An open-label study on the safety and immunogenicity of a PD-1-enhanced DNA vaccine used as a T cell booster for COVID-19

Abstract

Background: Inducing T cell responses by vaccines among elderly has been a long-standing challenge. There is a need for effective COVID-19 vaccines to boost waning immunity against emerging SARS-CoV-2 variants, especially for the elderly. This study investigated the safety and immunogenicity of a PD-1-enhanced COVID-19 DNA vaccine (ICCOV™), as a booster vaccine in healthy adults (aged 18–59 years) and elderly (aged 60–75 years). Methods: This open-label, non-randomised Phase 2 study enrolled healthy participants aged 18–75 years who had previously been vaccinated with Sinovac CoronaVac, Pfizer-bioNTech Comirnaty vaccines, or both. Participants were stratified into four cohorts according to age, primary vaccination, and COVID-19 infection history, namely Adult-CoronaVac, Adult-Comirnaty, Adult-Mixed, and Elderly-Mixed cohorts. Participants were administered with a single dose of 2 mg ICCOV intramuscularly followed by electroporation using the proprietary TERESA-EPT-I device. Participants were followed up for 60 days. The primary endpoint was T cell immunogenicity within 28 days post-ICCOV vaccination. The secondary endpoints were safety, T cell and antibody responses within 60 days post-vaccination (ClinicalTrials.gov NCT05904054). Findings: The study was conducted at Gleneagles Hospital Hong Kong between 30 June and 30 November 2023. In total, 31 participants were enrolled across the Adult-Comirnaty (n = 4), Adult-Mixed (n = 15), and Elderly-Mixed (n = 12) cohorts. All enrolled participants completed the study and were included in safety and immunogenicity analyses. Among these participants, 2 from the Adult-Comirnaty cohort, 9 from the Adult-Mixed cohort, and 4 from the Elderly-Mixed cohort reported a total of 31 adverse events, all in grade 1–2. Pain at the administration site was the most frequently reported (38·7%). The proportion of participants demonstrating an increase of SARS-CoV-2-specific ELISpot T cell responses within 28 days post ICCOV vaccination was 100% (4/4), 80% (12/15), and 75% (9/12) in Adult-Comirnaty, Adult-Mixed, and Elderly-Mixed cohorts, respectively. Single ICCOV vaccination elicited SARS-CoV-2-specific, polyfunctional CD8+ and CD4+ T cells against both ancestral and Omicron strains in all cohorts. The magnitude of responses was not inferior in the elderly, compared to adults. No elevation of antibody responses was detected. Interpretation: Single PD-1-enhanced ICCOV booster DNA vaccination did not show major safety concerns. The ICCOV booster elicited cross-reactive T cell responses to multiple SARS-CoV-2 strains, including in the elderly. This report demonstrates the T-cell boosting immunogenicity of ICCOV in the susceptible elderly population. Funding: Clinical Translational Catalyst, Hong Kong Science & Technology Parks Corporation.