Abstract
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).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6351-6359 |
| Number of pages | 9 |
| Journal | Vaccine |
| Volume | 33 |
| Issue number | 46 |
| DOIs | |
| State | Published - Nov 17 2015 |
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Keywords
- Clinical trial
- Dose titration
- Immunogenicity
- Live attenuated tetravalent dengue vaccine
- Multiple administration
- Recombinant chimeric dengue vaccine
- Safety
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
- Molecular Medicine
Cite this
Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults : A Phase 1b randomized study. / Rupp, Richard; Luckasen, Gary Joseph; Kirstein, Judith Lee; Osorio, Jorge E.; Santangelo, Joseph D.; Raanan, Marsha; Smith, Mary Kathryn; Wallace, Derek; Gordon, Gilad S.; Stinchcomb, Dan T.
In: Vaccine, Vol. 33, No. 46, 17.11.2015, p. 6351-6359.Research output: Contribution to journal › Article
}
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.
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
VL - 33
SP - 6351
EP - 6359
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 46
ER -