Daily Archives: January 29, 2010

Defeating diseases of the developing world: tuberculosis and Chikungunya fever

Helicobacter pylori, the bacterium that causes stomach ulcers and stomach cancer, may also play a protective role against tuberculosis, according to studies in both humans and monkeys by a team from Stanford University, UC Davis, the University of Pittsburgh and Aga Khan University in Pakistan (1).

Scanning electron micrograph of Mycobacterium tuberculosis, courtesy of the CDC Public Health Image Library

One-third of the world’s population is infected with TB, although most infections are latent and only one in ten progress to active disease.

The presence of H. pylori in the stomach may boost immunity to the TB bacterium, Mycobacterium tuberculosis. H. pylori infection is still almost universal in developing countries.

The researchers studied people with latent tuberculosis in California, Pakistan and the Gambia over a two-year period. They found that people who were also infected with H. pylori mounted a stronger immune response against TB and were less likely to advance to clinical tuberculosis than those who were not infected with the stomach bug.

They also carried out complementary studies with cynomolgous macaques at the California National Primate Research Center at UC Davis. Like humans, many monkeys naturally carry H. pylori in their stomachs. This study used tissues and samples from monkeys that had already been infected with tuberculosis for other experiments.

Of 41 monkeys, 30 carried H. pylori and only five of these developed active tuberculosis. Six of 11 monkeys that were negative for H. pylori developed tuberculosis. This finding supports the observations made in the human studies and indicates these monkeys are a good experimental model in which further studies can be performed. Already they plan to test whether experimental infection of H. pylori can protect monkeys from TB, and whether it can enhance the protective effect of immunization with current TB vaccines, which are only partially effective.   If these experiments are successful, they will test a genetically modified H. pylori strain developed by Ondek Biologic Delivery Systems that expresses TB antigens as a possible new and more effective vaccine against TB.

A paper describing the results was published Jan. 20 in the open access journal PloS (Public Library of Science) One. The work was funded by grants from the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation.

Of course TB is only one of many infectious diseases that scientists wish to prevent, and another report this week shows what can be achieved when you have a good animal model for a disease. You may not have heard of Chikungunya fever, but outbreaks of this mosquito transmitted illness have blighted the lives of hundreds of thousands of people in Africa and Asia in recent years.

As yet there is no vaccine available, but this week the National Institute of Allergy and Infectious Diseases (NIAID) announced an important step towards a vaccine for Chikungunya fever (2).  Scientists at the NIAID Vaccine Research Center developed an experimental vaccine that employs non-infectious virus-like particles and found it to confer complete protection against Chikungunya fever in rhesus macaques. Antibody-containing serum from these monkeys also protected immunodeficient mice against otherwise lethal doses of Chikungunya virus.  Clinical trials to evaluate the safety of this vaccine and its ability to prevent Chikungunya fever in humans are now being planned.

Regards

Andy Fell, UC Davis

1) Perry S, de Jong BC, Solnick JV, Sanchez MdlL, Yang S, et al. (2010) Infection with Helicobacter pylori is associated with protection against tuberculosis. PLoS ONE 5(1): e8804. doi:10.1371/journal.pone.0008804

2) Akahata W., Yang Z.-Y, Andersen H., Sun S. et al. “A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection” Nature Medicine Published online: 28 January 2010 doi:10.1038/nm.2105