Journal article
Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells
Science translational medicine, Vol.7(310), pp.310ra167-310ra167
10/21/2015
DOI: 10.1126/scitranslmed.aac5477
PMID: 26491077
Abstract
There is currently no clinically effective vaccine against leishmaniasis because of poor understanding of the antigens that elicit dominant T cell immunity. Using proteomics and cellular immunology, we identified a dominant naturally processed peptide (PEPCK335-351) derived from Leishmania glycosomal phosphoenolpyruvate carboxykinase (PEPCK). PEPCK was conserved in all pathogenic Leishmania, expressed in glycosomes of promastigotes and amastigotes, and elicited strong CD4(+) T cell responses in infected mice and humans. I-A(b)-PEPCK335-351 tetramer identified protective Leishmania-specific CD4(+) T cells at a clonal level, which comprised similar to 20% of all Leishmania-reactive CD4(+) T cells at the peak of infection. PEPCK335-351-specific CD4(+) T cells were oligoclonal in their T cell receptor usage, produced polyfunctional cytokines (interleukin-2, interferon-gamma and tumor necrosis factor), and underwent expansion, effector activities, contraction, and stable maintenance after lesion resolution. Vaccination with PEPCK peptide, DNA expressing full-length PEPCK, or rPEPCK induced strong durable cross-species protection in both resistant and susceptible mice. The effectiveness and durability of protection in vaccinated mice support the development of a broadly cross-species protective vaccine against different forms of leishmaniasis by targeting PEPCK.
Details
- Title: Subtitle
- Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells
- Creators
- Zhirong Mou - University of Manitoba [Winnipeg]Jintao Li - University of ManitobaThouraya Boussoffara - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of InfectionHiroyuki Kishi - University of ToyamaHiroshi Hamana - University of ToyamaPeyman Ezzati - University of Manitoba [Winnipeg]Chuanmin Hu - Army Medical UniversityWeijing Yi - Army Medical UniversityDong Liu - University of ManitobaForough Khadem - University of Manitoba [Winnipeg]Ifeoma Okwor - University of Manitoba [Winnipeg]Ping Jia - University of ManitobaKiyomi Shitaoka - University of ToyamaShufeng Wang - Army Medical UniversityMomar Ndao - McGill University = Université McGill [Montréal, Canada]Christine Petersen - University of Iowa [Iowa City]Jianping Chen - Sichuan UniversitySima Rafati - Molecular Immunology and Vaccine Research LaboratoryHechmi Louzir - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of InfectionAtsushi Muraguchi - University of ToyamaJohn A Wilkins - University of Manitoba [Winnipeg]Jude E Uzonna - University of Manitoba [Winnipeg]
- Resource Type
- Journal article
- Publication Details
- Science translational medicine, Vol.7(310), pp.310ra167-310ra167
- DOI
- 10.1126/scitranslmed.aac5477
- PMID
- 26491077
- NLM abbreviation
- Sci Transl Med
- ISSN
- 1946-6234
- eISSN
- 1946-6242
- Publisher
- American Association for the Advancement of Science
- Grant note
- DOI: 10.13039/100008794, name: Research Manitoba; DOI: 10.13039/501100000024, name: Canadian Institutes for Health Research, award: MOP 114923; DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 30872466; name: Manitoba Institute of Child Health
- Language
- English
- Date published
- 10/21/2015
- Academic Unit
- Epidemiology; Internal Medicine
- Record Identifier
- 9983995049302771
Metrics
12 Record Views