Oral delivery of SARS-CoV-2 DNA vaccines using attenuatedSalmonella typhimuriumas a carrier in rat

Abstract

The 2019 novel coronavirus disease (COVID-19) is the disease that has been identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the prophylactic treatment of SARS-CoV-2 is still under investigation. The effective delivery of eukaryotic expression plasmids to the immune system’s inductive cells constitutes an essential requirement for the generation of effective DNA vaccines. Here, we have explored the use of Salmonella typhimurium as vehicles to deliver expression plasmids orally. Attenuated Salmonella phoP harboring eukaryotic expression plasmids that encoded spike protein of SARS-CoV-2 was administered orally to Wistar rats. Rats were immunized orally with Salmonella that carried a eukaryotic expression plasmid once a week for three consecutive weeks. The efficiency of the vaccination procedure was due to the transfer of the expression plasmid from the bacterial carrier to the mammalian host. Evidence for such an event could be obtained in vivo and in vitro. Our results showed that all immunized animals generated humoral immunity against the SARS-CoV-2 spike protein, indicating that a Salmonella-based vaccine carrying the Spike gene can elicit SARS-CoV-2-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV-2 infection.

COVID-19 vaccine development based on recombinant viral and bacterial vector systems: combinatorial effect of adaptive and trained immunity

“…Deletion of the virulence transcriptional regulatory protein phoP enabled the generation of an attenuated S. typhimurium vaccine platform (Groisman et al, 1989;Methner et al, 2004). In a recent study, oral administration of recombinant attenuated S. typhimurium, which contains the fulllength spike gene of SARS-CoV-2, exerted a protective effect against SARS-CoV-2 infection, mainly by inducing SARS-CoV-2-specific humoral immunity, in a rat model, suggesting the feasibility of a COVID-19 oral vaccine (Zhu et al, 2020b) (Table 5).…”