Safety and Immunogenicity of the Chikungunya Virus-Like Particle Vaccine (VRC-CHIKVLP059-00-VP) in a Phase 2 Randomized, Multicenter, Placebo Controlled Trial in Healthy Adults
Grace L Chen, Emily E Coates, Sarah H Plummer, Nina Berkowitz, Josephine H Cox, Allison Beck, Cristina Carter, Mark O'Callahan, Ingelise J Gordon, Brenda Larkin, Mark Wolff, Yeycy Donastorg, Nicolas Rosario, Clemente Diaz, Jean William Pape, André Cabie, Bruno Hoen, Jeanine May, Amy Bray, Kimberly A Dowd, Brittanie Brockett, David Gordon, John R Mascola, Barney S Graham, Theodore C Pierson, Julie E Ledgerwood, and the VRC 704 study team
Background: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which has spread in recent decades from Africa and Asia to Europe and the Americas for which there are currently no effective vaccines or therapies. We report the initial findings of a Phase 2 clinical trial of an investigational CHIKV vaccine.
Methods: VRC 704 was a phase 2, randomized, placebo-controlled clinical trial testing the virus-like particle (VLP) vaccine VRC-CHKVLP059-00-VP in healthy adults at six endemic CHIKV sites. Subjects were stratified by age group, 18-40 and 41-60, randomized 1:1 vaccine or placebo to receive two intramuscular (IM) injections 28 days apart, and followed for 72 weeks. The primary study objective was to evaluate safety and tolerability of the vaccine, the secondary objective was to evaluate neutralizing antibody response 4 weeks after the second dose, and the exploratory objective was to assess the incidence of CHIKV infection in vaccine and placebo groups. This trial is registered with ClinicalTrials.gov, NCT02562482.
Results: 400 subjects were enrolled in the study between November 18, 2015 and October 20, 2016 and received either 20 mcg vaccine or placebo at days 0 and 28. All injections were well tolerated, with no serious adverse events related to the study product. At baseline, the geometric mean titers (GMT) of neutralizing antibodies were similar between the vaccine and placebo group. Whereas 4 weeks following second product administration the GMT was greater in the vaccine group (2396.1 vs. 44.4) and the positive response rate was significantly greater in the vaccine group than placebo (99.5% vs. 20.7%, p-value < 0.001).
Conclusion: The evaluated CHIKV VLP vaccine was safe, well-tolerated, and immunogenic in CHIKV endemic regions studied in this trial.