Researchers Eye Certain Strains for Developing Possible Shigella flexneri Vaccine

Two new vaccine strains may be viable candidates for the creation of a multivalent vaccine that could protect against a broad spectrum of Shigella flexneri infections, according to data presented at ASM Microbe 2016.

Vaccine development for Shigella flexneri has been limited, because the vaccine requires serotype-specific protection. Therefore, researchers from the University of Maryland in Baltimore assessed 2 vaccine candidates, comparing them to the attenuated Shigella flexneri 2a vaccine CVD 1208S. These new strains, CVD 1213 and CVD 1215, represent 2 prominent Shigella flexneri serotypes that could offer broad spectrum immunity from shigellosis when combined with CVD 1208S.

The vaccine strains were attenuated with a deletion in the guaBA operon encoding critical enzymes of the de novo guanine nucleotide biosynthesis pathway. The researchers measured host responses to the vaccines using macrophage cytotoxicity assays, gentamicin protection assays to determine invasion and replication rates, and enzyme-linked immunosorbent assays to measure the rate of cytokine secretion from infected cells.

The researchers also performed studies in guinea pigs to assess Shigella LPS-specific antibody responses and protection against wild type challenge following immunization. They assessed each vaccine individually, and in combination as a trivalent mixed vaccine.

The results showed that epithelial cell invasion by the vaccine strains was not decreased when compared with wild type, although the attenuated vaccines were unable to replicate intracellularly. The vaccine candidates revealed varied cytotoxic effects in human macrophages, but were still comparable to the parental wild type strains. In addition, cytokine secretion from macrophages and epithelial cells infected with the vaccine strains was consistent with secretion from wild type cells, and was significantly higher than secretion in uninfected cells.

In the guinea pig immunization study, researchers observed various Shigella serotype specific IgA and IgG antibodies (100% seroconversion) following immunization of each individual vaccine strain, and the 3-strain combination. The guinea pig Sereny test also demonstrated protection against wild type, Shigella flexneri serotypes 2 a, 3a, and 6 following a combination immunization including CVD 1208S, CVD 1213, and CVD 1215.

Shigella flexneri is an enteroinvasive bacterium that is currently one of the leading causes of diarrheal disease in children under 5 years of age in developing countries. 

Reference

DeLaine B, Grassel C, Wu T, Barry EM. Session 093. Characterization of new live, attenuated Shigella flexneri  vaccine candidates. Presented at the American Society for Microbiology Microbe 2016; June 16-20, 2016; Boston, MA