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.
Highlights
The rapid and global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), calls for urgent development of safe, effective, and equitably accessible vaccines
The coding sequences of S or receptor-binding domain (RBD) were inserted into the E1 region of the AdC68 vector under the control of the CMV promoter and terminated with a bovine growth hormone (BGH) polyadenylation signal sequence
Surface expression of S and intracellular expression of the RBD were further confirmed by staining with the RBD-specific mAbs P2C-1F11 and P2B-2F, initially isolated from SARSCoV-2 infected individuals (Figure 1C)
Summary
The rapid and global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), calls for urgent development of safe, effective, and equitably accessible vaccines. The adenovirus-based vaccines, developed by CanSino (Ad5) [6], Gamaleya (Ad5 and Ad26) [7], AstraZeneca/Oxford University (ChAdOX1) [8], and Johnson & Johnson (Ad26) [9], have incorporated novel features for antigen and vector optimization and have recently been approved for emergency use by several regulatory agencies. Those based on human adenovirus serotype 5 (Ad5) may compromise their efficacy due to preexisting immunity to the vector. Additional vaccine platforms, based on DNA, recombinant proteins, or novel viral vectors, are being developed [15,16,17]
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