Salmonella-mediated oral delivery of multiple-target vaccine constructs with conserved and variable regions of SARS-CoV-2 protect against the Delta and Omicron variants in hamster

Since the emergence of the pandemic COVID19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of vaccines has been the prime strategy to control the disease transmission. Most of the developed vaccines target the spike protein, however, the emerging variants have alterations, particularly at the same region which may pose resistance to neutralizing antibodies. In this study, we explored the variable and conserved regions of SARS-CoV-2 as a potential inclusion in a multiple-target vaccine with the exploitation of Salmonella-based vector for oral mRNA vaccine against Delta and Omicron variants. Increased IgG and IgA levels imply the induction of humoral response and the CD4⁺, CD8⁺ and IFN-γ⁺ sub-population level exhibits cell-mediated immune responses. The degree of CD44⁺ cells indicates the induction of memory cells corresponding to long-term immune responses. Furthermore, we assessed the protective efficacy of the vaccines against the Delta and Omicron variants in the hamster model. The vaccine constructs induced neutralizing antibodies and protected the viral-challenged hamsters with significant decrease in lung viral load and reduced histopathological lesions. These results reinforce the use of the conserved and variable regions as potential antigen targets of SARS-CoV-2 as well as the exploitation of bacteria-mediated delivery for oral mRNA vaccine development.