A Vaccine for Leprosy

Identifying Mycobacterium leprae Antigens

Armadillo used for Leprosy research. Photo courtesy of Leprosy Research Support at Colorado State University. http://www.cvmbs.colostate.edu/mip/leprosy/globalleprosy3.html

The genome of M.leprae has been sequenced, however, M.leprae still cannot be cultivated without contamination or association with other organisms. Before completion of the sequence of M.leprae, the only highly purified bacilli originated from infected armadillo tissues, which caused difficulty because certain secreted proteins were lost upon purification of the bacilli from the armadillos. New approaches to identifying genes from completed M.leprae genome sequences are being applied using standard bioinformatics tools that can identify proteins with special features like unique or shared amino acid sequence homologies with proteins of M.tuberculosis or other mycobacteria, and the presence of specialized peptide signatures suggesting their cellular location and possible secretion across the cell membrane (Scollard et. al). Proteins of interest can be prioritized based on potential B-cell and T-cell epitopes. Then the proteins selected for further study can be purified as recombinant proteins for an endless supply of the protein for vaccine research.

Once a DNA vaccine is injected, it produces a protein. At the National Hansen’s Disease Programs Lab, they are currently working with three different proteins, M.leprae antigen 85a, 85b, and 85c. They have been looking into DNA vaccines as an approach to studying may types of proteins that can possibly be used in vaccines, and this particular complex of proteins have been shown in tuberculosis. The proteins are prepared as DNA vaccines and injected into animals like mice. (No human subject studies are currently being conducted). From the two experiments run thus far, antigen 85c seems to have the best efficacy against leprosy infection. Leprosy infection is measured in mice by observation of the footpad. A gene is purified and then put into the mice, then they are exposed to M.leprae. In an unvaccinated animal, there is a small growth in the footpad that indicates infection. In experimental animals, you can test whether the vaccine has slowed or stopped the growth in the footpad of the mouse.

The Future of Leprosy Vaccine Research and Treatment

The number of new leprosy cases identified annually worldwide has probably not changed over the last twenty years, though the number of registered cases has declined as a result of improved treatment and removal from registries. Elimination of an infectious disease such as leprosy requires a highly effective vaccine. Global elimination of leprosy has been the goal of laboratory research and world health organizations for almost twenty years. The current primary intervention for leprosy eradication is early diagnosis in order to attempt to interrupt transmission with treatment as early as possible. Still, this leaves major implications for the treatment of asymptomatic leprosy patients.

There has been much progress in the field of leprosy vaccine research over the years. The genome of M.leprae has been sequenced. The availability of knockout mice deficient in selected immunologic abilities will enable dissection of the roles of different cytokines and T-cell subsets in response to infection. The armadillo genome has been partially sequenced and is currently in the process of annotation, which will hopefully enable researchers to be able to identify and synthesize immunologically relevant cytokines and probes for use in the animal model.

The Laboratory Research Branch of the National Hansen’s Disease Programs remarks, “In addition to newly available search algorithms for genes of interest, new vehicles for delivery of protein antigens have been identified from research on recombinant DNA over the last 20 years. Much of this technology is being used to create vaccines to be administered in concert with BCG, either as recombinant BCG overexperssing one or more antigenic proteins or in a prime-boost scenario where antigen is given first in an adjuvant (priming) and then followed by BCG vaccination to boost the initial response” (Scollard et al.). Dr. Tom Gillis says that it would be a real achievement to improve on current tuberculosis vaccines, and find one that is better able to protect against both infections (leprosy and tuberculosis).

Kiyana Harris, Class of 2007, kjharris@stanford.edu
Stanford University
Parasites & Pestilence: Infectious Public Health Challenges
Prof. D. Scott Smith, ssmith@stanford.edu