Safety and Immunogenicity of an AS03B-Adjuvanted Inactivated Tetravalent Dengue Virus Vaccine Administered on Varying Schedules to Healthy U.S. Adults: A Phase 1/2 Randomized Study.

Dengue disease and its causative agents, the dengue viruses (DENV-1-4), cause high morbidity in tropical and subtropical regions. We evaluated three dosing regimens of the investigational tetravalent AS03B-adjuvanted dengue-purified inactivated vaccine (DPIV + AS03B). In this phase 1/2, observer-blind, placebo-controlled study (NCT02421367), 140 healthy adults were randomized 1:1:2 to receive DPIV + AS03B according to the following regimens: 0-1 month (M), 0-1-6 M, or 0-3 M. Participants received DPIV + AS03B or placebo at M0, M1, M3, and M6 according to their dosing schedule. Primary objectives were 1) to evaluate the safety of DPIV + AS03B for 28 days (D) after each dose; 2) to demonstrate the added value of a booster dose (0-1-6 M versus 0-1 M) based on neutralizing antibody titers to each DENV type (DENV-1-4) at 28 D after the last dose; and, if this objective was met, 3) to demonstrate the benefit of a longer interval between the first and second doses (0-1 M versus 0-3 M). Adverse events (AEs) within 7 D after vaccination tended to be more frequent after DPIV + AS03B doses than placebo; the number of grade 3 AEs was low (