about leprosy: leprosy vaccine update
Research at IDRI: update October 2006
Researchers at IDRI (Infectious Disease Research Institute) have announced progress in their quest for a vaccine to prevent leprosy.
According to American Leprosy Missions president, Christopher J. Doyle, “The vaccine project is part of our vision to, one day, achieve a world without leprosy.” The leprosy vaccine project has been generously supported by ALM contributors.
According to recent reports, IDRI has more than fifty “candidate proteins” that may be suitable for use in either a leprosy vaccine or a leprosy “diagnostic kit.”
A “candidate protein” is either identical to, or very similar to, a protein found in the leprosy organism.
“Thus, when we show the immune system this protein,” say researchers, “the immune system identifies it as foreign material and mounts a response against it. Any time you teach the immune system to recognize and attack a part of the leprosy organism (a single protein), the body's chance of ridding the disease entirely is increased dramatically.”
(Note: The leprosy diagnostic kit IDRI intends to develop would be similar to a pregnancy detection kit. Instead of detecting certain hormones in a woman's urine, this kit detects certain factors (immune response proteins induced by leprosy infection) in a drop of blood. It is very simple to use and requires no scientific instruments, thus making it easy to use “in the field.” The drop of blood is placed in an a little indentation in the kit which has certain chemicals in it. Then the blood and chemicals interact with a piece of special paper; the paper will develop a line on it if the person has leprosy. No line means no leprosy.)
Research on the candidate proteins is being conducted at IDRI’s headquarters in Seattle as well as by ALM partners in Brazil and the Philippines.
“The rate at which the IDRI team, together with collaborators, has identified leprosy vaccine candidates is unprecedented,” says Doyle. “This rapid progress should allow IDRI to begin preparing a vaccine for human testing as early as 2007.”
Another unique aspect of the IDRI vaccine approach is that the vaccine will be used to treat, as well as to prevent leprosy. IDRI has extensive experience in using a therapeutic vaccine approach and has just received a $32M grant from the Bill and Melinda Gates Foundation to use this approach to cure another serious infectious disease, leishmaniasis.
(NOTE: A “therapeutic vaccine” is a new concept in immunology. Generally vaccines are given BEFORE you get the disease, then when the body sees the disease it can fight it better.
For a “therapeutic vaccine”, you can get the shot AFTER you are infected by the organism. The vaccine gives a further boost to the immune system and helps or teaches it how to better fight off the infection. This wouldn't be particularly useful if the disease were of short duration (flu) or if the body already knew how to fight it — but when it’s a disease that lasts a long time and gets progressively worse, then it’s a great thing!
Also, this means you don’t have to give 10 million people a vaccine to prevent a thousand cases — you focus on the people who have the disease and don’t give unnecessary shots. Additionally, and almost as importantly, with a vaccine that will ultimately be applied in poor countries, by reducing the number of people needing to get a shot, we will dramatically cut costs and make it more appealing for widespread implementation.)
IDRI is currently conducting work to identify the signs that a person with leprosy has been cured after receiving the extensive regimen of anti-leprosy drugs. Toward this end, IDRI has begun a study in Brazil, involving patients who are enrolled for multi-drug therapy, to examine those patients whose bodies are better able to control leprosy after they are naturally infected. This research will be used to better determine the most effective length of anti-leprosy treatment required, as well as the efficacy of a future vaccination. It is our intent that this research will lead to a therapeutic vaccine for leprosy, relieving disease symptoms in already infected individuals.
For additional information about American Leprosy Missions’ vaccine research, contact Mr. Doyle at amlep@leprosy.org.
Research at IDRI: March, 2006
Diagnostic test: researchers at IDRI have now identified two specific antigens (referred to as ML0405 and ML2331) which, when combined with the existing PGL-1 antibody test, give a significantly greater sensitivity and specificity to the test. These results have been accepted for publication in the scientific journal “Clinical and Vaccine Immunology”. IDRI has begun the process of developing a simple test, using these antigens, that can be mass produced for use in endemic situations. It is expected that initial field studies of such a test could begin later in 2006.
Vaccine: the process of antigen discovery, which yielded the two antigens suitable for a diagnostic test, has also provided several new antigens which could potentially form the basis of a specific vaccine against leprosy. The process of vaccine development is slower and more complex than for the diagnostic test, because of the need to show that the antigens can produce a protective effect in live animals (and later on, in humans, of course). Not only do the best antigens have to be identified, but they have to be injected in the right kind of ‘soup’ (known as an adjuvant), which helps to stimulate the right kind of immune response. Steady progress with this work continues.
May 2005
Thanks to ALM funding, IDRI (Infectious Disease Research Institute) has been able to complete screening of the leprosy bacillus for proteins strongly recognized by the human immune system. We have purified over 50 of these proteins and tested them rigorously for suitability as a leprosy vaccine or diagnostic test. We have now identified the lead candidates:
- 3 proteins that show strong potential to diagnose leprosy
- 5 proteins with potential for development of a leprosy vaccine to protect against disease
This is a very exciting time. The discovery of these proteins represents a unique step forward in the development of an effective vaccine and improved diagnosis of leprosy.
We at IDRI thank you for your continued support to help reach this goal. Click here to read more (PDF).
October 2003
Summary. During the past several months, since receiving ALM funding, we have begun to build the infrastructure for an exhaustive antigen discovery/evaluation program at IDRI. Collaborations have been established, gene cloning has been initiated, and several antigens have been evaluated for diagnostic potential. The goals of the program are:
1. To develop a rapid, sensitive, and specific diagnostic test based on antibody detection. This project will involve identification of M. leprae antigens that, when combined, will be used in a rapid test format to detect early (sub-clinical) as well as clinical cases of leprosy. By taking advantage of bioinformatic and genetic approaches, we have made rapid progress toward this aim.
2. To develop a defined skin test to detect early M. leprae infection. Based on our experience with tuberculosis, we felt that it is quite likely that a sensitive and specific intra-dermal skin test capable of distinguishing M. leprae infection from infection with other mycobacteria can be developed. We are preparing state-of-the art gene libraries to be screened with human
3. To develop a leprosy vaccine. The realistic goal of this project is to develop a vaccine that will complement BCG to provide immunity to leprosy disease. The vaccine will consist of recombinant protein in adjuvant, and be applied in a prime-boost regimen with BCG. Emphasis will be on the development of a therapeutic vaccine, or theracine, but evaluation of prophylactic potential will also be performed.
Scientific Progress. In spite of limited resources, IDRI has made new discoveries likely to change the way leprosy is detected. Significantly, we have discovered and performed limited testing on new diagnostic peptides and proteins. Our studies have so far produced two candidate reagents with strong diagnostic potential for antibody detection in leprosy patients. We will investigate their potential to contribute to the diagnosis of sub-clinical and clinical leprosy using individual patient sera from different endemic areas.
Collaborations: We have made contact with most of the leprosy research community, including Drs. Pat Brennan, Tom Ottenhoff, Robert Modlin, Tom Gillis, James Krahenbuhl, and Professor Warwick Britton. We have held meetings with Drs. Brennan, Ottenhoff, Gillis, Krahenbuhl, and Professor Britton. The most significant collaborations have been with Dr. Brennan, who has supplied M. leprae DNA, purified from armadillo tissue, of consistently high quality which has enabled us to progress rapidly in gene library construction and antigen evaluation. Through Dr. Brennan, we have also accessed the very competent vaccine testing center in Bangkok, where we plan to test new vaccine candidates. Dr Tom Gillis has agreed to supply us with M. leprae DNA, purified from infected nude mouse footpads, to construct additional gene libraries. In addition, Dr. Krahenbuhl has been very helpful in initiating collaboration with Dr. Reece in development of a leprosy mouse ear infection model for vaccine evaluation.
