Bacterial and Parasitic Diseases

Malaria

A candidate vaccine (AMA-1) for malaria has been identified and is being developed by researchers at the BPRC. The World Health Organisation has put clinical evaluation of AMA-1 at a high priority. The vaccine is directed against the blood stage development of the parasite; these are the stages that cause death and morbidity as a result of malaria. Clinical testing of this BPRC vaccine will begin in 2003.

A novel, multi-component candidate malaria vaccine was tested at BPRC to see whether it was effective in primates. A long and expensive development programme, potentially leading to the unnecessary exposure of people to an ineffective vaccine, was halted because the vaccine did not work in primates.

The BPRC has pioneered the establishment of a new monkey model using genetically modified malaria parasites to enable quicker identification and validation of new vaccines and drugs. A form of these parasites has been developed for in vitro cultivation. This has substantially reduced the numbers of monkeys required for experiments.

Two new candidate malaria vaccines have been tested. One vaccine showed serious side effects in primates, although promising results (without any side effects) had been obtained in rodents. The other vaccine showed no side effects. The problems of side effects were solved and both vaccines are now in the pipeline for clinical testing in humans.

A new malaria vaccine candidate, directed against the liver stages of the malaria parasite, was identified and shown to be effective in work done at the BPRC. The vaccine showed no side effects. As a result of these studies this vaccine is being taken forward into clinical trials.

A new monkey model has been developed to test anti-malarial drugs. Using this model it has recently been shown that a new family of anti-malarial drugs is very effective and safe in monkeys. Current research, including testing in monkeys, is aimed at finalising the presentation of the drug (to deliver it as a pill instead of as an injection) to enable clinical testing to begin as soon as possible. The presentation of anti-malarial drugs is a critical problem because in poor countries, where malaria is common, health services cannot deliver the standards of care we are used to in the developed world.

Development of another new potential anti-malarial drug was halted because of undesirable side effects that occurred when the drug was tested in primates

Tuberculosis (TB)

Through the rapid spread of multi-drug resistant (MDR) strains, the currently available antibiotics and medicines to treat TB are becoming outdated. New medicines are urgently required. Vaccination can be an extremely effective and cheap health measure that can transform the quality of life of whole populations. This is presently of especial importance in developing countries.

Animal models of tuberculosis are required to test the efficacy and safety of new vaccines before they can be assessed in the clinic. Recently the BPRC has developed and compared two monkey models of tuberculosis infection. These infection patterns show a very high degree of similarity to the infection patterns seen in human. This means that the monkey models can be used to select among different vaccines and vaccine approaches to help determine which vaccines should be tested in human populations. An X-ray photograph of a human tuberculosis infection. The ribs surrounding infected lungs can clearly be seen.

The development of these monkey models is a vital advance because the testing of tuberculosis vaccines in humans will be a long-term, highly complex undertaking that can be justified only for the most promising candidates. Using these models a new candidate tuberculosis vaccine, made by combining two molecules from the tuberculosis bacterium, has recently given promising results.

These results have paved the way for clinical trials of this combination vaccine, and these trials are now being planned.