System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Clinical Trial, Phase I Research Support, Non-U.S. Gov't Ppublish 1 citation

PubMed: 39397784 DOI: 10.1080/21645515.2024.2410574

A novel orf virus vector-based COVID-19 booster vaccine shows cross-neutralizing activity in the absence of anti-vector neutralizing immunity.

Hum Vaccin Immunother 20(1):2410574

Authors: Ute Klinkardt, Mirjam Schunk, John Ervin, Christoph Schindler, Danny Sugimoto, Bruce Rankin, Ralf Amann, Martina Monti, Anna Kutschenko, Carsten Schumacher, Kristina Huber, Andreas Zeder, Nelli Heikkila, Arnaud M Didierlaurent, Sylvia E Schwarz, Madiha Derouazi

Affiliations

  • Speransa Therapeutics, TowerOne (Spaces), Frankfurt am Main, Germany.
  • Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital, Munich, Germany.
  • AMR - Center for Pharmaceutical Research, Kansas City, MO, USA.
  • Medizinische Hochschule Hannover (MHH), Center for Clinical Trials (ZKS) - Early Clinical Trial Unit (ECTU), Hanover, Germany.
  • Cedar Crosse Research Cente, Chicago, IL, USA.
  • Accel Research Sites (ARS) - Corporate Office, DeLand, FL, USA.
  • Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
  • VisMederi Srl, Siena, Italy.
  • Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Abstract

Next-generation COVID-19 vaccines are being developed to expand the breadth of coverage against existing and future variants and to extend the duration of protection. Prime-2-CoV_Beta is an orf virus (ORFV) based multi-antigen COVID-19 vaccine that co-expresses Spike (S) and Nucleocapsid (N) antigens. The safety and immunogenicity of Prime-2-CoV_Beta is investigated in a phase 1 first-in-human (FIH) dose-finding trial (ORFEUS study, ClinicalTrials.gov: NCT05367843). Participants of two age groups (18-55 and 65-85 years) who previously completed at least two doses of mRNA vaccines were enrolled and sequentially assigned to different dose groups to receive one intramuscular dose of 3 × 10, 3 × 10, 1.5 × 10, or 3 × 10 plaque-forming units (PFU) of Prime-2-CoV_Beta on day 1 and a second dose on day 29. Here, we report safety and immunogenicity data collected up to 6 months after the first study vaccination. Prime-2-CoV_Beta is safe and well tolerated and elicits immune responses at higher dose levels in participants aged 18-55. A single dose of 3 × 10 PFU boosted binding and cross-neutralizing antibody responses that are maintained through 6 months after the first booster vaccination. Polyfunctional S-specific CD4+ and CD8+ T cell responses are observed after vaccination. No pre-existing or vaccine-induced neutralizing anti-vector antibodies are detected. Our findings highlight the potential of the ORFV vector as a safe platform for future vaccine design, which provides the ability to deliver multiple antigens and allows for repeat immunization.

MeSH

Ecthyma, Contagious, Safety, Absenteeism, Vaccines, Covid-19 Vaccines, Orf Virus, Multiple Chronic Conditions, Vaccination, Covid-19, Viruses, Immunity

Cited by