Safety, Reactogenicity, Immunogenicity, and Dose Selection of 10-Valent Extraintestinal Pathogenic Escherichia coli Bioconjugate Vaccine (VAC52416) in Adults Aged 60-85 Years in a Randomized, Multicenter, Interventional, First-in-Human, Phase 1/2a Study

Carlos A Fierro; Michal Sarnecki; Joachim Doua; Bart Spiessens; Oscar Go; Todd A Davies; Germie van den Dobbelsteen; Jan Poolman; Darren Abbanat; Wouter Haazen

doi:10.1093/ofid/ofad417

Safety, Reactogenicity, Immunogenicity, and Dose Selection of 10-Valent Extraintestinal Pathogenic Escherichia coli Bioconjugate Vaccine (VAC52416) in Adults Aged 60-85 Years in a Randomized, Multicenter, Interventional, First-in-Human, Phase 1/2a Study

Open Forum Infect Dis. 2023 Aug 11;10(8):ofad417. doi: 10.1093/ofid/ofad417. eCollection 2023 Aug.

Authors

Affiliations

¹ Johnson County Clin-Trials, Lenexa, Kansas, USA.
² Infectious Diseases and Vaccines, Janssen Research and Development, Janssen Vaccines, Bern, Switzerland.
³ Infectious Diseases and Vaccines, Janssen Research and Development, Janssen Pharmaceutica, Beerse, Belgium.
⁴ Janssen Research and Development, Raritan, New Jersey, USA.
⁵ Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V., Leiden, The Netherlands.

Abstract

Background: ExPEC10V is a bioconjugate vaccine containing O-antigen polysaccharides of 10 extraintestinal pathogenic Escherichia coli (ExPEC) serotypes. This phase 1/2a study (NCT03819049) assessed the safety, reactogenicity, and immunogenicity of ExPEC10V (VAC52416) to prevent invasive E coli disease in elderly adults.

Methods: The observer-blind, active-controlled design included a 28-day screening, vaccination, 181-day follow-up, and 1-year follow-up. Participants (60-85 years of age) were randomized to ExPEC10V low dose (antigen dose range, 4-8 µg), ExPEC10V medium dose (4-16 µg), or ExPEC10V high dose (8-16 µg); 4-valent ExPEC vaccine (ExPEC4V); or 13-valent pneumococcal conjugate vaccine (PCV13). The incidence of adverse events (AEs; solicited, day 15; unsolicited, day 30; serious AEs, day 181) and immunogenicity (electrochemiluminescent-based assay [ECL] and multiplex opsonophagocytic assay [MOPA]) were assessed. Optimal ExPEC10V dose was determined from safety data through day 30 and an immunogenicity dose selection algorithm based on day 15 ECL and MOPA results.

Results: A total of 416 participants were included (median age, 64.0 years; 54.8% female). The incidences of solicited local and systemic AEs were, respectively, 44.2% and 39.4% for low-dose, 52.9% and 46.1% for medium-dose, 57.7% and 45.2% for high-dose ExPEC10V, and 74.1% and 48.1% for PCV13. Five serious AEs, not vaccine related, were reported. The ECL revealed a robust antibody response to ExPEC10V through year 1. Opsonophagocytic killing activity was detected against all but serotype O8; this lack of response against serotype O8 was linked to low assay sensitivity. Based on the totality of data, high-dose ExPEC10V was considered optimal.

Conclusions: ExPEC10V was well tolerated and immunogenic in elderly adults against all but serotype O8.

Keywords: E coli; bacteremia; extraintestinal pathogenic E coli; invasive E coli disease; vaccine.