Impact of the Leishmania Genome on Vaccine Development
Jenefer M. Blackwell, Diane McMahon-Pratt and Mary E. Wilson
from: Leishmania: After The Genome (Edited by: Peter J. Myler and Nicolas Fasel). Caister Academic Press, U.K. (2008)
Leishmaniasis affects 12 million people but there are no vaccines in routine use. The genomic sequence of Leishmania is complete, providing a rich source of vaccine candidates. Two recent studies used genome-based approaches to screen for novel vaccine candidates. The first screened 100 randomly selected amastigote-expressed genes as DNA vaccines against L. major infection in mice. Fourteen reproducibly protective novel vaccine candidates were identified; the best was an amastin-like gene with 54 related copies in the genome. Of concern, seven vaccines reproducibly exacerbated disease. This correlated with interleukin-10 production by antigen-driven CD4+CD25+ regulatory T cells. Protection correlated with CD4+ effector T cells producing interferon-γ in the presence of low interleukin-10. The second study used a two-step procedure to identify T cell antigens. Step one was to screen a L. chagasi cDNA library with a pool of sera from visceral leishmaniasis patients. Positive clones were then screened for ability to elicit proliferation and interferon-γ in T cells from immune mice. Six unique clones were identified: glutamine synthetase, a transitional endoplasmic reticulum ATPase, elongation factor 1gamma, kinesin K-39, repetitive protein A2, and a hypothetical conserved protein. The 20 antigens identified in these two studies are being further evaluated for vaccine development read more ...