Protective immunity by oral immunization with heat‐killed Shigella strains in a guinea pig colitis model

Abstract

The protective efficacy of and immune response to heat-killed cells of monovalent and hexavalent mixtures of six serogroups/serotypes of Shigella strains (Shigella dysenteriae 1, Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, Shigella boydii 4, and Shigella sonnei) were examined in a guinea pig colitis model. A monovalent or hexavalent mixture containing 1 Â 10 7 of each serogroup/serotype of heatkilled Shigella cells was administered orally on Days 0, 7, 14 and 21. On Day 28, the immunized animals were challenged rectally with 1 Â 10 9 live virulent cells of each of the six Shigella serogroups/serotypes. In all immunized groups, significant levels of protection were observed after these challenges. The serum titers of IgG and IgA against the lipopolysaccharide of each of the six Shigella serogroups/ serotypes increased exponential during the course of immunization. High IgA titers against the lipopolysaccharide of each of the six Shigella serogroups/serotypes were also observed in intestinal lavage fluid from all immunized animals. These data indicate that a hexavalent mixture of heat-killed cells of the six Shigella serogroups/serotypes studied would be a possible broad-spectrum candidate vaccine against shigellosis.

Passive immunity with multi‐serotype heat‐killed Shigellae in neonatal mice

“…The current study confirmed the efficacy of the heat‐killed hexavalent Shigella vaccine , by investigating protective immunity in an infant mouse model wherein the offspring of immunized dams were challenged by wild strains of Shigellae. The level of protection was measured as the degree of colonization of the challenged bacteria in the bowel .…”

“…To develop a vaccine that confers broad‐spectrum coverage requires the inclusion of all epidemic and endemic Shigella serotypes . Recently, we reported that an oral vaccine candidate of heat‐killed Shigella strains ( S. dysenteriae 1, S. flexneri 2a, S. flexneri 3a, S. flexneri 6, S. boydii 4, and S. sonnei ) achieved significant levels of protection against shigellosis in a guinea pig colitis model . Similarly, Kaminski et al reported the successful development of a trivalent, formalin‐inactivated Shigella whole‐cell vaccine.…”

International Collaborative Research on Infectious Diseases by Japanese Universities and Institutes in Asia and Africa, with a Special Emphasis on J-GRID

“…The serum titers of IgG and IgA against lipopolysaccharide of each of the six Shigella serogroups/serotypes increased. These data indicate that a hexavalent mixture of heat-killed cells of the six Shigella serogroups/serotypes tested would be a possible broad-spectrum candidate vaccine against shigellosis Barman et al, 2013 . In an oral immunization trial on two-month-old guinea pigs, the heat-killed cell suspension of monovalent or Roszak and Colwell, 1987 . Existence of viable but nonculturable VBNC V. cholerae is the one reasonable explanation for the difficulty of isolation of viable cells of the vibrio from the environmental water samples.…”

Heat killed multi-serotype Shigella immunogens induced humoral immunity and protection against heterologous challenge in rabbit model

“…With these points in mind, we have formulated a heat-killed hexavalent prototype vaccine from a combination of six Shigella strains: S. dysenteriae 1 (NT4907 stx), S. flexneri 2a (B294), S. flexneri 3a (C519), S. flexneri 6 (C347), S. sonnei (IDH00968) and S. boydii 4 (BCH612). Our recent laboratory study showed that these newly formulated hexavalent immunogens successfully induce a homologous protective response in guinea-pig rectocolitis model (Barman et al, 2013).…”