PMID- 26384447
OWN - NLM
STAT- MEDLINE
DCOM- 20160818
LR  - 20151113
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 33
IP  - 46
DP  - 2015 Nov 17
TI  - Safety and immunogenicity of different doses and schedules of a live attenuated 
      tetravalent dengue vaccine (TDV) in healthy adults: A Phase 1b randomized study.
PG  - 6351-9
LID - S0264-410X(15)01251-7 [pii]
LID - 10.1016/j.vaccine.2015.09.008 [doi]
AB  - INTRODUCTION: A safe, effective dengue vaccine that can simultaneously induce 
      immunity to all four dengue virus serotypes (DENV-1-4) is a public health 
      priority. A chimeric tetravalent dengue vaccine (TDV) based on an attenuated 
      DENV-2 serotype backbone was evaluated in healthy, flavivirus-seronegative 
      adults. METHODS: In this randomized, multicenter, Phase 1b study conducted in the 
      United States, the safety and immunogenicity of TDV were evaluated in 140 
      participants aged 18-45 years in six dosing regimen study groups. Participants 
      were injected subcutaneously on Days 0 and 90; placebo (saline) was injected 
      where appropriate to maintain double blinding. Three different TDV dosages (TDV, 
      a vaccine in which TDV-4 had been increased three-fold, and a one-tenth TDV 
      dose), and single or double dosing were evaluated in one and/or both arms. 
      Primary endpoints were solicited and unsolicited adverse events (AEs) and 
      seroconversion rates to DENV-1-4 at Day 120. RESULTS: The severity of all AEs was 
      generally mild. The most common unsolicited AEs were headache (52%), fatigue 
      (43%) and myalgia (29%). The incidence of injection site pain ranged from 29 to 
      64% and 5 to 52% among study groups after the first and second doses, 
      respectively. At Day 120, the ranges of seroconversion rates among the groups 
      were DEN-1: 84-100%; DEN-2: 96-100%; DEN-3: 83-100%; and DEN-4: 33-77%. More than 
      80% of participants in each group seroconverted to at least three dengue 
      serotypes. Substantial GMT increases from baseline were observed for DEN-1-3 at 
      all time points from Day 30 onward; DEN-4 GMT increases were lower. Increasing 
      TDV-4 slightly increased DEN-4 GMT, did not impact DEN-2 and DEN-3 GMT, but 
      reduced DEN-1 GMT. Neither multiple dosing in both arms, nor one-tenth TDV dosing 
      meaningfully impacted GMT increases relative to TDV. CONCLUSIONS: All TDV doses 
      and dosing schedules were well tolerated and immunogenic in healthy 
      flavivirus-naive adults (ClinicalTrials.gov NCT01511250).
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Rupp, Richard
AU  - Rupp R
AD  - Sealy Center for Vaccine Development, University of Texas Medical Branch at 
      Galveston, Galveston, TX, United States.
FAU - Luckasen, Gary Joseph
AU  - Luckasen GJ
AD  - Medical Center of the Rockies Foundation, University of Colorado Health North 
      Research, Loveland, CO, United States.
FAU - Kirstein, Judith Lee
AU  - Kirstein JL
AD  - Utah Research Team, Advanced Clinical Research, West Jordan, UT, United States.
FAU - Osorio, Jorge E
AU  - Osorio JE
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University 
      of Wisconsin-Madison, Madison, WI, United States; Scientific Affairs and Policy, 
      Takeda Vaccines, Inc., Deerfield, IL, United States.
FAU - Santangelo, Joseph D
AU  - Santangelo JD
AD  - Operations, Takeda Vaccines Pte. Ltd, Singapore, Singapore.
FAU - Raanan, Marsha
AU  - Raanan M
AD  - Statistics, Quantitative Sciences, Takeda Development Center Americas Inc., 
      Deerfield, IL, United States.
FAU - Smith, Mary Kathryn
AU  - Smith MK
AD  - Clinical Testing Laboratory, Takeda Vaccines, Inc., Deerfield, IL, United States.
FAU - Wallace, Derek
AU  - Wallace D
AD  - Clinical Development, Takeda Vaccines Pte. Ltd, Singapore, Singapore.
FAU - Gordon, Gilad S
AU  - Gordon GS
AD  - Orra Group, LLC, Boulder, CO, United States.
FAU - Stinchcomb, Dan T
AU  - Stinchcomb DT
AD  - Scientific Affairs and Policy, Takeda Vaccines, Inc., Deerfield, IL, United 
      States. Electronic address: dan.stinchcomb@takeda.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01511250
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20150915
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Dengue Vaccines)
RN  - 0 (Placebos)
RN  - 0 (Vaccines, Attenuated)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Dengue/*prevention & control
MH  - Dengue Vaccines/administration & dosage/*adverse effects/*immunology
MH  - Double-Blind Method
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - *Immunization Schedule
MH  - Incidence
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Placebos/administration & dosage
MH  - United States
MH  - Vaccines, Attenuated/administration & dosage/adverse effects/immunology
MH  - Young Adult
OTO - NOTNLM
OT  - Clinical trial
OT  - Dose titration
OT  - Immunogenicity
OT  - Live attenuated tetravalent dengue vaccine
OT  - Multiple administration
OT  - Recombinant chimeric dengue vaccine
OT  - Safety
EDAT- 2015/09/20 06:00
MHDA- 2016/08/19 06:00
CRDT- 2015/09/20 06:00
PHST- 2015/06/23 00:00 [received]
PHST- 2015/09/01 00:00 [revised]
PHST- 2015/09/02 00:00 [accepted]
PHST- 2015/09/20 06:00 [entrez]
PHST- 2015/09/20 06:00 [pubmed]
PHST- 2016/08/19 06:00 [medline]
AID - S0264-410X(15)01251-7 [pii]
AID - 10.1016/j.vaccine.2015.09.008 [doi]
PST - ppublish
SO  - Vaccine. 2015 Nov 17;33(46):6351-9. doi: 10.1016/j.vaccine.2015.09.008. Epub 2015 
      Sep 15.