Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine in Flavivirus-Naive Infants

Veerachai Watanaveeradej Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Sriluck Simasathien Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Ananda Nisalak Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Timothy P. Endy Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Richard G. Jarman Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Bruce L. Innis Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Stephen J. Thomas Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Robert V. Gibbons Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Sumetha Hengprasert Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Rudiwilai Samakoses Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Angkool Kerdpanich Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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David W. Vaughn Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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J. Robert Putnak Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Kenneth H. Eckels Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Rafael De La Barrera Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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Mammen P. Mammen Jr. Department of Pediatrics, Phramongkutklao Hospital (PMK), Bangkok, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand; GlaxoSmithKline Biologicals, King of Prussia, Pennsylvania; GlaxoSmithKline Biologicals, Rixensart, Belgium; GlaxoSmithKline Biologicals, Bangkok, Thailand; Divisions of Viral Diseases and Regulated Activities, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland

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DOI:
https://doi.org/10.4269/ajtmh.2011.10-0501
Volume/Issue:
Volume 85: Issue 2
Page(s):
341–351
Restricted access
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A Phase I/II observer-blind, randomized, controlled trial evaluated the safety and immunogenicity of a dengue virus (DENV) vaccine candidate in healthy Thai infants (aged 12–15 months) without measurable pre-vaccination neutralizing antibodies to DENV and Japanese encephalitis virus. Fifty-one subjects received two doses of either DENV (N = 34; four received 1/10th dose) or control vaccine (N = 17; dose 1, live varicella; dose 2, Haemophilus influenzae type b). After each vaccine dose, adverse events (AEs) were solicited for 21 days, and non-serious AEs were solicited for 30 days; serious AEs (SAEs) were recorded throughout the study. Laboratory safety assessments were performed at 10 and 30 days; neutralizing antibodies were measured at 30 days. The DENV vaccine was well-tolerated without any related SAEs. After the second dose, 85.7% of full-dose DENV vaccinees developed at least trivalent and 53.6% developed tetravalent neutralizing antibodies ≥ 1:10 to DENV (control group = 0%). This vaccine candidate, therefore, warrants continued development in this age group (NCT00322049; clinicaltrials.gov).

Author Notes

*Address correspondence to Mammen P. Mammen Jr., ATTN: Dengue Product Manager, Pharmaceutical Systems Program Management Office, U.S. Army Medical Materiel Development Activity, 1430 Veterans Drive, Fort Detrick, MD 21702. E-mail: mammen.mammen@us.army.mil

Financial support: This work was funded by US Army Medical Research and Materiel Command (Fort Detrick, MD) and GlaxoSmithKline (Rixensart, Belgium).

Authors' addresses: Veerachai Watanaveeradej, Sriluck Simasathien, Rudiwilai Samakoses, and Angkool Kerdpanich, Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand, E-mails: veerachaiw@yahoo.com, ssriluck@hotmail.com, rudiwilai_samakoses@hotmail.com, and akpmk@yahoo.com. Ananda Nisalak, Richard G. Jarman, Stephen J. Thomas, Robert V. Gibbons, and Sumetha Hengprasert, Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mails: ananda.nisalak@afrims.org, richard.jarman@afrims.org, Stephen.thomas@afrims.org, Robert.gibbons@afrims.org, and sumethah@afrims.org. Timothy P. Endy, Infectious Disease Division, Department of Medicine, State University of New York, Upstate Medical University, Syracuse, NY, E-mail: endyt@upstate.edu. Bruce L. Innis and David W. Vaughn, GlaxoSmithKline, King of Prussia, PA, E-mails: bruce.2.innis@gsk.com and david.w.vaughn@gsk.com. J. Robert Putnak, Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, E-mail: robert.putnak@amedd.army.mil. Kenneth H. Eckels and Rafael De La Barrera, Pilot Bioproduction Facility, Division of Regulated Activities, Walter Reed Army Institute of Research, Silver Spring, MD, E-mails: kenneth.eckels@amedd.army.mil and rafael.delabarrera1@us.army.mil. Mammen P. Mammen Jr., ATTN: Dengue Product Manager, Pharmaceutical Systems Program Management Office, U.S. Army Medical Materiel Development Activity, Fort Detrick, MD, E-mail: mammen.mammen@us.army.mil.

Copyright:
©The American Society of Tropical Medicine and Hygiene 2011
Received:
08 Sep 2010
|
Accepted:
02 May 2011
|
Published Online:
01 Aug 2011
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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