Synthetic O-Polysaccharide Backbone Units for a Single Antigen Vaccine Against Two Major Non-Typhoidal Salmonella...

Salmonella infections can cause life-threatening systemic diseases in many regions of the world. With the prevalence of antimicrobial-resistant Salmonella, vaccines are urgently needed to prevent and reduce infections. There are no vaccines available against any non-typhoidal Salmonella (NTS) serovars, including two of the most common ones, that are, Salmonella Typhimurium and Salmonella Enteritidis. While traditional Salmonella vaccine approaches require a construct against each serotype, a new strategy has been developed in this work targeting the shared O-polysaccharide backbone as a potential common vaccine antigen. Tri-, hexa-, and nona-saccharides corresponding to one to three repeating units of the O-polysaccharide backbone were synthesized stereoselectively via a modular approach. These oligosaccharides were conjugated to the bacteriophage Qβ carrier, which elicited strong IgG responses against the synthetic carbohydrate antigens upon immunization of both mice and rabbits. The trisaccharide antigen was sufficient to induce protective antibodies. The post-immune sera from Qβ-trisaccharide immunized rabbits recognized the native O-polysaccharides from both S. Typhimurium and S. Enteritidis, and significantly protected mice against lethal challenges by these Salmonella serotypes. The ability of a single glycan antigen to protect against infections by two different NTS serovars is a significant step forward for broad-spectrum anti-Salmonella vaccine design.