HIV patients can be vaccinated against TB

Results show a whole cell vaccine works

Tuberculosis is the world's leading cause of death from HIV infection in most parts of the world, but other than a TB vaccine given to infants, little has been done to prevent the spread of TB in this population.

Now researchers have shown that a multiple-dose series of Mycobacterium vaccae given to HIV-infected adults with childhood Bacille Calmette-Guerin (BCG) provides safe and significant protection against tuberculosis.1

The new TB vaccine could reduce tuberculosis infection by 40% in some countries, says Ford von Reyn, MD, professor of medicine and director of the DarDar International Programs for the section on infectious disease and international health at Dartmouth Medical School in Hanover, NH.

"It's a major step forward," he says.

The TB virus can't keep ahead of the vaccine the way it can become resistant to some antibiotic treatments, von Reyn notes.

"A vaccine could be effective against drug-sensitive TB as well as drug resistant TB, so you won't have the problems inherent with antibiotics designed to treat TB," he explains.

"Additional studies will need to be done to see if this would be effective in people without HIV," he adds.

This new vaccine will play a role in helping to prevent TB/HIV coinfection, and it will provide a preventive treatment for some HIV patients who have had a positive TB skin test.

"The TB vaccine given to infants was thought to be effective only for the first 10 to 15 years of life, and there were no data on whether it protects against TB in people with HIV," he says.

Risk to infants

The existing infant TB vaccine has definite risks for infants with HIV infection, so public health officials and researchers launched a major international effort to develop a new TB vaccine, von Reyn notes.

"Our interest was in developing a vaccine that would be safe and effective for adults who were HIV positive and living in a TB endemic country," he says.

Investigators followed an approach based on two premises: "One is the demonstration of killed wholesale vaccines in the 1930s, showing they were effective in preventing TB," von Reyn explains. "Second are the accumulated epidemiological and clinical trials showing that protection against TB is achieved by either having natural infection of mycobacteria of any type or using a vaccine that contains the whole live or whole killed antigen."

So researchers wanted a vaccine that would be safe and still have many antigens, he adds.

A killed whole vaccine fit that bill.

Vaccine trials involving the Mycobacterium vaccae began in the mid-1990s, and the National Institutes of Health (NIH) provided funding for phase III studies involving people living with HIV in a TB endemic country.

"We started the trial in 2001, screened 5,000 people, entered 2,000 in a one to one trial design that was double-blind and followed by a safety board," von Reyn says. "In 2008 we were instructed to stop the trial because the vaccine was shown to be effective."

This was the first new TB vaccine to be shown effective in people, although a number of other TB vaccines are in the clinical trial pipeline, he says.

"It will be another five to 10 years before any other TB vaccine product completes a phase III efficacy trial," von Reyn predicts.

Eros Global TB Foundation of Rockville, MD, has work underway to develop a method to produce this vaccine and scale up production, von Reyn says.

"We're hopeful that work will be completed sometime this year," he says.

The new TB vaccine could be made available in the United States, although it's only been studied in people with HIV in countries with high rates of TB.

"The risk of tuberculosis is sufficiently low in the U.S., so it's not likely it will be a general recommendation for anyone living here," von Reyn says. "It's also true that people living in the U.S. would not have had the BCG vaccine at birth, and the study's results were dependent on their having had the first vaccine."

The new TB vaccine works as a booster, and it would require evaluation for any group that is different from the population studied.

Reference

  1. von Reyn CF, Mtei L, Arbeit RD, et al. Prevention of tuberculosis in Bacille Calmette-Guerin-primed, HIV-infected adults boosted with an activated whole-cell mycobacterial vaccine. AIDS. 2010;24(5):675-685.