Abstract
Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 has rapidly expanded into a serious global pandemic. Due to the high morbidity and mortality of COVID-19, there is an urgent need to develop safe and effective vaccines. AdC68-19S is an investigational chimpanzee adenovirus serotype 68 (AdC68) vector-based vaccine which encodes the full-length spike protein of SARS-CoV-2. Here, we evaluated the immunogenicity, biodistribution and safety profiles of the candidate vaccine AdC68-19S in Sprague Dawley (SD) rat and rhesus macaque under GLP conditions. To characterize the biodistribution profile of AdC68-19S, SD rats were given a single intramuscular injection of AdC68-19S 2 × 10 11 VP/dose. Designated organs were collected on day 1, day 2, day 4, day 8 and day 15. Genomic DNA was extracted from all samples and was further quantified by real-time quantitative polymerase chain reaction (qPCR). To characterize the toxicology and immunogenicity profiles of AdC68-19S, the rats and rhesus macaques were injected intramuscularly with AdC68-19S up to 2 × 10 11 vp/dose or 4 × 10 11 vp/dose (2 and fourfold the proposed clinical dose of 1 × 10 11 vp/dose) on two or three occasions with a 14-day interval period, respectively. In addition to the conventional toxicological evaluation indexes, the antigen-specific cellular and humoral responses were evaluated. We proved that multiple intramuscular injections could elicit effective and long-lasting neutralizing antibody responses and Th1 T cell responses. AdC68-19S was mainly distributed in injection sites and no AdC68-19S related toxicological reaction was observed. In conclusion, these results have shown that AdC68-19S could induce an effective immune response with a good safety profile, and is a promising candidate vaccine against COVID-19.
Keywords: Biodistribution; COVID-19 vaccine; Chimpanzee adenovirus vector; Immunogenicity; Toxicology.
【저자키워드】 COVID-19 vaccine, immunogenicity, toxicology., Chimpanzee adenovirus vector, biodistribution, 【초록키워드】 COVID-19, SARS-CoV-2, Vaccine, coronavirus, immune response, Th1, Adenovirus, global pandemic, DNA, Humoral response, qPCR, T cell responses, toxicology, morbidity and mortality, Quantitative, safety profile, Neutralizing antibody response, rhesus macaque, cellular, dose, Safe, Intramuscular injection, acute respiratory syndrome, serotype, profile, Effective vaccines, injection, candidate vaccine, organ, full-length spike protein, rhesus, ENCODE, effective, polymerase chain, shown, collected, develop, caused, addition, evaluated, injected, were given, long-lasting, elicit, induce, conditions, quantified, Chimpanzee, intramuscularly, 【제목키워드】 rhesus, adenovirus-based,