Development of an auxotrophic oral live Shigella flexneri vaccine

Lindberg, Annelie; Kärnell, Anders; Stocker, B. A. D.; Katakura, S.; Sweiha, Hanaa; Reinholt, Finn P.

doi:10.1016/s0264-410x(88)80018-5

Cited by 79 publications

(40 citation statements)

References 20 publications

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“…This integration is essential for design and improvement of live attenuated vaccine candidates. However, in vivo studies are complicated by the relatively innate resistance of most animals to oral infection by S. flexneri (24), which impairs the coordinated analysis of invasion, inflammation, and immunity. In studies aimed at exploring protection against shigellosis, Shigella vaccines are often evaluated using methods of inoculation that differ from the normal route of infection (11).…”

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confidence: 99%

Parameters Underlying Successful Protection with Live Attenuated Mutants in Experimental Shigellosis

et al. 2001

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Because the use of live attenuated mutants of Shigella spp. represents a promising approach to protection against bacillary dysentery (M. E. Etherridge, A. T. M. Shamsul Hoque, and D. A. Sack, Lab. Anim. Sci. 46: 61-66, 1996), it becomes essential to rationalize this approach in animal models in order to optimize attenuation of virulence in the vaccine candidates, as well as their route and mode of administration, and to define the correlates of protection. In this study, we have compared three strains of Shigella flexneri 5-the wild-type M90T, an aroC mutant, and a double purE aroC mutant-for their pathogenicity, immunogenicity, and protective capacity. Protection against keratoconjunctivitis, induced by wild-type M90T, was used as the protection read out in guinea pigs that were inoculated either intranasally or intragastrically. Following intranasal immunization, the aroC mutant elicited weak nasal tissue destruction compared to M90T and achieved protection correlated with high levels of local anti-lipopolysaccharide immunoglobulin A (IgA), whereas the purE aroC double mutant, which also elicited weak tissue destruction, was not protective and elicited a low IgA response. Conversely, following intragastric immunization, only the M90T purE aroC double mutant elicited protection compared to both the aroC mutant and the wild-type strain. This mutant caused mild inflammatory destruction, particularly at the level of Peyer's patches, but it persisted much longer within the tissues. This could represent an essential parameter of the protective response that, in this case, did not clearly correlate with high anti-lipopolysaccharide IgA titers.

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confidence: 99%

Parameters Underlying Successful Protection with Live Attenuated Mutants in Experimental Shigellosis

et al. 2001

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“…given to adult Vietnamese volunteers (14,15). Plasmid pNV143, which carries the glucosyl transferase gene (gtr) of phage SfX, was transferred to strain SFL124 by electroporation to study the expression of group-specific antigen 7, 8.…”

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confidence: 99%

Immunogenicity of the Shigella flexneri Serotype Y (SFL124) Vaccine Strain Expressing Cloned Glucosyl Transferase Gene of Converting Bacteriophage SfX

Huan

Taylor

Lindberg

et al. 1995

Microbiology and Immunology

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The glucosyl transferase gene (gtr) from bacteriophage phage X (SfX) caused partial conversion of serotype Y (group antigen 3, 4) to X (group antigen 7, 8) when introduced into a candidate vaccine strain of Shigella flexneri serotype Y (SFL124). The gtr gene caused conversion of O-antigens but did not eliminate the adsorption of the corresponding phage SfX. The hybrid strain expressing both group antigens 7, 8 and 3, 4 showed 75% protection when immunized guinea pigs were challenged with a wild-type S. flexneri serotype X strain. No protection was observed against serotype Y challenge, although group antigen 3, 4 was detected in the LPS of the hybrid strain. This suggests the importance of O-antigen immunity in the host defense against shigellosis.

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“…In recent years, a number of attenuated Shigella strains have been constructed and evaluated as candidates for use in vaccines (12)(13)(14). These strains have been classified into two groups on the basis of the function of the mutated gene: 1) strains in which one or two genes in the metabolism have been inactivated, such as thyA, aroA, and aroD (15)(16)(17), and 2) strains harboring mutation of virG (icsA), a gene essential for cell-to-cell spreading, in addition to one of above gene mutations (18 -24). The ⌬virG strain has been widely used as an attenuated live vaccine strain or in combination with mutation in other gene(s) in several studies, including in clinical trials (14,21,(25)(26)(27).…”

Section: High Vaccine Efficacy Against Shigellosis Of Recombinant Nonmentioning

confidence: 99%

High Vaccine Efficacy against Shigellosis of Recombinant Noninvasive Shigella Mutant That Expresses Yersinia Invasin

Suzuki

Yoshikawa

Ashida

et al. 2006

The Journal of Immunology

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Live attenuated Shigella vaccines elicit protective immune responses, but involve a potential risk of inducing a strong inflammatory reaction. The bacterial invasiveness that is crucial for Ag delivery causes inflammatory destruction of infected epithelial cells and proinflammatory cell death of infected macrophages. In this study, the noninvasive Shigella mutant ΔipaB was equipped with Yersinia invasin protein, which has been shown to mediate bacterial invasion and targeting to M cells located in follicle-associated epithelium. Invasin-expressing ΔipaB (ΔipaB/inv) was internalized into epithelial cells and retained in the intraphagosomal space. ΔipaB/inv did not induce necrotic cell death of infected macrophages nor cause symptomatic damage after intranasal vaccination of mice. ΔipaB/inv was safer and more effective than the conventional live vaccine, ΔvirG. Infection by ΔipaB/inv caused polymorphonuclear neutrophil infiltration in the lung, but did not induce production of large amounts of proinflammatory cytokines. We concluded that the low experimental morbidity and high vaccine efficacy of ΔipaB/inv are primarily based on high protective immune responses, which may be enhanced by the polymorphonuclear neutrophil infiltration unaccompanied by tissue injury.

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Development of an auxotrophic oral live Shigella flexneri vaccine

Cited by 79 publications

References 20 publications

Parameters Underlying Successful Protection with Live Attenuated Mutants in Experimental Shigellosis

Parameters Underlying Successful Protection with Live Attenuated Mutants in Experimental Shigellosis

Immunogenicity of the Shigella flexneri Serotype Y (SFL124) Vaccine Strain Expressing Cloned Glucosyl Transferase Gene of Converting Bacteriophage SfX

High Vaccine Efficacy against Shigellosis of Recombinant Noninvasive Shigella Mutant That Expresses Yersinia Invasin

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