Diversity of Antibody Responses to Borrelia burgdorferi in Experimentally Infected Beagle Dogs

Baum, Elisabeth; Grosenbaugh, Deborah A.; Barbour, Alan G.

doi:10.1128/cvi.00018-14

Cited by 18 publications

(18 citation statements)

References 46 publications

(64 reference statements)

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“…In each subsequent year of life antibody-titers to Bb increased, but only in animals living in endemic areas, suggesting that reinfections were common, although the infecting Bb strains responsible were not isolated [ 36 ]. Given that the antibody profile in dogs appears to be quite similar to that of humans and mice [ 37 ], studies on naturally infected dogs might provide a good model system of natural infection for future investigation on the potential epidemiological impacts of falling antibody levels.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

et al. 2015

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Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat.

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Section: Discussionmentioning

confidence: 99%

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

et al. 2015

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“…The dog that was C6 antibody positive but negative for B. burgdorferi DNA in skin was interpreted as being infected by B. burgdorferi with falsely negative skin biopsy results, which has been previously described. 2 Each of 14 B. burgdorferi-infected dogs also developed antibodies against OspF and P39, and 13 of the 14 dogs developed antibodies against OspC and SLP. Fewer dogs in this experiment developed low levels of short-lasting antibodies against OspA, which was similar to a previous study.…”

Section: Discussionmentioning

confidence: 99%

“…18 However, care must be taken in attempting indirect comparisons of serological response in different studies, as different derivations of peptides can behave differently. 1,2,16 When the OspF antibody responses in all 36 dogs were compared with those of the C6 peptide, sensitivity and specificity were shown to both be 100%. Because antibodies against the other markers could be induced by either vaccination or infection, the sensitivities and specificities were <100%.…”

Section: Discussionmentioning

confidence: 99%

Multiple antigen target approach using the Accuplex4 BioCD system to detect Borrelia burgdorferi antibodies in experimentally infected and vaccinated dogs

et al. 2015

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Abstract. The primary objective of our study was to optimize detection of serum antibodies to Borrelia burgdorferi using a new commercial automated fluorescence system (Accuplex4 BioCD system, Antech Diagnostics, Lake Success, New York). The system used multiple natural and artificial peptides-outer surface proteins (OspA, OspC, OspF), an outer membrane protein (P39), and a proprietary synthetic peptide (small Lyme peptide [SLP])-and the results were compared with a commercially available enzyme-linked immunosorbent assay that uses a proprietary peptide (C6). Sera from 4 groups were evaluated: dogs vaccinated with 1 of 3 commercially available vaccines (n = 18); dogs infested with adult Ixodes scapularis (black-legged tick; n = 18); dogs previously vaccinated and then infested with I. scapularis (n = 18); and dogs with B. burgdorferi infection that were then vaccinated (n = 14). All of the vaccines evaluated induced OspA responses. However, antibodies against OspF or C6 were not induced in any of the vaccinated dogs. Additionally, the OspF antibodies had 100% sensitivity and specificity when compared to antibodies against C6 peptide. In B. burgdorferi-infected dogs, antibodies against OspC and SLP were detected in serum sooner than antibodies against the other targets. Low levels of antibodies against OspA developed in 6 of 14 B. burgdorferi-infected, unvaccinated dogs and had the shortest duration compared to the other antibodies. Detection of antibody responses to multiple B. burgdorferi targets with this system can be used to help differentiate vaccinated dogs from exposed dogs as well as acute infection from chronic infection.

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“…Second, candidate loci typically are chosen due to their antigenicity or surface exposure, which may not be indicative of an ecologically-relevant gene or even a gene with alleles that vary in their effects on fitness. For example, both the FlaB and OspA proteins are antigenic but have little or no allelic variation within populations and no evidence of positive natural selection has been detected [39,[84][85][86]. Third and most importantly, the candidate gene approach cannot identify the genes relevant to the phenotype under investigation if they are not included in the a priori chosen set of loci.…”

Section: Natural Selectionmentioning

confidence: 99%

Evolution and population genomics of the Lyme borreliosis pathogen, Borrelia burgdorferi

et al. 2015

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Population genomic studies have the potential to address many unresolved questions about microbial pathogens by facilitating the identification of genes underlying ecologically important traits such as novel virulence factors and adaptations to humans or other host species. Additionally, this framework improves estimations of population demography and evolutionary history to accurately reconstruct recent epidemics and identify the molecular and environmental factors that resulted in the outbreak. The Lyme disease bacterium, Borrelia burgdorferi, exemplifies the power and promise of the application of population genomics to microbial pathogens. We discuss here the future of evolutionary studies in B.burgdorferi - focusing on the primary evolutionary forces of horizontal gene transfer, natural selection, and migration - as investigations transition from analyses of single genes to genomes.

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Diversity of Antibody Responses to Borrelia burgdorferi in Experimentally Infected Beagle Dogs

Cited by 18 publications

References 46 publications

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Multiple antigen target approach using the Accuplex4 BioCD system to detect Borrelia burgdorferi antibodies in experimentally infected and vaccinated dogs

Evolution and population genomics of the Lyme borreliosis pathogen, Borrelia burgdorferi

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