Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1–4-year-old Israeli children

Passwell, J H; Ashkenzi, Shai; Banet-Levi, Yonit; Ramon-Saraf, Reut; Farzam, Nahid; Lerner‐Geva, Liat; Even-Nir, Hadas; Yerushalmi, Baruch; Chu, Chiayung; Shiloach, Joseph; Robbins, John B.; Schneerson, Rachel

doi:10.1016/j.vaccine.2009.12.050

Cited by 149 publications

(143 citation statements)

References 29 publications

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“…A Shigella conjugate vaccine has been shown to elicit significant levels of LPS IgG in children as young as 1 year (52), although this did not translate into protective efficacy for those younger than the age of 3 years (51). We have shown, in the neonatal mouse model, that transcutaneous administration of a neoglycoconjugate vaccine containing a hexasaccharide of V. cholerae OSP was effective in the induction of LPS and vibriocidal antibodies in orally primed mice (44).…”

Section: Discussionmentioning

confidence: 97%

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Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Leung

Uddin

et al. 2013

Clin Vaccine Immunol

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g Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n ‫؍‬ 15), young children (24 to 59 months, n ‫؍‬ 14), and older children (5 to 15 years, n ‫؍‬ 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.

show abstract

Section: Discussionmentioning

confidence: 97%

“…OSP-protein conjugate vaccines are under development for a number of diarrheal diseases (49)(50)(51). A Shigella conjugate vaccine has been shown to elicit significant levels of LPS IgG in children as young as 1 year (52), although this did not translate into protective efficacy for those younger than the age of 3 years (51).…”

Section: Discussionmentioning

confidence: 99%

Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Leung

Uddin

et al. 2013

Clin Vaccine Immunol

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“…The study demonstrated that the S. sonnei conjugate had a protective efficacy of 71 % in 3-4 year-old children, but not in younger ones (Passwell et al, 2010).…”

Section: Inactivated Shigella Vaccine Candidatementioning

confidence: 85%

“…The efficacy of these conjugates was examined where a randomized, double-blind efficacy study was done in 1-4-year-old children at 15 sites throughout Israel (Passwell et al, 2010). The study demonstrated that the S. sonnei conjugate had a protective efficacy of 71 % in 3-4 year-old children, but not in younger ones (Passwell et al, 2010).…”

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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“…Although, the efficacy for S. flexneri was only 7.9% (95% CI: -153.2-66.5). 22 The main challenge to this vaccine strategy is to provide broad protection against the most common Shigella strains with only one vaccine, as immunogenicity tends to be strain and serotype specific. Given this, synthetic O antigen-derived carbohydrates seem to be promising candidates, first, to reduce the LPS-associated toxicity and second, as a strategy for developing a multivalent conjugate vaccine, which is still required to confer broad protection against different Shigella serotypes (see below).…”

Section: Shigella Sppmentioning

confidence: 99%

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

O’Ryan

Vidal

Canto

et al. 2015

Human Vaccines & Immunotherapeutics

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Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1–4-year-old Israeli children

Abstract: Shigella conjugates are safe and immunogenic in 1-4 years old. The S. sonnei conjugate elicited 71.1% efficacy in the 3-4 years old and can be predicted to be efficacious in individuals older than 3 years of age. These results urge studies with our improved conjugates.

Cited by 149 publications

References 29 publications

Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

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

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

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