Therapeutic vaccination with Salmonella-delivered codon-optimized outer inflammatory protein DNA vaccine enhances protection in Helicobacter pylori infected mice

Abstract

Vaccination had demonstrated as an alternative way to combat Helicobacter pylori challenge. In the present study, codon-optimized outer inflammatory protein gene (oipA) for Mus species codon usage, the inclusion of optimal Kozak sequence, and modified of GC content was applied to construct a novel DNA construct. The Salmonella-delivered wild type oipA construct (SL7207/poipA) and the Salmonella-delivered codon-optimized oipA construct (SL7207/poipA-opt) were prepared and their therapeutic efficacy was evaluated in H. pylori-infected mice. The codon-optimized oipA construct (poipA-opt) expressed almost six-fold higher protein than that of wild type construct (poipA) as normalized to the β-actin expression in AGS cells. Oral therapeutic immunization with SL7207/poipA-opt significantly eliminated H. pylori colonization in the stomach; and protection was related to a robust Th1/Th2 immune response. Therefore, our results suggested that fine therapeutic efficacy was related to sufficient expression of the antigen. It is supposed that codon-optimized oipA gene improves protein expression and consequently enhances the immunogenicity of DNA vaccine, which resulted in a significant reduction of bacterial loads in H. pylori infected mice. The Salmonella-delivered codon-optimized DNA construct could be a candidate vaccine against H. pylori for the clinical application.