Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates
| Autor: | B. Charmie Godornes, Nikhat Parveen, Lorenzo Giacani, Arturo Centurion-Lara, Austin M. Haynes, Mark C. Fernandez, Rui-Li Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
purl.org/pe-repo/ocde/ford#3.03.05 [https]
syphilis TprK Fluorescent Antibody Technique Gene Expression tp0897 gene bacterial vaccine Mass Spectrometry immune response disease burden Epitopes Mice 0302 clinical medicine live vaccine 030212 general & internal medicine Immunity Cellular Attenuated vaccine Treponema biology quantitative analysis Tp0435 Antibodies Bacterial Recombinant Proteins Bacterial vaccine Infectious Diseases priority journal Bacterial Vaccines microscopy Molecular Medicine tprK gene Rabbits bacterial gene purl.org/pe-repo/ocde/ford#1.06.03 [https] 030231 tropical medicine animal experiment Porins Enzyme-Linked Immunosorbent Assay purl.org/pe-repo/ocde/ford#3.03.08 [https] immunization Article reverse transcription polymerase chain reaction 03 medical and health sciences Antigen Bacterial Proteins Immunity peptide vaccine Animals controlled study Syphilis Treponema pallidum Borrelia burgdorferi Antigens Bacterial nonhuman General Veterinary General Immunology and Microbiology tp0435 gene Public Health Environmental and Occupational Health biology.organism_classification bacterial strain Virology Immunization Peptide vaccine gene expression bacteria New Zealand White (rabbit) Peptides |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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