A type IVB pili operon promoter controlling nucleocapsid gene expression of SARS-CoV in Salmonella elicits full immune response by intranasal vaccination

Abstract

Attenuated Salmonella enterica serovar typhi have been implicated attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar typhi strain stably expressing conserved nucleocapsid (N) protein of SARS-CoV by integrating the N gene into the pilV gene which was under the control of the type IVB pili operon promoter in S. enterica serovar typhi. BALB/c mice were immunized with this recombinant strain through different immune routes, viz intranasaly (i. n.), orogastricaly (o. g.), intraperitonealy (i. p.), and intravenously (i. v.). Results showed that i. n. route caused the highest production of specific IgG, IgG2a, and SIgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T lymphocytes (CTL) activities, and increased IFN-gamma producing T cells compared with the parental strain. Our work provide insights that the type IVB pili operon promoter controlling SARS-CoV N gene expression in Salmonella might be an attractive live vector vaccine against the infection of SRAS-CoV for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pili operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.