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 Infectious Diseases, vol. 10, pp. ofad417

Abstract

Background: 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.

Authors 10

1. Carlos A. Fierro

   Johnson County Clin-Trials (United States)

   Affiliation as printed

   Johnson County Clin-Trials , Lenexa, Kansas , USA

2. Michal Sarnecki corresponding

   Janssen (Switzerland)

   Affiliation as printed

   Infectious Diseases and Vaccines, Janssen Research and Development, Janssen Vaccines , Bern , Switzerland

3. Joachim Doua

   Janssen (Belgium)

   Affiliation as printed

   Infectious Diseases and Vaccines, Janssen Research and Development, Janssen Pharmaceutica , Beerse , Belgium

4. Bart Spiessens

   Janssen (Belgium)

   Affiliation as printed

   Infectious Diseases and Vaccines, Janssen Research and Development, Janssen Pharmaceutica , Beerse , Belgium

5. Oscar T. Go

   Janssen Research & Development (United States)

   Affiliation as printed

   Janssen Research and Development, Raritan, New Jersey , USA

6. Todd A. Davies

   Janssen Research & Development (United States)

   Affiliation as printed

   Janssen Research and Development, Raritan, New Jersey , USA

7. Germie van den Dobbelsteen Aachen Bacterial Vaccines Discovery and Early Development

   Janssen (Netherlands)

   Affiliation as printed

   Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V. , Leiden , The Netherlands

8. JAN T. POOLMAN Aachen Bacterial Vaccines Discovery and Early Development

   Janssen (Netherlands)

   Affiliation as printed

   Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V. , Leiden , The Netherlands

9. Darren Abbanat

   Janssen Research & Development (United States)

   Affiliation as printed

   Janssen Research and Development, Raritan, New Jersey , USA

10. Wouter Haazen

    Janssen (Belgium)

    Affiliation as printed

    Infectious Diseases and Vaccines, Janssen Research and Development, Janssen Pharmaceutica , Beerse , Belgium