Enhanced protection against Rickettsia rickettsii infection in C3H/HeN mice by immunization with a combination of a recombinant adhesin rAdr2 and a protein fragment rOmpB-4 derived from outer membrane protein B |
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| Affiliation: | 1. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da-Jie Street, Fengtai, Beijing 100071, China;2. Department of Clinical Laboratory, The 105th Hospital of PLA, Hefei, Anhui 230031, China;1. URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, 27 Bd Jean Moulin, 13385 Marseille, France;1. Hokudai Center for Zoonosis Control in Zambia, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan;2. Department of Disease Control, School of Veterinary Medicine, the University of Zambia, Lusaka, Zambia;3. Africa Center of Excellence for Infectious Diseases of Humans and Animals, The University of Zambia, Lusaka, Zambia;4. Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan;5. Division of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan;6. Central Veterinary Research Institute (CVRI), Ministry of Fisheries and Livestock, Lusaka, Zambia;7. Macha Research Trust, Choma, Zambia;8. Department of National Parks and Wildlife, Ministry of Tourism and Arts, Chilanga, Zambia;9. Division of Collaboration and Education, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan;10. International Collaboration Unit, Hokakido University Research Center for Zoonosis Control, Sapporo, Japan;11. Department of Para-Clinical Studies, School of Veterinary Medicine, the University of Zambia, Lusaka, Zambia;12. Global Virus Network, Baltimore, USA;13. Laboratory of Parasitology, Graduate School of Infectious Diseases, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan;1. Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica;2. Sección de Virología, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica;3. Centro de Investigación en Estructuras Microscópicas, Universidad de Costa Rica, San José, Costa Rica;4. Escuela de Biología, Universidad de Costa Rica, San José, Costa Rica;5. Sección de Entomología Médica, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica;6. Servicio de Patología, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica;1. Department of Pathology, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555-0609, USA;2. Infectious Diseases, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555-0435, USA;3. Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, 301 University Boulevard, Keiller Building, Galveston, TX 77555-0609, USA;1. Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA 30460, United States;2. Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, United States;3. California Division of Communicable Disease Control, California Department of Public Health, Richmond, CA, United States |
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| Abstract: | ![]()
BackgroundTwo surface proteins of Rickettsia rickettsii, outer membrane protein B (OmpB) and adhesion 2 (Adr2), have been recognized as protective antigens. Herein, the immunization with both OmpB and Adr2 was performed in mice so as to explore whether their combination could induce an enhanced immunoprotection against R. rickettsii infection.MethodsC3H/HeN mice were immunized with recombinant protein rAdr2 or/and rOmp-4, a fragment derived from OmpB, and then mice were challenged with R. rickettsii. After which rickettsial loads in mice were measured by quantitative PCR. The specific antibodies in mouse sera were determined by ELISA and antigen-specific cytokines secretion by mouse T cells were analyzed in vitro.ResultsAfter challenge with R. rickettsii, the mice immunized with rAdr2 or/and rOmpB-4 had significant lower rickettsial load in livers, spleens, or lungs compared to PBS mock-immunized mice. Particularly, the load in lungs of mice immunized with both rAdr2 and rOmpB-4 was significantly lower than that with either of them. High levels of specific antibodies were detected in sera from mice immunized with rAdr2 or/and rOmpB-4, but the ratios of specific IgG2a to IgG1 induced by their combination were significantly higher than that by either rAdr2 or rOmpB-4. Following stimulation with rAdr2 or/and rOmpB-4, the INF-γ secreted by CD4+ T cells from infected mice was significantly higher than that by cognate cells from uninfected mice. And the TNF-α secreted by CD4+ or CD8+ T cells from infected mice was markedly greater than that by cognate cells from uninfected mice after stimulation by their combination but not either of them.ConclusionThe combination of rAdr2 and rOmpB-4 conferred an enhanced protection against R. rickettsii infection in mice, which was mainly dependent on a stronger Th1-oriented immunoresponse with greater INF-γ and TNF-α secretion by antigen-specific T cells and specific IgG2a elicited by the combination. |
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| Keywords: | Rocky Mountain spotted fever Outer membrane protein B Adhesin |
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