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 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 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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