The efficacy and immunogenicity of a live transconjugant hybrid strain of Shigella dysenteriae type 1 in two animal models

Abstract

In our earlier studies, we constructed a hybrid strain of Shigella dysenteriae type 1 by introducing a plasmid vector pPR 1347. After introduction of a lipopolysaccharide (LPS) biosynthesis gene, virulent Shigella dysenteriae type 1 strain became avirulent. In our present study, we have evaluated the immune response and protective efficacy of avirulent live transconjugant Shigella hybrid (LTSH) strain against wild type Shigella dysenteriae type 1, after four doses of oral (rabbit) and intranasal (mouse) immunizations. Serum IgG titers showed exponential increase during immunization and peaking on the 28th day and remained at that level till the 35th day in both the rabbit and the mouse models. When tested, serum IgG titers persisted for 63 days in mice and relatively high for 150 days in case of rabbits. Protection studies showed 100% protection against the challenge with wild type Shigella dysenteriae type 1 strain in rabbits and 80% protection in mice. Our results suggested that the LTSH strain could be a useful vaccine candidate strain in the future.

Live non‐invasive Shigella dysenteriae 1 strain induces homologous protective immunity in a guinea pig colitis model

“…It was shown that IpaH protein was not secreted, although a possible genetic or molecular mechanism was not elucidated (12). LTSH showed 100% protection against the challenge with wild type S. dysenteriae 1 strain in rabbits and 80% protection in mice (13).…”

“…The constructed transconjugant became non‐invasive and stopped IpaH secretion. The oral immunization of mice and rabbits resulted in the production of specific antibodies for homologous LPS antigens and showed an effective protection against virulent wild S. dysenteriae 1 strain (13). In this study, we investigated the immunogenicity and protective efficacy of a live non‐invasive Shigella strain constructed from a Shiga toxin gene deleted S. dysenteriae 1 in a recently developed guinea pig colitis model (14) and discussed its usefulness to induce protective immunity against S. dysenteriae 1 infection.…”

Immunization of Mice with a Live Transconjugant Shigella Hybrid Strain Induced Th1 and Th17 Cell‐Mediated Immune Responses and Confirmed Passive Protection Against Heterologous Shigellae

“…Wild‐type S. dysenteriae 1 strain was isolated from an epidemic in West Bengal (India) . A cosmid vector carrying pPR1347 containing both the rfb gene cluster and the rfc gene from Salmonella Typhimurium was inserted into the Δ stx derivative , and this strain was used for immunization as the hybrid strain (transconjugant).…”

“…The oral immunization of mice and rabbits with this strain resulted in the production of specific antibodies against homologous LPS antigens and showed effective protection against virulent wild S . dysenteriae 1 strain . In another study, a non‐invasive live transconjugant Shigella hybrid strain was constructed by introducing a plasmid vector pPR1347 that carried a lipopolysaccharide biosynthesis gene ( rfb and rfc ) of Salmonella Typhimurium (LTSHΔ stx ) into a mutant deleted of the Shiga toxin gene .…”