New TB vaccine shows promise in HIV infection

An innovative vaccine against tuberculosis has shown promise in persons with HIV, researchers from Dartmouth Medical School and the National Public Health Institute of Finland report in the Nov. 7 issue of the journal AIDS.

An international team led by DMS infectious disease expert Dr. C. Fordham von Reyn, professor of medicine, found that the new booster, a killed vaccine, enhanced the TB immunity of HIV patients. Their weakened immune systems make the current TB vaccine, which is a live vaccine, more risky.

In most countries where TB is widespread, children generally receive a vaccine made from live Mycobacterium bovis, Bacille Calmette-Guerin (BCG) that has been used to reduce the risk of TB for more than half century. Despite the widespread use of BCG, TB has been growing dramatically in the world, fueled by the increased susceptibility of HIV-infected people to TB.

TB remains the largest cause of death worldwide from any single infectious disease, according to the National Institute of Allergy and Infectious Diseases, which calls it “the major attributable cause of death” in HIV/AIDS patients.

“Since there is no evidence that the current BCG vaccine protects patients with HIV against TB, we have been working on a new strategy to immunize persons with HIV against TB, safely and effectively,” said von Reyn.

In a “back to the future” approach, the investigators revived a strategy used successfully prior to BCG: administration of killed vaccines against TB. The DMS-led team dusted off the concept to employ a multiple dose series of a contemporary killed mycobacterial vaccine to prevent TB in a particularly vulnerable and ever growing group of patients.

The study was done in Finland where BCG vaccine is routinely administered at birth. A cohort of 39 HIV patients, mainly men, were divided into two groups to receive a five-dose course of the killed vaccine, Mycobacterium vaccae, or a control vaccine for Hepatitis B. Parallel studies were also conducted on HIV- negative subjects.

“The multiple-dose course of the inactivated vaccine boosted immunity against TB both in those with HIV and those without TB,” von Reyn said. “The vaccine was also safe and did not adversely affect the patients’ underlying HIV infection.”

The study served as the basis for a large-scale trial Dartmouth researchers have been conducting since 2001 in Dar es Salaam, Tanzania with Muhimbili Hospital Medical Center. The five-year $3 million NIH funded study is the only efficacy trial of a new TB vaccine currently under way in the world. The Tanzania trial will enroll more than 2000 HIV-infected patients to determine if the boosted immunity detected in the Finnish study actually reduces the risk of tuberculosis among HIV infected people in Tanzania at high risk of the disease.

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First author of the article is Dr. Jenni Vuola of the National Public Health Institute of Finland. Co-authors include Dr. Matti Ristola from Helsinki University Central Hospital, Dr. Bernard Cole, associate professor of community and family medicine at DMS and Susan Tvaroha at DMS. The M. vaccae vaccine is produced by SR Pharma in London.

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