Abstract: Disclosed herein are transgenic Salmonella typhi Ty21a comprising a chromosome with one or more heterologous nucleic acid regions, wherein the heterologous nucleic acid regions encode one or more viral antigens and are integrated into the Salmonella typhi Ty21a chromosome, and wherein the transgenic Salmonella typhi Ty21a stably expresses the one or more viral antigens. Also disclosed herein are compositions and vaccines comprising the transgenic Salmonella typhi Ty21a. Also disclosed herein are methods of eliciting an immune response in a subject against a SARS-CoV-2 viral antigen and/or a Salmonella typhi antigen comprising administering one or more doses of the composition or the vaccine to the subject. Also disclosed herein are methods of treating, preventing or reducing the incidence of COVID-19 and/or typhoid fever in a subject comprising administering one or more doses of the composition or the vaccine to the subject.