In June this year, the Pune-based Serum Institute of India Pvt Limited will begin a Phase II/III vaccine trial for tuberculosis using a novel, recombinant BCG (bacillus Calmette-Guérin) vaccine. The double-blind, placebo-controlled, randomised trial will be carried out on 2,000 adults who have been successfully treated (and cured) for TB. While 1,000 adults will receive the vaccine, the remaining volunteers will receive a placebo. A single dose of the vaccine will be administered and the volunteers will be followed-up for a year. The trial will be conducted in 15-17 centres across India.
The new TB vaccine (VPM1002) that will be tested is based on the BCG vaccine that is currently being used but is more powerful and efficacious as it contains a gene that is better recognised by the immune system.
“Adults who have completed TB treatment will be first screened and enrolled if found eligible 2-4 weeks after completion of TB treatment,” says Dr. Prasad S. Kulkarni, Medical Director at Serum Institute. “Traces of the drugs may be present in the body for two weeks after completion of the treatment. Since the vaccine contains live, weakened bacteria, the drugs can kill them if given earlier than two weeks after completing the treatment.”
The vaccine will be first administered in 200 volunteers and safety of the vaccine will be tested. “If there are no safety concerns then the trial will continue in the remaining 1,800 volunteers,” he says.
The safety of the vaccine has already been tested in two Phase I trials — 80 adults in Germany (2009) and 24 adults in South Africa (2010) — and one Phase 2a trial in South Africa in 2012 in 48 newborn infants who have not been exposed to HIV. “These trials have confirmed the safety of the vaccine and sufficient strengthening of the immune system,” says Umesh Shaligram, Director-R&D, Serum Institute.
The results of the Phase 2a trial in newborns in South Africa published in February this year in the journal Clinical and Vaccine Immunology has confirmed the safety of the vaccine. “The VPM1002 is a safe, well-tolerated, and immunogenic vaccine in newborn infants, confirming results from previous trials in adults,” the paper says.
A Phase 2b trial on 416 newborns who have either been exposed or not exposed to HIV is currently under way in South Africa. “Results of the Phase 2b trial will be known in August-September this year. So far there have been no safety concerns,” Dr. Kulkarni says.
While the currently used BCG vaccine causes BCG-related disease in HIV-positive babies (due to reduced immunity), the recombinant version is expected to be safe in babies exposed to HIV.
Serum Institute is also planning to start next year a Phase III trial in newborns in India.
The recombinant vaccine was developed by a team led by Stefan H.E. Kaufmann, the founding director of the Max Planck Institute for Infection Biology, Berlin. The Max Planck Institute holds the patent and has licensed the vaccine to VPM; VPM, in turn, has out licensed it to Serum Institute.
In February last year Prof. Kaufmann told me: “The vaccine being tested is intended to replace the current BCG vaccine and will be administered to young children to protect them against tuberculosis. Adults may also be able to benefit from it later.”