The following is a summary of “Efficacy and immunogenicity following dengue virus-1 human challenge after a tetravalent prime-boost dengue vaccine regimen: an open-label, phase 1 trial,” published in the April 2024 issue of Infectious Disease by Lyke et al.
Dengue vaccine development requires reliable testing methods, such as Dengue human infection models (DHIMs), to identify promising candidates before large-scale trials.
Researchers conducted a retrospective study assessing the safety and effectiveness of a dengue vaccine using a DHIM.
They conducted a phase 1 open-label trial at the University of Maryland with healthy adults (aged 18-50) divided into two groups. One previously vaccinated with a specific dengue regimen (vaccine group) and unvaccinated individuals with no prior exposure to flaviviruses (control group). Vaccinated participants with detectable dengue-specific antibodies and unvaccinated controls received a dengue virus-1 challenge via inoculation strain 45AZ5 in the deltoid region 27–65 months following booster dosing. Participants were monitored for 4-16 days following the challenge, measuring viral RNA levels and recording any reported side effects. The study’s primary endpoints are safety (through side effects) and efficacy (ability to prevent viral RNA detection) of the vaccination regimen.
The result showed 10 participants in January 2021, with 6 (60%) in the vaccinated group and 4 (40%) in the control group. Dengue virus-1 RNA was detected by daily PCR in 9 out of 10 participants (90%). Among the infected, 5 out of 6 (83%) were in the vaccinated group, and all 4 (100%) were in the control group. The average time for detectable RNAaemia appeared earlier in the vaccinated group (day 5, SD 1.0) than in the control group (day 8, SD 1.5). The difference between the two groups was statistically significant (95% CI 1.1-4.9; P=0.007). A shorter RNAaemia duration was observed in the vaccinated group (8.2 days) compared to controls (10.5 days), although the findings did not reach statistical significance (95% CI -0.08 to 4.68; P=0.056). Mild-to-moderate symptoms (90% of leukopenia) (89% of those with symptoms) and elevated liver enzymes (78% of symptomatic) were commonly observed. Notably, severe AEs were only seen in the vaccinated group, including high fever (50% of vaccinated), headache (17%), and transient grade 4 elevation in AST levels (17%). Additionally, 0 mortality rate was reported.
Investigators concluded that participants exhibited susceptibility to dengue-1 infection before vaccination, suggesting the need for further research on vaccine efficacy.
Source: thelancet.com/journals/laninf/article/PIIS1473-3099(24)00100-2/abstract#%20
