Safety and Immunogenicity of Homologous Recombinant Adenovirus Type5-Vectored COVID-19 Vaccine Booster Dose in Healthy Adults Aged 18-60 Years: a Single-Center, Open-Label Trial.

Abstract

The waning antibody levels several months after prime vaccination and the persistent epidemics of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) around the world have generated great interest in the evaluation of a booster dose. We aimed to assess the safety and immunogenicity of a homologous booster dose of the recombinant adenovirus type5-vectored coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV). In this trial, we recruited healthy adults aged 18-60years who had received one dose of Ad5-nCoV vaccine (low, middle, or high dose) in the previous phase1 trial approximately 6months earlier, and then all participants received a booster dose of 5 × 1010 viral particles (low dose) intramuscularly. The primary outcome was the incidence of adverse reactions within 14days after booster vaccination. The specific binding antibodies were measured by enzyme-linked immunosorbent assay and the neutralizing antibody responses were assessed with live SARS-CoV-2 and pseudovirus neutralization assay. The cellular immune responses were analyzed by enzyme-linked immunospot assay and intracellular cytokine staining. From September26 to 28, 2020, 108 volunteers were recruited and 89 eligible participants (52% male) were enrolled and received a booster dose of Ad5-nCoV vaccine: 28 (31%) had received a low prime dose, 30 (34%) a middle prime dose, and 31 (35%) a high prime dose in the previous phase1 trial. All participants were included in the safety analysis and immunogenicity was assessed in 88 (99%) participants. Twenty-three (82%) participants in the low prime dose group, 23 (77%) participants in the middle prime dose group, and 26 (84%) participants in the high prime dose group reported at least one adverse reaction within the first 14days post booster. Pain at the injection site and fatigue were the most common adverse reactions. Most adverse reactions were mild or moderate in all groups and no vaccine-related severe adverse event was noted within 12months after booster vaccination. Neutralizing antibodies increased moderately at day14 and peaked at 28days post booster. Tcell responses were also boosted at 14days after vaccination. A homologous booster of Ad5-nCoV vaccine is well tolerated and immunogenic in healthy adults aged 18-60years who had received a priming dose of Ad5-nCoV 6months previously. The neutralizing antibodies against SARS-CoV-2 peaked at day28 and specific Tcell responses were noted at day14 after booster. Ad5-nCoV vaccine can be considered as a homologous booster 6months after a priming dose. ClinicalTrials.gov, NCT04568811.