Phase 1 Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults in the United States

• Published in: The American journal of tropical medicine and hygiene Vol. 96; no. 6; pp. 1325 - 1337
• Main Authors: Schmidt, Alexander C., Lin, Leyi, Martinez, Luis J., Ruck, Richard C., Eckels, Kenneth H., Collard, Alix, De La Barrera, Rafael, Paolino, Kristopher M., Toussaint, Jean-François, Lepine, Edith, Innis, Bruce L., Jarman, Richard G., Thomas, Stephen J.
• Format: Journal Article
• Language: English
• Published: United States The American Society of Tropical Medicine and Hygiene 07.06.2017
• Subjects: Adjuvants, Immunologic - chemistry; Adolescent; Adult; Alum Compounds - chemistry; Antibodies, Viral - blood; Dengue - immunology; Dengue - prevention & control; Dengue Vaccines - administration & dosage; Dengue Vaccines - therapeutic use; Dengue Virus - isolation & purification; Dose-Response Relationship, Drug; Female; Humans; Male; Single-Blind Method; United States; Vaccination; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - therapeutic use; Young Adult
• ISSN: 0002-9637; 1476-1645; 1476-1645
• DOI: 10.4269/ajtmh.16-0634

The safety and immunogenicity of four formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV), formulated at 1 or 4 μg with aluminum hydroxide (alum) or at 1 μg with an adjuvant system (AS01 E or AS03 B ), were evaluated in a first-time-in-human, placebo-controlled, randomized, observer-blind, phase 1 trial in the continental United States. Two doses of vaccine or placebo were administered intramuscularly 4 weeks apart to 100 healthy adults 18–39 years of age, randomized 1:1:1:1:1 to receive one of four DPIV formulations or saline placebo. The response to a third dose was evaluated in a subset of nine participants remote from primary vaccination. Humoral immunogenicity was assessed using a 50% microneutralization assay. All DPIV formulations were well tolerated. No vaccine-related serious adverse events were observed through 12 months after the second vaccine dose. In all DPIV groups, geometric mean antibody titers peaked at Day 56, waned through 6 months after the second vaccine dose, and then stabilized. In the nine subjects where boosting was evaluated, a strong anamnestic response was observed. These results support continuation of the clinical development of this dengue vaccine candidate (clinicaltrials.gov: NCT01666652).