Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the Live Salmonella Oral Vaccine Vector Ty21a.

We have been exploring the use of the live attenuated serovar Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression and delivery of multiple foreign antigens, including O-antigens. In this study, we separately cloned genes necessary for the biosynthesis of the serotype 2a and 3a O-antigens, which have been shown to provide broad cross-protection to multiple disease-predominant serotypes. The cloned 2a operon, along with and , contained on the SfII bacteriophage, was sufficient in Ty21a to express the heterologous 2a O-antigen containing the 3,4 antigenic determinants.

Stable expression of Shigella dysenteriae serotype 1 O-antigen genes integrated into the chromosome of live Salmonella oral vaccine vector Ty21a.

Typhoid fever and shigellosis cause high morbidity and mortality worldwide, yet no anti-Shigella vaccine is currently available. However, to protect against typhoid fever, an approved vaccine, based on the attenuated Salmonella enterica serovar Typhi strain Ty21a is available. We have investigated Ty21a as a live oral vaccine vector for expression of heterologous foreign antigens to protect against other diseases (e.

Stable expression of Shigella sonnei form I O-polysaccharide genes recombineered into the chromosome of live Salmonella oral vaccine vector Ty21a.

Live, attenuated Salmonella enterica serovar Typhi strain Ty21a, a licensed oral typhoid fever vaccine, has also been employed for use as a vector to deliver protective antigens of Shigella and other pathogens. Importantly, lipopolysaccharide (LPS) alone has been shown to be a potent antigen for specific protection against shigellosis. We reported previously the plasmid cloning of heterologous LPS biosynthetic genes and the expression in Ty21a of either S.

Lot consistency as an equivalence problem.

One requirement for licensure of a vaccine in the United States is demonstration by the manufacturer of consistently produced lots of vaccine. Demonstration of consistency of manufacturing can be viewed as a multigroup equivalence problem. The standard statistical procedures for evaluating equivalence assume normally distributed data and define equivalence margins with respect to group means.