Researchers at Colorado State University report that two new vaccines show promise in preventing tuberculosis in animals.
While not currently as effective as the BCG vaccine, developed in the 1950s and commonly used in Europe, with further development the new vaccines may offer long-term immunity, according to a report by a Colorado State team published in the June issue of the journal Infection and Immunity.
The vaccines have the potential to supplement BCG, believed to lose effectiveness over a period of time, and unlike BCG do not produce positive skin tests for TB in vaccinated individuals.
Ian Orme, professor of microbiology at Colorado State and head of the 10-person team that evaluated the substances, said the vaccines, one developed at Colorado State and the other by the Merck Co., use entirely different approaches to fight tuberculosis.
BCG isn’t used in the United States because until recently, U.S. medical authorities expected TB to be eradicated early in the next century. Instead, the disease has become the leading bacterial killer in the world, causing 10 million new cases and 3 million deaths each year.
Since 1992 Orme and his colleagues have not only pursued their own basic research interests, but with support from a grant from the National Institutes of Health have operated a TB vaccine screening program that has examined dozens of experimental vaccines, including the two reported on this month.
The vaccines described in the Infection and Immunity article work in a different fashion than BCG, which triggers an immune response using weakened bovine tuberculosis bacilli.
The Colorado State vaccine, developed over the past several years by a team led by Orme, uses specific proteins isolated from the tuberculosis bacterium. When mixed with interleukin-2, a protein known to boost the immune system, and added to a carrier called an adjuvant that also helps boost immunity, the vaccine simulates a TB infection and generates a specific type of lymphocyte needed to combat TB infections, Orme said.
The Merck Research Laboratories vaccine, meanwhile, uses a segment of DNA from Mycobacterium tuberculosis that encodes and produces a specific protein that also is involved in immunity to TB. This same approach, using a DNA sequence from a bacterium or virus to stimulate immunity, has produced other promising vaccines for influenza and Lyme disease, Orme said.
As for the TB vaccines, "both vaccines tested at Colorado State give long-term survival against virulent infection that would normally kill animals in a few weeks," Orme said. "Both also prevent tissue destruction and actual disintegration of lung tissues seen in people with active TB."
While not at present as effective as BCG in animal models, Orme thinks either or both vaccines may eventually prove effective in supplementing BCG. Used principally outside of the United States, BCG is given to small children, but evidence suggests immunity wears off.
"Judging from the results of clinical trials in India and elsewhere, we’re pretty certain that by the age of 15 or 16, BCG isn’t working," Orme said. "Accordingly, I think we should be looking upon these new vaccines as a boosting mechanism and not merely as a replacement for BCG."
A major breakthrough of both vaccines tested at Colorado State is that, unlike the BCG vaccine, they don’t trigger a positive reaction to the skin test commonly used to determine if an individual actually has TB.
"With these vaccines, a skin test is still possible," Orme said. "Both the Colorado State and Merck formulations do not induce a skin test reaction if given alone (i.e., without BCG)."
In the United States, virulent, sometimes drug-resistant strains have developed among the homeless, AIDS sufferers and prison populations, and the speed and ease of travel makes tuberculosis a national as well as global problem, Orme said.
The Colorado State researchers conclude in the Infection and Immunity article that their findings "provide optimism that development of nonliving vaccines which can generate long-lived immunity approaching that conferred by the BCG vaccine is a feasible goal." However, Orme warned, the effort will be long-term.
"I will be involved in advising clinicians on setting up these trials, but it will be my children who will finish them," he said. "It may take as many as 25 to 50 years to find out how effective these vaccines are."