Boosting the TB vaccine

The best available vaccine against tuberculosis isn’t foolproof. The so-called bacille Calmette-Guérin (BCG) vaccine is a live but disabled form of the tuberculosis bacterium itself, Mycobacterium tuberculosis. Unfortunately, the vaccine doesn’t carry enough bacterial proteins to prime the immune systems of all recipients for challenges by the real pathogen. The BCG vaccine leaves a fourth of vaccinated children unprotected and protects even fewer adults.

Stewart T. Cole of the Pasteur Institute in Paris and his colleagues report restoring to the vaccine several M. tuberculosis genes that have been absent. The product elicits a more potent immune response in mice and guinea pigs than does the standard BCG, the researchers report in the May Nature Medicine.

Cole’s team noted that people with TB make extra immune cells of the type called T cells. These bonus cells recognize the protein encoded by the gene dubbed ESAT-6, which is knocked out in the process of making BCG. However, the researchers found that restoring the gene for that protein alone wasn’t enough to strengthen T cell response against TB. Only by also restoring several bacterial genes that seem to work with ESAT-6 did the researchers boost immune responses.

“The aim of ‘classical’ vaccines is to mimic natural infections as closely as possible without causing disease,” says Douglas B. Young of the Imperial College London in the same journal. The modifications to BCG seem to accomplish that, he says.

The advent of antibiotics in the 20th century slashed TB rates in developed countries until the disease began a comeback in the 1980s (SN: 10/21/00, p. 270: ). Worldwide, nearly 3 million people die of TB each year.


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