IMMUNOGENICITY OUTCOMES OF A RANDOMIZED, MULTICENTER, INTERVENTIONAL, FIRST-IN-HUMAN, PHASE 1/2A STUDY OF VAC52416 (EXPEC10V), A VACCINE CANDIDATE FOR THE PREVENTION OF INVASIVE ESCHERICHIA COLI DISEASE

Abstract

Intro: The safety, reactogenicity, and immunogenicity of VAC52416 (ExPEC10V), a vaccine candidate to prevent invasive Escherichia coli disease, was assessed in a phase 1/2a study (NCT03819049). Results from Cohort 1 have been presented. Here, we describe the immunogenicity profile of the high dose (selected as optimal in the primary analysis) from Cohort 1. Methods: The observer-blind, active-controlled design included a 28-day screening, vaccination, and follow-up through Day 366. Participants (60–85y) were randomized to a single dose (0.5 mL, intramuscular) of: ExPEC10V-high (n=104), -medium (n=102), or -low (n=104) dose; ExPEC4V (n=52); or pneumococcal 13-valent (PCV13; n=54). Immunogenicity (via electrochemiluminescent based immunoassay [ECL] and multiplex opsonophagocytic assay [MOPA]) was assessed on Days 15, 30, 181, and 366. Findings: The robust immunogenic response to ExPEC10V against all serotypes observed with ECL on Day 15 was maintained on Day 30 (N=310). Responses decreased on Day 181 and Year 1 but remained greater than PCV13. 68.0–99.0% of high-dose ExPEC10V participants exhibited ≥2-fold increase from baseline to Day 15 on the ECL across serotypes. Similarly, MOPA revealed high opsonophagocytic killing activity for all but serotype O8 on Day 15. Excluding O8, 38.0–98.0% of high-dose ExPEC10V participants exhibited ≥2-fold increase on the MOPA on Day 15. The highest response was observed for serotype O2 (Day 15, both assays) and the lowest for serotypes O75 (Day 15, ECL) and O8 (MOPA). ECL and MOPA responses to high-dose ExPEC10V were correlated (excluding O8, Pearson's coefficient range: Day 15=0.54–0.72; Day 30=0.45– 0.71, Day 181=0.44–0.77). Conclusion: These data informed the decision to remove serotype O8 and increase the polysaccharide content for serotype O75 of the vaccine composition to create a high-dose ExPEC9V. ExPEC9V is expected to be highly immunogenic, meriting further study as a vaccine candidate to prevent IED.