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Principal Investigator: Stephen Whitehead
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $16,391
Funding agency: National Institute of Allergy and Infectious Diseases
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 was 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 was 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 occurred 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 received a second dose of tetravalent vaccine and were followed for an additional 6 months. Two different vaccine admixtures, TV003 and TV005 were studied in adults. Other age cohorts only received TV005. The study enrolled 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). Final antibody assays for the year 3 samples were delayed due to COVID-19. Cellular immunity assays are still pending at WRAIR. A manuscript describing the study results (not including the cellular immune responses) has been written and extensively reviewed and is still circulating for final comments. The writing effort was originally coordinated by WRAIR and has not reached completion due to numerous changes in staffing. We are in the process of reclaiming stewardship of the most recent draft manuscript. It is anticipated that the manuscript will be submitted for publication before the end of 2024. Although this was a Phase II study and early data from a Phase III was recently published, the data for this study in Bangkok is still important and includes a number of granular analyses that were not addressed in the larger Phase III efficacy trial.
Terms: <0-11 years old><12 year old><12 years of age><17 year old><17 years of age><21+ years old><4 year old><4 years of age><Acceleration><Active Follow-up><Admixture><Adolescent><Adolescent Youth><Adult><Adult Human><Age><Agreement><Area><Assay><Attenuated><Attenuated Vaccines><Bioassay><Biological Assay><Breakbone Fever Virus><COVID-19><CV-19><Cell Mediated Immunology><Cell-Mediated Immunity><Cellular Immunity><Child><Child Youth><Children (0-21)><Clinical><Clinical Research><Clinical Study><Clinical Trials><Comment><Commentary><Controlled Clinical Trials><Coronavirus Infectious Disease 2019><DENV><DENV vaccine><Data><Data Bases><Databases><Dengue><Dengue Vaccine><Dengue Virus><Dengue fever virus><Dengue virus vaccine><Dengvaxia><Dose><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Editorial Comment><Enrollment><Evaluation><Flavivirus><Funding><Genetic><Goals><Group B Arbovirus><Human><Immune response><Immunity><Immunological response><Individual><Infant><Live-attenuated Vaccine><Manuscripts><Medical Research><Modern Man><NIAID><National Institute of Allergy and Infectious Disease><Orthoflavivirus><Phase><Placebo Control><Process><Program Evaluation><Publications><Published Comment><Publishing><Safety><Sampling><Sampling Studies><Scientific Publication><Serology test><Thailand><Vaccination><Vaccinee><Vaccines><Viewpoint><Viremia><Virus><Work><Writing><active followup><adulthood><age 12 years><age 17 years><age 4 years><age group><ages><antibody assay><antibody based test><antibody test><attenuate><attenuates><cohort><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><data base><efficacy trial><enroll><experience><follow up><follow-up><followed up><followup><four year old><four years of age><host response><immune system response><immunogenicity><immunoresponse><juvenile><juvenile human><kids><live vaccine><live vaccines><phase 2 study><phase II study><placebo controlled><programs><serology assay><seventeen year old><seventeen years of age><twelve year old><twelve years of age><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccine against DENV><vaccine against dengue><vaccine candidate><vaccine candidate against dengue><viraemia><viral sepsis><virusemia><youngster>