Vanderbilt investigators have cracked one of clinical medicine’s enduring mysteries and it is the tuberculosis vaccine. The current TB vaccine known as known as BCG (bacille Calmette-Guérin) no longer prevents the bacterial lung infection that kills more than 1.7 million people worldwide every year but it is still 80 percent effective against “disseminated TB” (TB infection in many parts of the body) in early childhood. BCG was made by weakening (attenuating) a strain of bacteria that causes tuberculosis in cows and that genetically is 98 percent identical to the human TB germ.
Kernodle and colleagues found that the TB vaccine has acquired some traits that make it less effective in evoking a sustained immune response. When they take away these traits, the TB vaccine induces stronger immune responses in mice.
In the current studies, first author Lakshmi Sadagopal, PhD, research instructor of Medicine, vaccinated mice with a modified BCG (genetically changed in three ways to reduce or eliminate the production of several antioxidants) and examined the immune response in the days following vaccination and later with a “challenge” dose of BCG. She found that, compared to BCG, the modified BCG induced greater cytokine (immune regulatory factor) production during the early phase of the immune response, more CD8 cell-killing T cells at the peak of the primary response, and more CD4 helper T cells during the memory phase. Modified BCG also produced greater recall immune responses and was eliminated better by the vaccinated host animal than the parent BCG vaccine, which might correlate with improved safety in humans.
The Aeras Global TB Vaccine Foundation has licensed the modification technology developed by Kernodle and colleagues.