CAP:Evaluation of a Dengue Vaccine in Adults with Preexisting Flavivirus Immunity

National Institute Of Allergy And Infectious Diseases

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Abstract

A detailed statement of work was prepared to describe the activities to be carried out by the AFRIMS group in Bangkok, Thailand. An Interagency Agreement (A-AI-12-051-0000-0000) was executed between NIAID and the U.S. Army Medical Research and Materiel Command and became effective on 09-01-2012. This agreement governs the activities between NIAID and AFRIMS and was initially funded by the NIAID Concept Acceleration Program (CAP) and the Division of Clinical research. CAP funding will be used to support this clinical trial, including the required serological assays, viremia assays, and other clinical activities associated with the evaluation of the tetravalent dengue vaccine. The purpose of this project is to evaluate a live attenuated tetravalent DENV vaccine candidate with regard to safety, tolerability, genetic stability, and immunogenicity in humans, and to study the host's immune response to these viruses. Vaccination will occur in an age de-escalation manner, beginning with adults, followed by adolescents, older children, and finally younger children. Six months after primary vaccination, adult subjects will receive a second dose of tetravalent vaccine and will be followed for an additional 6 months. Two different vaccine admixtures, TV003 and TV005 will be studied in adults. Other age cohorts will only receive TV005. The study will enroll 294 subjects in a double-blind, placebo-controlled clinical trial. Adult cohort received dose 1 on Dec 6, 2014 and dose 2 on June 6, 2015. Adolescent cohort (13 - 17 years old) dosed Mar 2015 (3-YR follow-up ended Mar 2018) Older child cohort (5 - 12 years old) dosed Aug 2015 (3-YR follow-up ended Aug 2018) Younger child cohort (1 - 4 years old) dosed Nov 2015 (3-YR follow-up ended Nov 2018) Currently, all subjects have completed the follow-up phase of the study. The follow-up period was initially set for 1 year, but the US FDA has asked that we follow-up individuals for a period of 3 years (based on the Sanofi-Pasteur Dengvaxia experience). This extended follow-up period also delayed the planned unblinding of the study. Since the last vaccinees was enrolled in the study on Nov 7, 2015, the 3-year follow-up period ended in November 2018. During 2019, the safety databases were locked and the study has been unblinded. All remaining study samples were transferred to the US (LVD and WRAIR) in Apr 2019. Final antibody assays for the year 3 samples need to be completed but have been delayed due to COVID-19. Cellular immunity assays are still pending at WRAIR due to the COVID-19 interruption.