Shigella lipopolysaccharide antibodies in pediatric populations

Passwell, J H; Freier, S; Shor, R; Farzam, Nahid; Block, Colin; Lison, M; Shiff, Eyal; Ashkenazi, Shai

doi:10.1097/00006454-199510000-00008

Cited by 17 publications

(19 citation statements)

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“…Our choice for the five conjugates was based on their immunogenicity in young outbred mice (41). The three S. sonnei O-SP conjugates, S. sonnei-CRM9, S. sonnei-CRM9 succ , and S. sonnei-rEPA succ , induced similar IgG anti-LPS responses in adults.…”

Section: Discussionmentioning

confidence: 99%

“…(i) Correlation was found between the level of IgG LPS antibodies and resistance to shigellosis among Israeli solders (11,14). (ii) There is an inverse relationship between the age incidence of shigellosis and the presence of IgG antibodies to the LPS of Shigella (41,46). The peak incidence of shigellosis is in children and young adults; the disease is rare in infants and in older adults (14,15,20,21,23,26,28,38,46).…”

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confidence: 99%

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Safety and Immunogenicity of ImprovedShigellaO-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel

et al. 2001

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Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) ofShigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4-to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigella conjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonnei and Shigella flexneri 2a bound to succinylated mutant Pseudomonas aeruginosa exotoxin A (rEPA succ ) or native or succinylated Corynebacterium diphtheriae toxin mutant (CRM9 or CRM9 succ ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9, S. sonnei-CRM9 succ , and S. sonnei-rEPA succ elicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P < 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P < 0.0001). GM IgG anti-LPS levels elicited by S. flexneri 2a-rEPA succ were significantly higher than those elicited by S. flexneri 2a-rCRM9 succ at all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P < 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigella conjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678-3687, 1993). Based on these data, we chose S. sonnei-CRM9 and S. flexneri 2a-rEPA succ for evaluation in children.

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Section: Discussionmentioning

confidence: 99%

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Safety and Immunogenicity of ImprovedShigellaO-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel

et al. 2001

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“…However, most anti-LPS antibodies in normal human sera have likely developed after exposure to antigen, either from pathogenic or commensal organisms ("naturally induced" antibodies) (14,23,40) or as a result of immunization (2,11,12,39,54,65).…”

Section: Discussionmentioning

confidence: 99%

Importance of Antibodies to Lipopolysaccharide in Natural and Vaccine-Induced Serum Bactericidal Activity against Neisseria meningitidis Group B

et al. 2011

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Analysis of the specificity of bactericidal antibodies in normal, convalescent, and postvaccination human sera is important in understanding human immunity to meningococcal infections and can aid in the design of an effective group B vaccine. A collection of human sera, including group C and group B convalescent-phase sera, normal sera with naturally occurring cross-reactive bactericidal activity, and some postvaccination sera, was analyzed to determine the specificity of cross-reactive bactericidal antibodies. Analysis of human sera using a bactericidal antibody depletion assay demonstrated that a significant portion of the bactericidal activity could be removed by purified lipopolysaccharide (LPS). LPS homologous to that expressed on the bactericidal test strain was most effective, but partial depletion by heterologous LPS suggested the presence of antibodies with various degrees of cross-reactivity. Binding of anti-L3,7 LPS bactericidal antibodies was affected by modification of the core structure, suggesting that these functional antibodies recognized epitopes consisting of both core structures and lacto-N-neotetraose (LNnT). When the target strain was grown with 5-cytidinemonophospho-N-acetylneuraminic acid (CMP-NANA) to increase LPS sialylation, convalescentphase serum bactericidal titers were decreased by only 2-to 4-fold, and most remaining bactericidal activity was still depleted by LPS. Highly sialylated LPS was ineffective in depleting bactericidal antibodies. We conclude that natural infections caused by strains expressing L3,7 LPS induce persistent, protective bactericidal antibodies and appear to be directed against nonsialylated bacterial epitopes. Additionally, subsets of these bactericidal antibodies are cross-reactive, binding to several different LPS immunotypes, which is a useful characteristic for an effective group B meningococcal vaccine antigen.

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“…LPS-based vaccines were developed in concert with case control and prospective studies demonstrating an association between serum LPS IgG antibodies and serotypespecific protection against shigellosis (Cohen et al, 1991;Passwell et al, 1995).…”

Section: Inactivated Shigella Vaccine Candidatementioning

confidence: 99%

Modern Aspects on <i>Shigella</i> Pathogenecity and Vaccine Development - A Review

Pal¹

2014

ILNS

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Shigella species are intracytosolic Gram-negative invasive enteropathogenic bacteria, causing the rupture, invasion and inflammatory destruction of the human colonic epithelium. They utilize the host cytoskeletal components to form propulsive actin tails. The so-called invasive phenotype of Shigella is linked to expression of a type III secretory system (TTSS) injecting effector proteins into the epithelial cell membrane and cytoplasm, thereby inducing local but massive changes in the cell cytoskeleton that lead to bacterial internalization into non-phagocytic intestinal epithelial cells. The molecular and cellular bases of this invasive phenotype essentially encompass crossing of the epithelial lining, apoptotic killing of macrophages, entry into epithelial cells, and escape into the cytoplasm, followed by cell-to-cell spread. Intracellular colonization is likely to protect the microorganisms from killing by humoral and cellular effectors of the innate immune response. Concurrently, the capacity of Shigella to reprogram invaded epithelial cells to produce proinflammatory mediators plays a major role in the strong inflammatory profile of the disease. This profile is likely to impact on the nature and quality of the adaptive response, which is dominated by humoral protection at the mucosal level. In recent years, a large amount of information has been generated regarding the host, pathogen and environmental factors that impact the pathogenesis of shigellosis at the cellular and molecular level. This review summarizes what is currently known about Shigella, detailing those factors that contribute to pathogenesis and examining the current progress in the development of a vaccine.

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Shigella lipopolysaccharide antibodies in pediatric populations

Cited by 17 publications

References 0 publications

Safety and Immunogenicity of ImprovedShigellaO-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel

Safety and Immunogenicity of ImprovedShigellaO-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel

Importance of Antibodies to Lipopolysaccharide in Natural and Vaccine-Induced Serum Bactericidal Activity against Neisseria meningitidis Group B

Modern Aspects on <i>Shigella</i> Pathogenecity and Vaccine Development - A Review

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