and DbpB. To confirm that the protective antigen DbpA is expressed in vivo and to address the question of its accessibility to antibodies during infection, we examined B. burgdorferi in blood samples from mice following cutaneous inoculation. B. burgdorferi was visualized by dark-field microscopy in plasma samples from spirochetemic mice, and an indirect immunofluorescence assay showed that these spirochetes were DbpA positive and OspA negative. We developed an ex vivo borreliacidal assay to show that hyperimmune antiserum against DbpA, but not OspA, killed these plasma-derived spirochetes, demonstrating that DbpA is accessible to antibodies during this phase of infection. Blood transferred from spirochetemic donor mice readily established B. burgdorferiinfection in naive recipient mice or mice hyperimmunized with OspA, while mice hyperimmunized with DbpA showed significant protection against challenge with host-adapted spirochetes. Antiserum from persistently infected mice had borreliacidal activity against both cultured and plasma-derived spirochetes, and adsorption of this serum with DbpA substantially depleted this killing activity. Our observations show that immunization with DbpA blocks B. burgdorferi dissemination from the site of cutaneous inoculation and suggest that DbpA antibodies may contribute to control of persistent infection.

Evidence of Dbps (decorin binding proteins) among European strains of Borrelia burgdorferi sensu lato and in the immune response of LB patient sera

“…Our data are the ¢rst report regarding immune responses in European patient sera to both Dbp proteins and give indirect evidence of their expression in Borrelia during human infection. The level of reactivity to Dbps that we found, mostly in early LB sera, was not as high as the level obtained with the mouse immune response, which is unanimously claimed to be strong and early against DbpA [3,4] and was lower compared to the high reactivity of p41, p58, p53, p21 OspC and p83^100 [5^8] reported in both early and late LB European human sera. Nevertheless we would like to point out that the reactivity we observed in immunoblots of patient sera in the 20^22 kDa region attributed to OspC and p21, is probably also due to the reactivity of Dbps.…”

“…In the mouse, these adhesins elicit a persistent antibody response which is capable of protecting mice from challenge with homologous and heterologous B. burgdorferi strains [2,3] and there is evidence that both adhesins are expressed in vivo [2]. DbpB has been seen to be less e¡ective than DbpA in inducing a protective immunization in mice [2].…”

The nervous system as ectopic germinal center: CXCL13 and IgG in lyme neuroborreliosis

“…Decorin‐binding protein A (dbpA)24 and Bbk3225, 38 are proteins known to be critical for spirochetal binding to host cells and have been demonstrated to be upregulated during infection 25, 38. Because protein production by the spirochete is likely to affect the antigenic repertoire of the antibodies being produced by the host, we looked for expression of these genes in the tissues of the NHPs.…”

“…To facilitate its survival, B. burgdorferi preferentially expresses specific genes in arthropod vector and vector host which are expressed minimally in the cultured spirochete 22, 23. Two of these genes expressed during murine infection are DbpA24 and BBK32 25. In parallel with spirochetal gene expression, chronic infection stimulates upregulation of several cytokine genes in the host.…”

Evidence for Vaccine Synergy between Borrelia burgdorferi Decorin Binding Protein A and Outer Surface Protein A in the Mouse Model of Lyme Borreliosis

“…Decorin binding protein A (DbpA) is another B. burgdorferi surface-exposed lipoprotein that has shown vaccine efficacy against experimental infection in the mouse model (5,10,13,14). B. burgdorferi continues to express DbpA, but not OspA, after dermal inoculation and remains vulnerable to DbpA antibodies during the early stages of local and disseminating infection in mice (5,14); additionally, DbpA is immunogenic during human Lyme disease (6). OspC (25) and other antigens (1, 11) on mammalian-host-adapted B. burgdorferi also represent potential targets for protective or disease-resolving antibodies.…”