Mycobacterium tuberculosis causes more deaths worldwide than any other infectious disease. Although the current BCG vaccine is effective in preventing meningitis and systemic (miliary) disease in infants, its value in preventing pulmonary disease is imperfect. For this reason, researchers have been trying to make a better vaccine to prevent tuberculosis.
One recent vaccine strategy involves linking two M. tuberculosis antigens (Ag85B and TB10.4) to a novel adjuvant (IC31). Like the CpG motif currently used in the Heplisav-B® vaccine, the IC31 adjuvant stimulates a toll-like receptor 9 (TLR9). Heplisav-B has shown superiority when compared with a hepatitis B vaccine that used an aluminum salt as an adjuvant (Engerix®).
This novel recombinant tuberculosis vaccine was recently tested in a phase 2 study in a highly endemic area in South Africa (Nemes E, Geldenhuys H, Rozot V, et. al. Prevention of M. Tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination. N Engl J of Med. 2018 Jul 12;379(2):138-49. DOI: 10.1056/NEJMoa1714021). To determine whether this novel vaccine worked to prevent tuberculosis infection, 990 adolescents who had previously received the BCG vaccine were inoculated with either H4:IC31 or boosted with another BCG vaccine and tested for the presence of tuberculosis infection using the QuantiFERON-TB Gold In-Tube assay (QFT). This assay determines the interferon response to M. tuberculosis antigens that are not contained in either the BCG vaccine or in the H4:IC31 recombinant vaccine. Researchers posited that a persistently positive QFT test indicated infection with tuberculosis. They found that the efficacy of a booster dose of BCG was 45.4 percent and of the H4:IC31 vaccine, 30.5 percent. These results, while somewhat disappointing, should inform clinical development of new vaccine candidates.