Safety, reactogenicity, and immunogenicity of different doses of 10-valent Extraintestinal Pathogenic Escherichia Coli (ExPEC10V) bioconjugate vaccine (VAC52416) in healthy Japanese adults aged 60-85 years in a randomized, double-blind, phase 1 study.

Aim: This phase 1 study (NCT04306302) evaluated the safety, reactogenicity, and immunogenicity of ExPEC10V (VAC52416) in healthy Japanese adults.

Method: The randomized, double-blind, single-center study included 28-day screening, vaccination (Day 1), 30-day safety and immunogenicity follow-up and 181-day serious adverse events (SAEs) follow-up. Participants (60-85 years) were enrolled in dose-ascending approach and randomized to medium- and high-doses of ExPEC10V (n = 8 in each dose group) and placebo (n = 8). Incidence of adverse events: solicited AEs (until Day 15), unsolicited AEs (until Day 30), SAEs (until Day 181) and immunogenicity (electrochemiluminescent-based assay [ECL] and multiplex opsonophagocytic assay [MOPA]) were assessed on Day 15 and Day 30.

Results: Total of 24 participants were included (median age, 66.5 years; 50.0 % female). Incidence of solicited AEs was 81.3 % (local) and 18.8 % (systemic) for pooled ExPEC10V group (medium-dose ExPEC10V: 75.0 % [local], 12.5 % [systemic]; high-dose ExPEC10V: 87.5 % [local], 25.0 % [systemic]). One SAE, not vaccine-related, was reported in high-dose ExPEC10V group after Day 30, which was resolved during study. The ECL demonstrated increase in binding antibody titers, which was maintained from Day 15 to Day 30. For all serotypes, the geometric mean fold increases from baseline on Day 15 ranged from 2.51 to 10.60 and 1.97-5.23 for medium- and high-dose groups, respectively. The MOPA demonstrated increase in functional antibody responses for all serotypes (except O8) at Day 15 which was maintained from Day 15 to Day 30.

Conclusions: ExPEC10V medium- and high-doses were well tolerated with an acceptable safety profile without any significant safety issues in healthy Japanese participants.