A Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a tetravalent live attenuated dengue vaccine in adults

• Published in: Vaccine 2023-08, Vol.41 (38), p.5614-5621
• Main Authors: Gunale, Bhagwat, Farinola, Nicholas, Yeolekar, Leena, Shrivastava, Shubham, Girgis, Hanna, Poonawalla, Cyrus S., Dhere, Rajeev M., Arankalle, Vidya, Chandra Mishra, Akhilesh, Mehla, Rajeev, Kulkarni, Prasad S.
• Format: Article
• Language: English
• Subjects: Adults; Adverse events; Age; Antibodies; Arthralgia; Assaying; Attenuation; Dengue fever; Dengue vaccine; Double-blind studies; Erythema; Health care; Hematology; Hepatitis; Immunization; Immunogenicity; Infections; Injection; Laboratories; Myalgia; Neutralization; Pharmacists; Phase 1; Placebos; Plaque assay; Public health; Safety; Seroconversion; Serotypes; Vaccines; Vector-borne diseases; Viremia; Viruses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2023.07.045

•This was a first in human Phase 1, randomized, double blind, placebo controlled study in 60 healthy adults of 18 to 45 years of age in Australia to assess safety and immunogenicity of SII Dengue vaccine.•SII Dengue vaccine was safe and well tolerated with no causally related serious adverse event reported in the study.•More than 69% participants had tetravalent and >15% participants had trivalent seroconversion.•These data support further development of this vaccine in Phase 2/3 clinical trials to assess efficacy, immunogenicity and safety in larger target population. 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 8, 10 and 12 post-vaccination using a plaque assay. Immunogenicity was assessed using the plaque reduction neutralization test (PRNT) assay using vaccine 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 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 PRNT50 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 i