Blinding
SECONDARY
Participants will not be randomized because the primary endpoints are safety and immunogenicity, and the groups are defined by pre-existing immunity. To avoid biased assessment of AEs and immunogenicity markers, all study staff except the statistician and one computational biologist will be blinded to the final group assignment of each participant. To narrow the screening pool to potentially flavivirus-seronegative and dengue-seropositive individuals, all participants will receive a short, pre-screening Research Electronic Data Capture (REDCap) survey with questions about travel, residential, and flavivirus exposure history. These will be reviewed by the unblinded study staff, who will recommend individuals for screening to help meet the goal of 15 per group. Unblinded study staff will also provide the laboratory with sample identifying codes that require screening for other flaviviruses.To maintain blinding, the clinical team will keep a password-protected list of participant names with corresponding sample identifying codes, and this list will only be available to the clinical team and unblinded study staff. The laboratory team will receive anonymized samples, generate and interpret the screening antibody data, and create a password-protected document that contains the sample identifying codes and group assignment. This document will only be available to the laboratory team and unblinded study staff. Throughout screening, these two documents will be shared with the statistician who will link participant names to group assignments and provide lists of individuals who are eligible for enrollment based on serology results only. All other eligibility criteria will be evaluated by the clinical team. Routine unblinding of group assignment will occur after all 45 participants have completed study day 57, which is the final day for primary and secondary endpoint assessments. AE assessments between days 58 and 180 are less likely to be influenced by baseline immune status, and immunogenicity assessments at days 90 and 180 focus on antibody waning, which is an exploratory endpoint.