DAR-901 vaccine safe, effective against tuberculosis
DAR-901, an inactivated booster vaccine against tuberculosis, induces a humoral and cellular immune response against antigens, has an acceptable safety profile, and is well-tolerated, a new randomized controlled trial shows.
The study involved 59 individuals between the ages of 18 and 65 years and who have received bacille Calmette-Guerin (BCG) immunization. Three cohorts of 16 were randomized to receive three doses of DAR-901 (n=10), saline placebo (n=3) or 2 saline injections followed by a DAR-901 injection (n=3). DAR-901 doses were 0.1, 0.3 and 1 mg for the three cohorts, respectively.
A second phase involving open label cohorts included HIV-negative/interferon-gamma release assay (IGRA)-positive patients (n=5) and HIV-positive subjects (n=6). A 1-mg dose of DAR-901 was administered to all at 0, 2 and 4 months. Primary outcomes of the study were safety and immunogenicity.
All reactions to injection were mild and the most frequent were erythema and induration. In IGRA-negative and IGRA-positive patients, there were no significant differences in erythema (10 vs 12 mm, respectively) and induration (8 vs 12 mm, respectively).
No cutaneous breakdown was observed in HIV-negative patients who received 0.1 or 0.3 mg of DAR-901. Mild desquamation was observed in eight HIV-negative/IGRA-negative patients who received 1 mg of DAR-901, while crusts and vesicles were each observed in one patient.
Median erythema and induration was 10 (4 to 20) and 10 (4 to 16) mm, respectively, at 7 days. For BCG, the corresponding values were 30 (10 to 107) and 38 (15 to 55) mm. No serious adverse events were recorded, and there were no differences in adverse event distribution between those who received DAR-901 and saline placebo.
In patients who received the 1-mg dose of DAR-901, median interferon-gamma (IFN-γ) response predose 3 (173 pg/mL) and postdose 3 (102 pg/mL) were significantly greater than baseline response (52 pg/mL; p=0.005 and p=0.011, respectively). The difference in IFN-γ response at day 56 (87 pg/mL; p=0.05) from baseline showed a trend toward significance.
No significant differences in IFN-γ responses were reported for the 0.1- and 0.3-mg doses of DAR-901.