NEW VACCINE : WEAPON AGAINST BOTH TB, LEPROSY
In many parts of the world, leprosy and tuberculosis live side-by-side.
Worldwide there are approximately 233,000 new cases of leprosy per year, with
nearly all of them occurring where tuberculosis is endemic.
The currently
available century-old vaccine Bacille Calmette-Guerin, or BCG, provides only
partial protection against both tuberculosis and leprosy, so a more potent
vaccine is needed to combat both diseases. UCLA-led research may have found a
stronger weapon against both diseases.
In a study published
in the September issue of the peer-reviewed journal Infection
and Immunity, the researchers found that rBCG30, a recombinant
variant of BCG that overexpresses a highly abundant 30 kDa protein of the
tuberculosis bacterium known as Antigen 85B, is superior to BCG in protecting
against tuberculosis in animal models, and also cross protects against leprosy.
In addition, they found that boosting rBCG30 with the Antigen 85B protein, a
protein also expressed by the leprosy bacillus, provides considerably stronger
protection against leprosy.
"This is the
first study demonstrating that an improved vaccine against tuberculosis also
offers cross-protection against Mycobacterium leprae, the causative agent of
leprosy," said Dr. Marcus A. Horwitz, professor of medicine and
microbiology, immunology and molecular genetics, and the study's senior author.
"That means that this vaccine has promise for better protecting against
both major diseases at the same time.
"It is also the
first study demonstrating that boosting a recombinant BCG vaccine further
improves cross-protection against leprosy," he added.
In one experiment,
mice were immunized with either rBCG30 or the old BCG vaccine, or they were
given a salt solution. Ten weeks later, the mice were injected with live
leprosy bacteria into their footpads and seven months after that, the number of
leprosy bacteria in their footpads was measured. The researchers found that the
mice given BCG or rBCG30 had much fewer leprosy bacteria in their footpads than
the mice given the salt solution. Additionally, mice immunized with rBCG30 had
significantly fewer leprosy bacteria than those vaccinated with BCG.
In a second
experiment, the mice were first immunized with BCG or rBCG30, and then
immunized with a booster vaccine (r30) consisting of the TB bacterium's 30-kDa
Antigen 85B protein in adjuvant -- that is, in a chemical formulation that
enhances the immune response. The group of mice immunized with rBCG30 and
boosted with r30 had no detectable leprosy bacteria in their footpads, in
contrast to groups of mice immunized with all other vaccines tested, including
BCG and rBCG30 alone and BCG boosted with r30.
In other
experiments, the immune responses of the mice were measured after vaccination.
Mice immunized with rBCG30 and boosted with r30 had markedly enhanced immune
responses to the leprosy bacterium's version of the Antigen 85B protein, which
is very similar to the one expressed by the tuberculosis bacillus, compared
with mice immunized with the other vaccines and vaccine combinations.
A Phase 1 human
trial for rBCG30 has proven that it is safe and significantly more effective
than BCG, and it is the only candidate replacement vaccine for BCG tested thus
far to satisfy both of these key clinical criteria. Horwitz noted that this
most recent study, however, was conducted in an animal model of leprosy, so
further study is needed to gauge the effectiveness of the rBCG30 vaccine in
protecting against leprosy in humans. The next step in the research will be to
test the rBCG30 vaccine for efficacy in humans against TB. If it's effective
against TB, then the next step would be to test its effectiveness in humans
against leprosy.
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