Active and Passive Immunity againstBorrelia burgdorferiDecorin Binding Protein A (DbpA) Protects against Infection

Abstract

Borrelia burgdorferi, the spirochete that causes Lyme disease, binds decorin, a collagen-associated extracellular matrix proteoglycan found in the skin (the site of entry for the spirochete) and in many other tissues. Two borrelial adhesins that recognize this proteoglycan, decorin binding proteins A and B (DbpA and DbpB, respectively), have recently been identified. Infection of mice by low-dose B. burgdorferi challenge elicited antibodies against DbpA and DbpB that were sustained at high levels, suggesting that these antigens are expressed in vivo. Scanning immunoelectron microscopy showed that DbpA was surface accessible on intact borreliae. Passive administration of DbpA antiserum protected mice from infection following challenge with heterologous B. burgdorferi sensu stricto isolates, even when serum administration was delayed for up to 4 days after challenge. DbpA is the first antigen target identified that is capable of mediating immune resolution of early, localized B. burgdorferi infections. DbpA immunization also protected mice from B. burgdorferi challenge; DbpB immunization was much less effective. DbpA antiserum inhibited in vitro growth of many B. burgdorferi sensu lato isolates of diverse geographic, phylogenetic, and clinical origins. In combination, these findings support a role for DbpA in the immunoprophylaxis of Lyme disease and suggest that DbpA vaccines have the potential to eliminate early-stage B. burgdorferi infections.

TheBorrelia burgdorferiCheY3 response regulator is essential for chemotaxis and completion of its natural infection cycle

“…Many of the individual purified proteins tested as vaccines do not confer complete protection (Hanson et al, 1998;Exner et al, 2000;Hagman et al, 2000;Nogueira et al, 2012;Floden et al, 2013). Passive transfer of serum from mice (or humans) injected with WT bacteria or with certain B. burgdorferi proteins seems to provide limited protection (Fikrig et al, 1994;Barthold et al, 1997;Hanson et al, 1998;Fikrig et al, 2000;Hagman et al, 2000;Floden et al, 2013;Small et al, 2014), suggesting that antibodies can provide protection if generated against critical antigens. Attenuated or killed vaccines have been successful in preventing many bacterial and viral infections (Mc, 1948;Mekalanos, 1994;Jin and Subbarao, 2015), but there are few studies screening non-infectious B. burgdorferi mutants for potential protective abilities.…”

Decorin‐binding adhesins from Borrelia burgdorferi

“…If decorin binding is an early step in pathogenesis, Dbps would be excellent targets for vaccine development. Indeed, vaccine studies using Dbps demonstrated that mice passively or actively vaccinated with DbpA are protected when challenged with pathogenic B. burgdorferi (Hanson et al, 1998).…”

“…After labelling, the grids were washed briefly in three changes of deionized water and negatively stained in 0.5% ammonium molybdate. The samples were examined on a Hitachi HU-11 E transmission electron microscope operated at 75 kV (Hanson et al, 1998).…”

The role of Borrelia burgdorferi outer surface proteins

“…Two borrelial proteins, decorin-binding proteins A and B (DbpA and DbpB), have been shown to bind host decorin (Guo et al, 1995). Decorin is a proteoglycan that FEMS Immunol Med Microbiol 66 (2012) Hagman et al, 1998;Hanson et al, 1998). Both proteins are upregulated on the surface of B. burgdorferi organisms grown at reduced pH and by a temperature shift from 23 to 37°C, which suggests an important role for these proteins in the mammalian environment Revel et al, 2002;Ojaimi et al, 2003).…”