Statistics
Since this is a first-in-human study, the number of participants needed to be limited. The sample size was not based on statistical hypothesis testing but was computed to detect AEs with a high incidence rate. Having ten participants per group exposed to PepGNP-Dengue allowed an 80% power of detecting an AE with a true incidence of 7.5% across all exposed participants (LD and HD combined) or 20% within a single dose group. Analysis was by intention-to-treat (ITT) for safety and both ITT and per protocol (PP) for immunogenicity, based on actual results with no missing data imputed.AEs are described with absolute and relative frequencies (%) according to the group to which participants were randomized. Mean, standard deviation (SD), minimum, maximum, median, and quartiles were used for continuous safety laboratory variables. Safety analyses are descriptive only; because of the small sample size, no formal statistical hypotheses were tested.For AIM analyses, results are expressed as relative frequencies (%) of CD8+ T cells co-expressing CD107a+CD25+ and CD137+CD69+ or positive for at least one of the 2 co-marker combinations. Results in unstimulated conditions were subtracted from stimulated results. Change from baseline was defined as the delta post- minus pre-vaccination response. The cut-off for positive response was defined as the mean +2 SD of the DENV-specific AIM+CD8+ T cell response in all volunteers at day 0. A responder was defined as a participant with a positive delta AIM+CD8+ T cell response and a response above the cut-off.For dextramer analyses, results are expressed as the number of CD8+ T cells DENV dextramer positive (D-dextr+)/10For immunological analyses, median and 95% confidence intervals (CI) are presented. Non-parametric intra-group comparisons were conducted using the Friedman test, while inter-group comparisons utilised the Kruskal–Wallis test. Dunn’s multiple comparisons test was employed for comparison with day 0 or at each timepoint. The Fisher’s exact test was used to compare the number of responders. A significance level of 0.05 was set. LD and HD vehicle-GNP participants were pooled in the group vehicle-GNP (n = 6).Demographic, clinical, and safety data were collected and managed using REDCap electronic data capture tools hosted at Unisanté, then analysed with STATA 16 and Excel. Immunogenicity data were analysed with Excel and GraphPrism (version 9.1.0).