The only vaccine currently available against tuberculosis, Bacillus Calmette Guérin (BCG), is not equally effective against all types of tuberculosis. A clinical trial in South Africa has now shown that the new vaccine candidate VPM1002, decades in development, is equally safe for newborns with and without HIV exposure and has fewer side effects compared to BCG.
First used 100 years ago, the BCG vaccine against the disease contains attenuated pathogens of cattle tuberculosis. “We know that BCG can prevent so-called tuberculous meningitis and miliary tuberculosis in infants with a 75 to 86 percent effectiveness rate. But this is not the case for the most common form of the disease, pulmonary tuberculosis, in all age groups. Here, BCG is only insufficiently effective,” explained Max Planck researcher Stefan H.E. Kaufmann, who developed the vaccine with his team.
Since the 1990s, the infection biologist and his team have been working on an improved next-generation vaccine, called VPM1002. To achieve this, the researchers genetically modified the attenuated BCG vaccine strain so that immune cells can better recognise the pathogens. “We developed VPM1002 in no small part to combine increased safety with improved efficacy for immunocompromised children,” Kaufmann said.
Vaccine candidate VPM1002 is safe
The group of immunocompromised children includes, for example, HIV-exposed infants born to HIV-positive mothers. In a clinical trial in South Africa, researchers compared VPM1002 with BCG in HIV-exposed and non-HIV-exposed newborns. The study examined both the safety and the immunogenicity associated with the formation of immune cells and immunostimulatory proteins. The study, published in Lancet Infectious Diseases, concluded that VPM1002 is safe in both HIV-exposed and non-HIV-exposed newborns, has fewer side effects than BCG, and elicits a similar immune response.
In the randomised phase II double-blind study in South Africa, 416 eligible newborns were randomly selected and vaccinated before day 12 of life. 312 of them received VPM1002, and 104 received the BCG vaccine. As the study showed, VPM1002 triggered fewer vaccine-related adverse reactions than BCG. This was true for reactions occurring at the injection site, such as scarring and abscess formation, as well as enlargement of lymph nodes. This finding is important because local and regional reactions after vaccination are among the limitations of the BCG vaccine, Kaufmann points out.
Newborns with or without HIV exposure showed similar immunogenicity with both vaccines, though starting at six weeks of age, the BCG-triggered immune response was greater than in even younger infants.
Phase III study investigates protection
“Studies such as those described here examine a vaccine’s immunogenicity, but not its protection. For the latter, we have already developed a larger phase III clinical trial and have successfully enrolled mothers with their newborns to participate. Now the clock is ticking,” Kaufmann said. He expects initial results showing whether VPM1002 can provide comparable or better protection than existing BCG vaccines in about three years. In addition, VPM1002 vaccine is currently in two other phase III clinical trials in India for protection against tuberculosis, which expected to be completed in 2023 and 2024.
Source: Max-Planck-Gesellschaft
