| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Burgos, Jasmin Abalos, Rodolfo Lee, John S. Jiang, Ju Day, Nicholas P. J. Dela Cruz, Eduardo Chattopadhyay, Suchismita Tan, Esterlina Blacksell, Stuart D. Richards, Allen L. Paris, Daniel H. Turner, Gareth D. Nawtaisong, Pruksa Lombardini, Eric |
| Description |
Author Affiliation: Paris DH ( Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand); Chattopadhyay S ( Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910); Jiang J ( Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910); Nawtaisong P ( Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand); Lee JS ( Division of Entomology, Walter Reed Army Institute of Research, Silver Spring, MD 20910); Tan E ( Leonard Wood Memorial Institute, Cebu 6000, Philippines); Dela Cruz E ( Leonard Wood Memorial Institute, Cebu 6000, Philippines); Burgos J ( Leonard Wood Memorial Institute, Cebu 6000, Philippines); Abalos R ( Leonard Wood Memorial Institute, Cebu 6000, Philippines); Blacksell SD ( Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand); Lombardini E ( Veterinary Medicine Department, Armed Forces Medical Research Institute of Science, Thanon Yothi, 10400 Bangkok); Turner GD ( Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand); Day NP ( Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand); Richards AL ( Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910) |
| Abstract |
We developed an intradermal (ID) challenge cynomolgus macaque (Macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical Asia, caused by the obligate intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. We investigated scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa, Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus-vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle) for safety, immunogenicity, and efficacy against homologous ID challenge with O. tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars, lymphadenopathy, bacteremia, altered liver function, increased WBC counts, pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses. Vaccinated macaques receiving the DNA plasmid pKarp47 vaccine had significantly increased O. tsutsugamushi-specific, IFN-γ-producing PBMCs (p = 0.04), reduced eschar frequency and bacteremia duration (p ≤ 0.01), delayed bacteremia onset (p < 0.05), reduced circulating bacterial biomass (p = 0.01), and greater reduction of liver transaminase levels (p < 0.03) than controls. This study demonstrates a vaccine-induced immune response capable of conferring sterile immunity against high-dose homologous ID challenge of O. tsutsugamushi in a nonhuman primate model, and it provides insight into cell-mediated immune control of O. tsutsugamushi and dissemination dynamics, highlights the importance of bacteremia indices for evaluation of both natural and vaccine-induced immune responses, and importantly, to our knowledge, has determined the first phenotypic correlates of immune protection in scrub typhus. We conclude that this model is suitable for detailed investigations into vaccine-induced immune responses and correlates of immunity for scrub typhus. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1402244 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-02-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antigens, Bacterial Therapeutic Use Disease Models, Animal Scrub Typhus Prevention & Control Vaccination Vaccines, Dna Animals Immunology Macaca Fascicularis Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
