Vaccine for the Infected? New TB Vaccine Clears Important Hurdle


An urgently needed new tuberculosis vaccine cleared a vital step in testing, an important advance at time when one-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 15 issue of the American Journal of Respiratory and Critical Care Medicine. MVA85A is scientific shorthand for Recombinant Modified Vaccinia Ankara expressing Antigen 85A.

“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, McShane and fellow researchers investigated the effects of MVA85A specifically in individuals who had LTBI.

“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. They 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 infections. “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, 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. 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 37.5 degrees C (99.5 degrees 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 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.”


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