University of Cambridge  

 Genetics and Infection Laboratory 


From genomes to vaccines for leishmaniasis

We are using genomic approaches to identify novel vaccine candidates for leishmaniasis. Microarray analysis of expression profiles of 1843 unique genes has provided 263 novel vaccine candidates specifically upregulated in amastigotes. Using DNA vaccination, we have tested 100 genes singly and in pools and identified 14 novel reproducibly protective antigens and 6 novel reproducibly exacerbatory antitens. We are analysing immune responses associated with protection or exacerbation, and have demonstrated that the ratio of IFN-gamma:IL10, rather than absolute levels of IFN-γ produced, provides the best correlate of protective immunity. Protective antigens are being retested in prime/boost vaccine protocols (DNA plus attenuated Salmonella typhimurium or vaccinia virus) to improve efficacy and establish a vaccine protocol suitable for use in humans.

Retrospective bioinformatic analysis of vaccine efficacy for the 100 antigens will inform us as to future strategies for rapid development of vaccines based on pathogen sequence data. Our ultimate goal is to produce composite vaccines from our most protective antigens and to take these vaccines into human phase I/phase II trials. On the way we will test our vaccines in primates in experimental studies, and in a field trial for vaccination against leishmaniasis in dogs which are the major reservoir host for visceral leishmaniasis, in Brazil.

Project Leader
Jenefer Blackwell

Gabriel Grimaldi, Fiocruz Institute, Brazil
Selma Jeronimo, Universidade Federal do Rio Grande do Norte, Natal
Diane McMahon-Pratt, Yale University, USA
Mary Wilson, University of Iowa, USA
Genetic susceptibility
to infectious disease
From genome
to vaccines for
Last updated on the 11th August 2004
Maintained by Richard Francis.