Construction and characterization of genetically-marked bivalent anti-Shigella dysenteriae1 and anti-Shigella flexneriY live vaccine candidates

Development and Preclinical Evaluation of a Trivalent, Formalin-Inactivated Shigella Whole-Cell Vaccine

“…A significant hurdle with Shigella vaccines that rely on LPS antigens for immunogenicity and protection is the diversity of O antigens expressed by differing serotypes. Previous studies have shown that the addition of two LPS serotypes in a bivalent formulation did not result in competition or interference (36,40,43). In the studies presented here, immunization with a combination of three SWC vaccines resulted in lower LPS-specific immunogenicity than the immune responses induced with the monovalent counterpart that resulted in reduced efficacy.…”

Serotype conversion of a Shigella flexneri candidate vaccine strain via a novel site-specific chromosome-integration system

“…Another major advantage of the bacteriophage-based integration system is that it normally does not disrupt functionally important genes of the host strain. Unlike transposon-based insertion vectors which are randomly inserted into the host chromosome [14,15,25], phage-based integration system usually chooses a unique site in the chromosome (bacterial attachment site, attB) as the preferred insertion site [26]. For example, the prophage of bacteriophage V lies in intergenic DNA [27].…”

“…This requirement can be circumvented by introducing a non-antibiotic selection marker for screening the chromosomally integrated clones. For example, an arsenite-resistance marker has been used for the construction of transposon-based integration vectors [14,15], and a mercury-resistance marker has also been used for the construction of a homologous replacement-based suicide vector [28]. The bacteriophage-based integration systems of other bacteria, especially those of E. coli, Salmonella enterica and some Gram-positive bacteria, should also be explored in order to develop integration vectors that are speci¢c to those bacteria.…”

“…SFL124 has been proven a safe and immunogenic vaccine candidate with negligible side effects in Swedish and Vietnamese volunteers [11,12]. Although many strategies have been explored in engineering the bacterial serotypes, including introduction of plasmids [13] and random insertions of transposon-based insertion vectors [14,15], using a bacteriophage site-speci¢c integration system to modify the bacterial O-antigen serotype has not been reported. We believe that this strategy may be an e¡ective way to introduce a single copy of foreign genes into the bacterial chromosome at a speci¢c site without interrupting any important host genes.…”

Strategies for the development of vaccines conferring broad-spectrum protection

“…serotypespecific, but multivalent protective immunity has been exploited by other approaches as well. Klee et al (1997) vaccinated with a single attenuated Shigella strain expressing heterologous LPS molecules. Alternatively, detoxified and protein-conjugated LPS molecules (Cohen et al, 1997;Taylor et al, 1993) or even synthetic oligosaccharides mimicking O-antigens (Phalipon et al, 2006) could be used to elicit immunity against shigellosis.…”