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Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates

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dc.contributor.author Parveen, N.
dc.contributor.author Fernandez, M.C.
dc.contributor.author Haynes, A.M.
dc.contributor.author Zhang, R.-L.
dc.contributor.author Godornes, B.C.
dc.contributor.author Centurion-Lara, A.
dc.contributor.author Giacani, L.
dc.date.accessioned 2019-07-04T17:00:19Z
dc.date.available 2019-07-04T17:00:19Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/6867
dc.description.abstract Background: Syphilis is resurgent in many developed countries and still prevalent in developing nations. Current and future control campaigns would benefit from the development of a vaccine, but although promising vaccine candidates were identified among the putative surface-exposed integral outer membrane proteins of the syphilis spirochete, immunization experiments in the rabbit model using recombinant antigens have failed to fully protect animals upon infectious challenge. We speculated that such recombinant immunogens, purified under denaturing conditions from Escherichia coli prior to immunization might not necessarily harbor their original structure, and hypothesized that enhanced protection would result from performing similar immunization/challenge experiments with native antigens. Methods: To test our hypothesis, we engineered non-infectious Borrelia burgdorferi strains to express the tp0897 (tprK) and tp0435 genes of Treponema pallidum subsp. pallidum and immunized two groups of rabbits by injecting recombinant strains intramuscularly with no adjuvant. TprK is a putative integral outer membrane protein of the syphilis agent, while tp0435 encodes the highly immunogenic T. pallidum 17-kDa lipoprotein, a periplasmic antigen that was also shown on the pathogen surface. Following development of a specific host immune response to these antigens as the result of immunization, animals were challenged by intradermal inoculation of T. pallidum. Cutaneous lesion development was monitored and treponemal burden within lesions were assessed by dark-field microscopy and RT-qPCR, in comparison to control rabbits. Results: Partial protection was observed in rabbits immunized with B. burgdorferi expressing TprK while immunity to Tp0435 was not protective. Analysis of the humoral response to TprK antigen suggested reactivity to conformational epitopes. Conclusions: Immunization with native antigens might not be sufficient to obtain complete protection to infection. Nonetheless we showed that non-infectious B. burgdorferi can be an effective carrier to deliver and elicit a specific host response to T. pallidum antigens to assess the efficacy of syphilis vaccine candidates. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries Vaccine
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject animal experiment en_US
dc.subject Article en_US
dc.subject bacterial gene en_US
dc.subject bacterial strain en_US
dc.subject bacterial vaccine en_US
dc.subject Borrelia burgdorferi en_US
dc.subject controlled study en_US
dc.subject disease burden en_US
dc.subject gene expression en_US
dc.subject immune response en_US
dc.subject immunization en_US
dc.subject live vaccine en_US
dc.subject microscopy en_US
dc.subject New Zealand White (rabbit) en_US
dc.subject nonhuman en_US
dc.subject peptide vaccine en_US
dc.subject priority journal en_US
dc.subject quantitative analysis en_US
dc.subject reverse transcription polymerase chain reaction en_US
dc.subject syphilis en_US
dc.subject Syphilis en_US
dc.subject Tp0435 en_US
dc.subject tp0435 gene en_US
dc.subject tp0897 gene en_US
dc.subject TprK en_US
dc.subject tprK gene en_US
dc.subject Treponema pallidum en_US
dc.title Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.vaccine.2019.02.022
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.03
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.05
dc.relation.issn 1873-2518


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