Optimization ofSalmonella entericaSerovar Typhi ΔaroCΔssaVDerivatives as Vehicles for Delivering Heterologous Antigens by Chromosomal Integration and In Vivo Inducible Promoters

Abstract

Novel candidate live oral vaccines based on aSalmonella entericaserovar Typhi ZH9 (Ty2 ΔaroCΔssaV) derivative that directed the expression of either the B subunit ofEscherichia coliheat-labile toxin or hepatitis B virus core antigen from the bacterial chromosome using the in vivo induciblessaGpromoter were constructed. The levels of attenuation of the twoS. entericaserovar Typhi ZH9 derivatives were similar to that of the parent as assessed by measuring the replication of bacteria within human macrophage-like U937 cells. The expression of heterologous antigen in the respectiveS. entericaserovar Typhi ZH9 derivatives was up-regulated significantly within U937 cells compared to similarS. entericaserovar Typhi ZH9 derivative bacteria grown in modified Luria-Bertani broth supplemented with aromatic amino acids. Immunization of mice with theseS. entericaserovar Typhi ZH9 derivatives stimulated potent antigen-specific serum immunoglobulin G responses to the heterologous antigens.