Researchers at the Albert Einstein College of Medicine of Yeshiva University, New York, have developed a prototype vaccine against tuberculosis (TB) that works better in animal models than the only TB vaccine now available.
Currently, the only available vaccine—known as Bacille Calmette-Guérin (BCG)— fails to protect adults from TB infection and doesn’t reliably stem the reactivation of pulmonary TB, the disease’s most common form.
“Virtually all efforts to develop a better TB vaccine have focused on ‘boosting’ BCG—modifying it to elicit a stronger immune response in people,” says William Jacobs, Jr, MD, PhD, co-senior author of the paper and a Howard Hughes Medical Institute investigator at Einstein as well as professor of microbiology & immunology and molecular genetics.
“But we feel that tweaking the marginally useful BCG vaccine is the wrong strategy. So we’ve started with virulent M. tuberculosis—the organism that actually causes TB in humans—and are knocking out certain genes to yield a live, attenuated M. tuberculosis strain that still produces a strong immunological response that protects people.”
Einstein researchers discovered a gene in M. tuberculosis, known as secA2, that the TB bacteria rely on to prevent apoptosis, the “cell suicide” that triggers the immune response. The researchers then knocked that gene out of the TB chromosome, creating a weakened mutant strain of the bacterium. When the mutant TB strain was injected into laboratory animals, infected cells underwent apoptosis, eliciting a strong and long-lasting T-cell response against the bacteria.
Since the completion of this study, the Einstein researchers have knocked out an additional gene—with plans to knock out still another—that will make the vaccine safer for human use.