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.

Exposure to radionuclides disseminated by a radiological dispersion device or deposited as fallout after a nuclear power plant accident or detonation of an improvised nuclear device could result in internal contamination of a significant number of individuals. Internalized radionuclides may cause both acute and chronic radiation injury and increase an individual's risk of developing cancer. This damage and risk can be mitigated by the use of decorporation agents that reduce internal contamination. Unfortunately, most effective agents decorporate only a limited range of radionuclides, and some are formulated in ways that would make administration in mass casualty situations challenging. There is a need for new radionuclide decorporation agents, reformulations of existing agents, and/or expansion of the labeled indications for existing treatments. Researchers developing novel or improved decorporation agents should also understand the regulatory pathway for these products. This workshop, the first in nearly half a century to focus exclusively on radionuclide decorporation, brought together researchers and scientific administrators from academia, government and industry as well as senior regulatory affairs officers and U.S. Food and Drug Administration personnel. Meeting participants reviewed recent progress in the development of decorporation agents and contemplated the future of the field.

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.

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Study of the human microbiota has been a centuries-long endeavor, but since the inception of the National Institutes of Health (NIH) Human Microbiome Project in 2007, research has greatly expanded, including the space involving radiation injury. As acute radiation syndrome (ARS) is multisystemic, the microbiome niches across all areas of the body may be affected. This review highlights advances in radiation research examining the effect of irradiation on the microbiome and its potential use as a target for medical countermeasures or biodosimetry approaches, or as a medical countermeasure itself. The authors also address animal model considerations for designing studies, and the potential to use the microbiome as a biomarker to assess radiation exposure and predict outcome. Recent research has shown that the microbiome holds enormous potential for mitigation of radiation injury, in the context of both radiotherapy and radiological/nuclear public health emergencies. Gaps still exist, but the field is moving forward with much promise.