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
De La Barrera, R.
JournalThe American journal of tropical medicine and hygiene
PublisherAmerican Society of Tropical Medicine and Hygiene
MetadataShow full item record
AbstractDengue 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 (£ 4.5% after DPIV+AS03B; £ 2.9% after placebo), with no obvious differences across groups. Within 28 D following each dose, the frequency of unsolicited AEs after DPIV+AS03B appeared higher for three-dose (0–1–6 M) than two-dose (0–1 M and 0–3 M) regimens. No serious AEs were considered related to vaccination, and no potential immune-mediated diseases were reported during the study. All three schedules were well tolerated. Both primary immunogenicity objectives were demonstrated. The 0–3 M and 0–1–6 M regimens were more immunogenic than the 0–1 M regimen.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85087858285&doi=10.4269%2fajtmh.19-0738&partnerID=40&md5=6b836582892e89455b6e8daeffb305f0; http://hdl.handle.net/10713/13372