TY - JOUR
T1 - Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults
T2 - A Phase 1b randomized study
AU - Rupp, Richard
AU - Luckasen, Gary Joseph
AU - Kirstein, Judith Lee
AU - Osorio, Jorge E.
AU - Santangelo, Joseph D.
AU - Raanan, Marsha
AU - Smith, Mary Kathryn
AU - Wallace, Derek
AU - Gordon, Gilad S.
AU - Stinchcomb, Dan T.
N1 - Funding Information:
Editorial assistance with preparation of the manuscript was provided by Samantha Santangelo, PhD, funded by Takeda Vaccines Inc. The authors are grateful to Michele Hurliman, Matt Dreitz and Cynthia Thomson for protocol development, implementation and study site liaison and management. We also wish to thank John Arguello, Corina Casey, Kelly Moss, Shawn Silengo, and Bethany Swope for clinical assays and Vianney Tricou for assistance with preparation of the graphs and for collating the authors’ comments during the writing process.
PY - 2015/11/17
Y1 - 2015/11/17
N2 - 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).
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).
KW - Clinical trial
KW - Dose titration
KW - Immunogenicity
KW - Live attenuated tetravalent dengue vaccine
KW - Multiple administration
KW - Recombinant chimeric dengue vaccine
KW - Safety
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U2 - 10.1016/j.vaccine.2015.09.008
DO - 10.1016/j.vaccine.2015.09.008
M3 - Article
C2 - 26384447
AN - SCOPUS:84946606951
VL - 33
SP - 6351
EP - 6359
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 46
ER -