A Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a tetravalent live attenuated dengue vaccine in adults.
Adults
Dengue vaccine
Immunogenicity
Phase 1
Safety
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
31 08 2023
31 08 2023
Historique:
received:
31
01
2023
revised:
05
06
2023
accepted:
23
07
2023
medline:
28
8
2023
pubmed:
3
8
2023
entrez:
2
8
2023
Statut:
ppublish
Résumé
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. 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. 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 naïve by dengue PRNT 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. gov: NCT04035278.
Sections du résumé
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 naïve by dengue PRNT
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.
Identifiants
pubmed: 37532611
pii: S0264-410X(23)00876-9
doi: 10.1016/j.vaccine.2023.07.045
pii:
doi:
Substances chimiques
Dengue Vaccines
0
Antibodies, Viral
0
Vaccines, Combined
0
Vaccines, Attenuated
0
Antibodies, Neutralizing
0
Banques de données
ClinicalTrials.gov
['NCT04035278']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5614-5621Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
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.].