American Journal of Tropical Medicine and Hygiene
Published online March 28, 2016 , doi: 10.4269/ajtmh.15-0659 2016 15-0659
OPEN ACCESS ARTICLE
Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children
Veerachai Watanaveeradej, Sriluck Simasathien, Mammen P. Mammen Jr., Ananda Nisalak,
Elodie Tournay, Phirangkul Kerdpaich, Rudiwilai Samakoses, Robert J. Putnak, Robert V. Gibbons, In-Kyu Yoon, Richard G. Jarman, Rafael De La Barrera, Philippe Moris, Kenneth H. Eckels, Stephen J. Thomas* and Bruce L. Innis
Author Affiliations
Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand; Department of Virology, United States Army Medical Component–Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand; GSK Vaccines, Rixensart, Belgium; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland; Dengue Vaccine Initiative, International Vaccine Institute, Seoul, Republic of Korea; Pilot BioProduction Facility, Translational Medicine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland; GSK Vaccines, Philadelphia, Pennsylvania
Abstract
We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1–4 waned during the 1–3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response.