PMID- 37532611 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20230906 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 41 IP - 38 DP - 2023 Aug 31 TI - A Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a tetravalent live attenuated dengue vaccine in adults. PG - 5614-5621 LID - S0264-410X(23)00876-9 [pii] LID - 10.1016/j.vaccine.2023.07.045 [doi] AB - BACKGROUND: Dengue fever is an important public health problem, especially in Asia and South America. A tetravalent live attenuated dengue vaccine was manufactured in India after receipt of vaccine strains from NIAID, NIH, USA. METHODS: This was a Phase 1, double-blind, randomized, placebo-controlled study performed in 60 healthy adults of 18 to 45 years. Participants were randomized 2:1 to receive a single subcutaneous injection of either a tetravalent live attenuated dengue vaccine or placebo. Safety was assessed by unsolicited adverse events (AEs) and solicited reactions through 21 days after vaccination and serious adverse events (SAEs) through the entire study period of 180 days. Dengue viremia was assessed at baseline and on day 9, 11 and 13 post-vaccination using a plaque assay. Immunogenicity was assessed using the plaque reduction neutralization test (PRNT) assay using vaccine-matched wild virus serotypes (DENV 1, DENV 2, DENV 3 and DENV 4) at baseline and on 56-, 84- and 180-days post-vaccination. PRNT assay using circulating wild type DENV 1, DENV 2, DENV 3 and DENV 4 were done on day 1 and day 85 for a subset of 31 participants. RESULTS: 60 participants were randomized to receive dengue vaccine (n = 40) or placebo (n = 20). 23 participants (59 %) showed DENV vaccine viremia post- vaccination for any of the four serotypes with majority on day 9 and day 11. At baseline, all participants were naive by dengue PRNT(50) for all four serotypes in both the study groups except for four in the dengue vaccine group and two in the placebo group. On day 57, the GMTs of neutralizing antibodies ranged from 66.76 (95 % CI 36.63, 121.69) to 293.84 (95 % CI 192.25, 449.11) for all four serotypes in the dengue vaccine group. On day 181 though the titers declined, they still remained much higher than the baseline. The titers in the placebo group did not change after vaccination. Seroconversion through day 85 ranged from 79.5 % for DENV 1 to 100 % for DENV2 while in the placebo group, no participant showed seroconversion through day 85. Similar trends were noted when PRNT was done using wild DENV serotypes in both vaccine and placebo groups. Among solicited reactions, injection site erythema, rash, headache, fatigue, myalgia and arthralgia were reported more frequently in the vaccine group than placebo group. All solicited reactions were of grade 1 or grade 2 severity and completely resolved. One unrelated serious adverse event was reported in the vaccine group. CONCLUSION: A single dose of dengue vaccine was safe and well tolerated in adults. The vaccine was highly immunogenic with trivalent or tetravalent seroconversion and seropositivity in most of the participants. The study was funded by Serum Institute of India Pvt. Ltd., Pune, India. CLINICALTRIALS: gov: NCT04035278. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Gunale, Bhagwat AU - Gunale B AD - Serum Institute of India Pvt. Ltd., Pune, India. FAU - Farinola, Nicholas AU - Farinola N AD - CMAX Clinical Research Pty. Ltd., Adelaide, Australia. FAU - Yeolekar, Leena AU - Yeolekar L AD - Serum Institute of India Pvt. Ltd., Pune, India. FAU - Shrivastava, Shubham AU - Shrivastava S AD - Interactive Research School for Health Affairs (IRSHA), Pune, India. FAU - Girgis, Hanna AU - Girgis H AD - PPD, 3900 Paramount Pkwy, Morrisville, NC 27560, USA. FAU - Poonawalla, Cyrus S AU - Poonawalla CS AD - Serum Institute of India Pvt. Ltd., Pune, India. FAU - Dhere, Rajeev M AU - Dhere RM AD - Serum Institute of India Pvt. Ltd., Pune, India. FAU - Arankalle, Vidya AU - Arankalle V AD - Interactive Research School for Health Affairs (IRSHA), Pune, India. FAU - Chandra Mishra, Akhilesh AU - Chandra Mishra A AD - Interactive Research School for Health Affairs (IRSHA), Pune, India. FAU - Mehla, Rajeev AU - Mehla R AD - Serum Institute of India Pvt. Ltd., Pune, India. FAU - Kulkarni, Prasad S AU - Kulkarni PS AD - Serum Institute of India Pvt. Ltd., Pune, India. Electronic address: drpsk@seruminstitute.com. LA - eng SI - ClinicalTrials.gov/NCT04035278 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230731 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Dengue Vaccines) RN - 0 (Antibodies, Viral) RN - 0 (Vaccines, Combined) RN - 0 (Vaccines, Attenuated) RN - 0 (Antibodies, Neutralizing) SB - IM MH - Humans MH - Adult MH - *Dengue/prevention & control MH - *Dengue Vaccines MH - Antibodies, Viral MH - Vaccines, Combined MH - Viremia MH - India MH - Vaccines, Attenuated MH - Antibodies, Neutralizing MH - Double-Blind Method MH - Immunogenicity, Vaccine OTO - NOTNLM OT - Adults OT - Dengue vaccine OT - Immunogenicity OT - Phase 1 OT - Safety COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [CSP is the chairman and managing director of Serum Institute of India Pvt. Ltd, which is the manufacturer of the study vaccine. PSK, BG, LY, RM, RMD are employed by Serum Institute of India Pvt. Ltd.]. EDAT- 2023/08/03 01:06 MHDA- 2023/08/28 06:43 CRDT- 2023/08/02 21:53 PHST- 2023/01/31 00:00 [received] PHST- 2023/06/05 00:00 [revised] PHST- 2023/07/23 00:00 [accepted] PHST- 2023/08/28 06:43 [medline] PHST- 2023/08/03 01:06 [pubmed] PHST- 2023/08/02 21:53 [entrez] AID - S0264-410X(23)00876-9 [pii] AID - 10.1016/j.vaccine.2023.07.045 [doi] PST - ppublish SO - Vaccine. 2023 Aug 31;41(38):5614-5621. doi: 10.1016/j.vaccine.2023.07.045. Epub 2023 Jul 31.