Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection

Abstract

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies

“…Syrian hamster model was used to evaluate the protective efficacy of several inactivated vaccines [ 45–46 ], including ones certified for clinical use [ 31 ]. The main evaluated parameters were weight, virus and/or viral RNA presence in nasal swabs, lungs and other organs on different terms post infection.…”

Non-clinical immunogenicity, biodistribution and toxicology evaluation of a chimpanzee adenovirus-based COVID-19 vaccine in rat and rhesus macaque

“…927, 2005; EMA CHMP/VWP/141697/2009). The rat and rhesus macaque were standard test species for use in toxicity studies and previous report has proved that AdC68-19S can induce humoral and cellular immune responses in BalB/c mice, Golden Syrian Hamster and rhesus macaque (Li et al 2021 ). The rats and rhesus macaques were injected intramuscularly with AdC68-19S up to 2 × 10 11 vp/dose or 4 × 10 11 vp/dose on two or three occasions with a 14-day interval period respectively.…”

“…It can recognize receptor and mediate virus entry into host cells and serves as the major target for COVID-19 vaccine (Wang et al 2020 ). AdC68-19S has been proved to induce sustained and protective immunity against SARS-CoV-2 infection in BalB/c mice, Golden Syrian Hamster and rhesus macaque (Li et al 2021 ). Here, we evaluated the immunogenicity, biodistribution and in vivo toxicological profiles of AdC68-19S in rat and rhesus macaque under good laboratory practice (GLP) conditions.…”

A recombinant SARS-CoV-2 RBD antigen expressed in insect cells elicits immunogenicity and confirms safety in animal models

“…However, there are several vaccine candidates based on the single RBD antigen, ongoing pre-clinical and clinical phase [20]. Although, in some reports the complete spike has shown greater immunogenicity [21], the single RBD remains as a strong vaccine candidate because it comprises the most important epitopes to which neutralizing antibodies should target. In addition, it generates antibodies with enhanced neutralizing activity [22][23][24].…”