NDLI: TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia)

Content Provider	PubMed Central
Author	Jayakumar, Asha Castilho, Tiago M. Park, Esther Karen, Goldsmith-pestana Blackwell, Jenefer M. Diane, Mcmahon-pratt
Editor	Buxbaum, Laurence U.
Copyright Year	2011
Abstract	Leishmania (Viannia) are the predominant agents of leishmaniasis in Latin America. Given the fact that leishmaniasis is a zoonosis, eradication is unlikely; a vaccine could provide effective prevention of disease. However, these parasites present a challenge and we do not fully understand what elements of the host immune defense prevent disease. We examined the ability of vaccination to protect against L. (Viannia) infection using the highly immunogenic heterologous prime-boost (DNA-modified vaccinia virus) modality and a single Leishmania antigen (TRYP). Although this mode of vaccination can induce protection against other leishmaniases (cutaneous, visceral), no protection was observed against L. (V.) panamensis. However, we found that if the vaccination was modified and the innate immune response was activated through Toll-like receptor1/2(TLR1/2) during the DNA priming, vaccinated mice were protected. Protection was dependent on CD8 T cells. Vaccinated mice had higher CD8 T cell responses and decreased levels of cytokines known to promote infection. Given the long-term persistence of CD8 T cell memory, these findings are encouraging for vaccine development. Further, these results suggest that modulation of TLR1/2 signaling could improve the efficacy of DNA-based vaccines, especially where CD8 T cell activation is critical, thereby contributing to effective and affordable anti parasitic vaccines.
Related Links	http://dx.doi.org/10.1371/journal.pntd.0001204
Starting Page	1204
File Format	PDF
ISSN	19352735
e-ISSN	19352735
Journal	PLoS Neglected Tropical Diseases
Issue Number	6
Volume Number	5
Language	English
Publisher	Public Library of Science
Publisher Date	2011-06-14
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Public Health, Environmental and Occupational Health Pharmacology, Toxicology and Pharmaceutics

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