New TB vaccine clears important hurdle
8 May 2009
An urgently needed new tuberculosis vaccine cleared a vital step in
testing, an important advance at time when a third of the world’s
population is believed to be have latent tuberculosis infection (LTBI),
which, when re-activated, can cause full-blown disease.
The results of the Phase I trial of a leading new TB vaccine, MVA85A,
appeared in the April 15th issue of the American Journal of
Respiratory and Critical Care Medicine. MVA85A is scientific
shorthand for Recombinant Modified Vaccinia Ankara expressing Antigen
“A more effective vaccine regimen than the currently available
bacillus Calmette-Guérin (BCG) would have a major impact on the global
TB burden, and ultimately, will be the most efficient way to control
this pandemic,” wrote principal investigator, Helen McShane, MD, PhD,
reader in vaccinology and Wellcome senior fellow at the University of
Oxford’s Jenner Institute in England.
One-third of the world’s population is latently infected with M.
tuberculosis. Any new TB vaccine must be developed with this huge
reservoir of infection in mind, as latent infection may decrease the
therapeutic value of new vaccines or worsen vaccine-related adverse
events. With this in mind, Dr McShane and fellow researchers
investigated the effects of MVA85A specifically in individuals who had
“While BCG gives good protection against severe forms of TB… it does
not provide adequate protection against adult pulmonary TB,” noted Hazel
Dockrell, PhD, and Ying Zhang, PhD, in an accompanying editorial.
went on to note that one of the primary issues with developing new
vaccines is the critical public health challenge of carrying out
vaccination campaigns in settings where individuals may have latent
“There have been concerns that induction of a strong immune
response in infected individuals might produce immunopathology and that
it would not be possible to exclude such individuals from vaccination in
settings such as Africa,” they wrote.
To test the safety of the MVA85A vaccine in that vulnerable
population, Dr McShane and colleagues recruited 12 individuals who were
confirmed to have LTBI and did not have other complicating factors, such
as HIV or hepatitis for a year-long study.
“We had two aims in mind with this study,” the researchers explained.
“First, we wanted to demonstrate that MVA85A was safe in individuals
with LTBI, and to ensure we were not inducing any immunopathology with
this vaccine. Secondly, we wanted to investigate the immunogenicity of
this vaccine in individuals with LTBI and compare that with previous
findings in individuals who had been BCG vaccinated.”
The investigators found the vaccine was safe and did not induce any
immunopathology in this group, and also that the vaccine was as
immunogenic in this group, as in the BCG-vaccinated individuals. Dr.
McShane calls these results “very important in the further development
of this vaccine.”
Each patient was vaccinated with the MVA85A vaccine and followed for
12 months. The researchers used blood tests and diary cards to identify
any adverse reactions to the vaccine and monitored serum inflammatory
markers to monitor for any signs of immunopathology.
None of the subjects reported fever of more that 37.5º C (99.5 º F),
the only previously recorded objective symptom associated with MVA85A
vaccination. All other symptoms were subjective. Mild local side effects
at the site of vaccination were common, and mild systemic side
effects — such as headache and fatigue — occurred in up to 50 percent of
subjects, but these all resolved spontaneously. There were no
significant increases in serum inflammatory markers.
Interestingly, vaccination with MVA85A in LTBI-infected individuals
seemed to produce a powerful/potent immune response comparable to
previous trials in BCG vaccinated people. It had previously been
demonstrated that the combined immunogenicity in people vaccinated with
both BCG and MVA85A is significantly greater than in those vaccinated
with BCG alone.
“This is the first subunit TB vaccine to enter clinical trials in M.
tuberculosis-infected subjects since Robert Koch experimented with
his ‘remedy’ of culture filtrate protein in 1890 with devastating
consequence,” said Dr McShane. “We can happily report that the MVA85A
had no such ill consequence and represents a great hope for the future
fight against global TB. We are looking forward to the next phase of
research that will continue to assess the safety, while further
evaluating its efficacy in preventing new infections.”
“The results of this trial are very important, as they suggest MVA85A
is safe and highly immunogenic in people who are infected with M.
tuberculosis,” she concluded. “Further, larger trials are needed in TB
endemic areas to assess the efficacy of this vaccine against the
development of TB disease, but these results are very encouraging and
justify the further development of this vaccine.”
Bookmark this page