PMID- 31843269 OWN - NLM STAT- MEDLINE DCOM- 20210308 LR - 20210308 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 38 IP - 6 DP - 2020 Feb 5 TI - Safety and immunogenicity of a single dose of a tetravalent dengue vaccine with two different serotype-2 potencies in adults in Singapore: A phase 2, double-blind, randomised, controlled trial. PG - 1513-1519 LID - S0264-410X(19)31615-9 [pii] LID - 10.1016/j.vaccine.2019.11.061 [doi] AB - BACKGROUND: Early formulations of Takeda's tetravalent dengue vaccine candidate (TAK-003) have demonstrated notably higher neutralizing antibody responses against serotype 2 than other serotypes. Here, we assessed the immunogenicity and tolerability in adults living in Singapore of two TAK-003 formulations: an early formulation, referred to as HD-TDV, and a new formulation with 10-fold lower serotype 2 potency, referred to as TDV (NCT02425098). METHODS: Subjects aged 21-45 years were stratified by baseline dengue serostatus and randomised 1:1 to receive a single dose of either HD-TDV or TDV. Immunogenicity was evaluated at Days 15, 30, 90, 180, and 365 post-vaccination as geometric mean titres (GMTs) of neutralising antibodies and seropositivity rates. Viremia was assessed per vaccine strain. Solicited and unsolicited adverse events (AEs) were assessed by severity and causality. RESULTS: Of 351 subjects randomised, 176 received HD-TDV and 175 received TDV. Peak GMTs against all serotypes were observed at Day 30, with highest GMTs against DENV-2 in both groups. In subjects seronegative at baseline, the response to DENV-2 was less dominant with TDV (Day 30 GMTs: 813 for TDV, 10,966 for HD-TDV). In these subjects, DENV-4 seropositivity rates and GMTs were higher with TDV (Day 30 GMTs: 58 for TDV, 21 for HD-TDV; seropositivity rates: 76% for TDV, 60% for HD-TDV). Viremia mainly occurred for TDV-2 in both vaccine groups, with a lower incidence in TDV recipients, and mostly resolved by Day 30. Both vaccine formulations showed an acceptable safety profile with similar overall rates of solicited and unsolicited AEs across vaccine groups. CONCLUSIONS: These results suggest a more balanced immune response with the new formulation TDV compared with the early formulation HD-TDV, particularly in subjects who were seronegative prior to vaccination, and support the choice of the new formulation for the phase 3 efficacy assessment. CI - Copyright (c) 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Tricou, Vianney AU - Tricou V AD - Takeda Pharmaceuticals International AG, Zurich, Switzerland. Electronic address: Vianney.tricou@takeda.com. FAU - Low, Jenny G AU - Low JG AD - Singapore General Hospital, Singapore. FAU - Oh, Helen M AU - Oh HM AD - Changi General Hospital, Singapore. FAU - Leo, Yee-Sin AU - Leo YS AD - National Centre for Infectious Disease NCID, Singapore; Tan Tock Seng Hospital, Singapore. FAU - Kalimuddin, Shirin AU - Kalimuddin S AD - Singapore General Hospital, Singapore. FAU - Wijaya, Limin AU - Wijaya L AD - Singapore General Hospital, Singapore. FAU - Pang, Junxiong AU - Pang J AD - Tan Tock Seng Hospital, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore. FAU - Ling, Li Min AU - Ling LM AD - Tan Tock Seng Hospital, Singapore. FAU - Lee, Tau Hong AU - Lee TH AD - Tan Tock Seng Hospital, Singapore. FAU - Brose, Manja AU - Brose M AD - Takeda Pharmaceuticals International AG, Zurich, Switzerland. FAU - Hutagalung, Yanee AU - Hutagalung Y AD - Takeda Vaccines Pte Ltd, Singapore. FAU - Rauscher, Martina AU - Rauscher M AD - Takeda Pharmaceuticals International AG, Zurich, Switzerland. FAU - Borkowski, Astrid AU - Borkowski A AD - Takeda Pharmaceuticals International AG, Zurich, Switzerland. FAU - Wallace, Derek AU - Wallace D AD - Takeda Vaccines Inc., Cambridge, MA, USA. LA - eng SI - ClinicalTrials.gov/NCT02425098 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191213 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Dengue Vaccines) RN - 0 (Vaccines, Combined) SB - IM MH - Adult MH - Antibodies, Neutralizing/immunology MH - Antibodies, Viral/immunology MH - *Dengue/prevention & control MH - Dengue Vaccines/adverse effects/*immunology MH - Double-Blind Method MH - Humans MH - *Immunogenicity, Vaccine MH - Middle Aged MH - Serogroup MH - Singapore MH - Vaccines, Combined/adverse effects/immunology MH - Young Adult OTO - NOTNLM OT - Dengue vaccine OT - Immunogenicity OT - Safety OT - Seronegative OT - Singapore OT - Vaccine viremia COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [VT, MB, YH, MR, AB and DW are permanent employees of Takeda Vaccines. The institutions of JGL, HMO, YSL, SK, LW, JP, LML, and THL received funds from Takeda Vaccines to support the costs of the trial.]. EDAT- 2019/12/18 06:00 MHDA- 2021/03/09 06:00 CRDT- 2019/12/18 06:00 PHST- 2019/08/13 00:00 [received] PHST- 2019/11/22 00:00 [revised] PHST- 2019/11/25 00:00 [accepted] PHST- 2019/12/18 06:00 [pubmed] PHST- 2021/03/09 06:00 [medline] PHST- 2019/12/18 06:00 [entrez] AID - S0264-410X(19)31615-9 [pii] AID - 10.1016/j.vaccine.2019.11.061 [doi] PST - ppublish SO - Vaccine. 2020 Feb 5;38(6):1513-1519. doi: 10.1016/j.vaccine.2019.11.061. Epub 2019 Dec 13.