Construction of a multivalent vaccine strain ofShigella flexneriand evaluation of serotype-specific immunity

Abstract

Shigella flexneri causes more fatalities by shigellosis than any other Shigella species. There are 13 different serotypes of S. flexneri and their distribution varies between endemic geographical regions. The immune response against S. flexneri is serotype-specific, so current immunization strategies have required the administration of multiple vaccine strains to provide protection against multiple serotypes. In this study, we report the construction of a multivalent S. flexneri vaccine strain, SFL1425, expressing the O-antigen structure specific for serotypes 2a and 5a. This combination of type antigens has not previously been reported for S. flexneri. The multivalent vaccine strain, SFL1425 was able to induce a specific immune response against both serotypes 2a and 5a in a mouse pulmonary model.

Changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010

“…The World Health Organization has made the development of a safe and effective vaccine against S. flexneri [1,[6][7][8], but the vaccine effectiveness depends on the distribution patterns of local species and serotypes, because only type-specific immunity has been demonstrated in humans [9][10][11][12] and moreover cross-serotype protection is controversial [11,13].…”

Emergence of a New Multidrug-Resistant Serotype X Variant in an Epidemic Clone of Shigella flexneri

“…Our results also highlight that for a vaccine to be successful in controlling S. flexneri infections, the vaccine must cover multiple serotypes. A number of strategies have been tried to develop such vaccines (14,22). Noriega et al (22) used two S. flexneri serotypes (2a and 3a) to cover all "type" and "group" antigenic factors for S. flexneri serotypes 1 to 5, but the vaccine offered protection against only four of the six S. flexneri serotypes tested (22).…”

Shigellose ou dysenterie bacillaire

“…Il pourrait être monovalent avec des souches comme SC 602 de S. flexneri 2a (délétion des gènes ics A et iuc)[82], SC 599 de S. dysenteriae (délétion des gènes ics A, ent, fep), WRSS1 de S. sonnei (délétion du gène ics A)[83], ou encore la gamme CVD (1203, 1204, 1207)[80]. Il pourrait être multivalent comprenant une association de souches anti-flexneri (et ses sérotypes), anti-sonnei, et/ou anti-dysenteriae[84,85]. Une autre approche expérimente une souche porteuse pour véhicu-ler l'antigène somatique lipopolysaccharidique de Shigella, telle la souche vaccinale atténuée Ty21a de Salmonella typhi déjà bien étudiée et administrable per os[86].…”