Serum Antibodies to Lipopolysaccharide and Natural Immunity to Shigellosis in an Israeli Military Population

Cohen, Dani; Green, Manfred S.; Block, Colin; Rouach, Tsvi; Ofek, Itzhak

doi:10.1093/infdis/157.5.1068

Cited by 149 publications

(126 citation statements)

References 12 publications

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“…regimen, only M90T and M90T purE aroC stimulated significant levels of anti-LPS IgG, perhaps suggesting that these antibodies influence protection. In humans, a significant correlation between anti-LPS IgG and resistance to shigellosis was observed (5,6), and Shigella-LPS conjugates (composed of the O-specific polysaccharides conjugated to a carrier protein) are protective and induce high levels of anti-LPS IgG (7). Briefly, in the model of i.n.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Parameters Underlying Successful Protection with Live Attenuated Mutants in Experimental Shigellosis

et al. 2001

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“…On the basis of this concept, NICHD investigators have developed parenteral conjugate vaccines that consist of O polysaccharides derived from the LPS of relevant Shigella serotypes covalently linked to a carrier protein (Pseudomonas aeruginosa exotoxin A (PsA) or CRM9-mutant diphtheria toxin). Data supporting the concept that serum IgG anti-O-antigen antibodies correlate with (and might mediate) protection come from the seroepide-miological studies of Cohen and colleagues 111,112 . Baseline serum specimens were obtained from Israeli military conscripts upon deployment to training bases where they were exposed to a high risk of shigellosis 111,112 .…”

Section: Shigella Conjugate Vaccinesmentioning

confidence: 99%

“…Data supporting the concept that serum IgG anti-O-antigen antibodies correlate with (and might mediate) protection come from the seroepide-miological studies of Cohen and colleagues 111,112 . Baseline serum specimens were obtained from Israeli military conscripts upon deployment to training bases where they were exposed to a high risk of shigellosis 111,112 . The rates of S. sonnei and S. flexneri 2a disease were significantly lower in individuals who had elevated non-IgM anti-O-antigen titres at baseline.…”

Section: Shigella Conjugate Vaccinesmentioning

confidence: 99%

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

et al. 2007

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More than 50 years of research has yielded numerous Shigella vaccine candidates that have exemplified both the promise of vaccine-induced prevention of shigellosis and the impediments to developing a safe and effective vaccine for widespread use, a goal that has yet to be attained. This Review discusses the most advanced strategies for Shigella vaccine development, the immune responses that are elicited following disease or vaccination, the factors that have accelerated or impeded Shigella vaccine development and our ideas for the way forward.At the end of the 19th century, as epidemics of bacillary dysentery accompanied by high mortality spread across Japan, the young microbiologist Kiyoshi Shiga examined dysenteric stools and isolated a bacterium that was agglutinated by serum from convalescent patients but not from patients with acute disease [1][2][3] (FIG. 1). That bacterium -known today as Shigella dysenteriae 1 -was the first identified member of the genus Shigella. Four Correspondence to M.L. mlevine@medicine.umaryland.edu. Competing interests statement:The authors declare no competing financial interests. Links NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptShigella species (or groups) are now recognized: S. dysenteriae (group A), which has 15 serotypes; Shigella flexneri (group B), which has 14 classical serotypes and subserotypes; Shigella boydii (group C), which has 20 serotypes; and Shigella sonnei (group D), which has single serotype 4 (TABLE 1).There has been resurgent interest in Shigella as a human pathogen, driven by the availability of more precise data on the disease burden 5-8 , emerging antibiotic resistance 9,10 and the fact that mucosally invasive Shigella, which often cause dysentery (gross blood in diarrhoeal stools), are less amenable to the salutary effects of oral rehydration than non-invasive pathogens that cause watery diarrhoea, such as Vibrio cholerae and enterotoxigenic Escherichia coli. The target populations for the use of Shigella vaccines include infants and young children in developing countries (in which the peak incidence occurs at 12-47 months of age and the S. flexneri serotypes predominate) 5-7 .S. dysenteriae 1, which produces Shiga toxin and typically carries R factors that encode resistance to multiple antibodies, waxes and wanes as a cause of epidemic severe disease in the world's least developed countries [11][12][13][14] Few bacterial pathogens have had their pathogenesis or interactions with mammalian tissues elucidated so precisely at the cellular and subcellular levels as Shigella spp. 20,21 Nevertheless, progress in attaining safe and effective Shigella vaccines has faltered. Herein, we review recent and old clinical trials that have evaluated the safety, immunogenicity and efficacy of candidate Shigella vaccines. We relate the bassis for the most popular strategies (BOX 2), the relevance of the different immune responses measured, the factors that have favoured or impeded vaccine development and, most importantly, the less...

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“…and intragastric (58). A significant correlation between anti-LPS IgG and resistance to shigellosis has been reported in humans (59,60). Although the above findings may suggest that production of anti-LPS IgG and IgA is associated with protection, the role of serum Abs against Shigella LPS in protective immunity is still unclear.…”

Section: Discussionmentioning

confidence: 98%

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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Serum Antibodies to Lipopolysaccharide and Natural Immunity to Shigellosis in an Israeli Military Population

Cited by 149 publications

References 12 publications

Parameters Underlying Successful Protection with Live Attenuated Mutants in Experimental Shigellosis

Parameters Underlying Successful Protection with Live Attenuated Mutants in Experimental Shigellosis

Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road

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

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