Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate

Kabanova, Anna; Margarit, Immaculada; Berti, Francesco; Romano, Maria; Grandi, Guido; Bensi, Giuliano; Chiarot, Emiliano; Proietti, Daniela; Swennen, Erwin; Cappelletti, Emilia; Fontani, Paola; Casini, Daniele; Adamo, Roberto; Pinto, Vittoria; Skibinski, David; Capo, Sabrina; Buffi, Giada; Gallotta, Marilena; Christ, William J.; Campbell, Stewart; Pena, John; Seeberger, Peter H.; Rappuoli, Rino; Costantino, Paolo

doi:10.1016/j.vaccine.2010.09.018

Cited by 80 publications

(92 citation statements)

References 54 publications

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“…Due to its prominence in the GAS cell wall and its conservation across all GAS strains, the GAC has been considered as a potential antigen for a universal GAS vaccine. Passive and active mouse immunization studies with protein conjugate vaccines using purified or synthetic versions of the WT GAC show significant efficacy against multiple GAS serotypes (Kabanova et al, 2010; Sabharwal et al, 2006). Moreover, anti-GAC antibodies are detected in human serum, high titers correlate with decreased colonization in children (Sabharwal et al, 2006), and peak around age 17 correlating to dropping GAS infection rates after this age (Zimmerman et al, 1971).…”

Section: Introductionmentioning

confidence: 99%

The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design

Sorge

Cole

Kuipers

et al. 2014

Cell Host & Microbe

124

251

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SUMMARY Group A Streptococcus (GAS) is a leading cause of infection-related mortality in humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological function has been attributed to this conserved antigen. Here we identify and characterize the GAC biosynthesis genes,gacA-L. An isogenic mutant of the glycosyltransferase gacI, which is defective for GlcNAcside chain addition, is attenuated for virulence in two infection models, in association with increased sensitivity to neutrophil killing, platelet-derived antimicrobials in serum and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC lacking the GlcNAc side chain and containing only polyrhamnose promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge after passive immunization. Thus, the Lancefield antigen plays a functional role in GAS pathogenesis and its understanding has implications for vaccine development.

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Section: Introductionmentioning

confidence: 99%

The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design

Sorge

Cole

Kuipers

et al. 2014

Cell Host & Microbe

124

251

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“…Regardless of serotype, S. pyogenes (Group A streptococcus, GAS) expresses a cell wall polysaccharide with a helical rhamnose backbone decorated with repetitive terminal GlcNAc residues (38) that is highly immunogenic in mice and humans. Infection with GAS induces antibodies against GlcNAc (25), and these antibodies are somewhat protective in mouse models of GAS infection (66–68). The development of a GlcNAc-based vaccine for GAS infection has been proposed for many years.…”

Section: Introductionmentioning

confidence: 99%

Immunological Outcomes of Antibody Binding to Glycans Shared between Microorganisms and Mammals

Patel

Kearney

2016

The Journal of Immunology

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Glycans constitute basic cellular components of living organisms across biological kingdoms (Table 1), and glycan-binding antibodies participate in many cellular interactions during immune defense against pathogenic organisms (Figure 1). Glycan epitopes are expressed as carbohydrate-only entities or as oligomers or polymers on proteins and lipids. Such epitopes on glycoproteins may be formed by post-translational modifications or neoepitopes resulting from metabolic/catabolic processes, and can be altered during inflammation. Pathogenic organisms can display host-like glycans to evade the host immune response. However, antibodies to glycans, shared between microorganisms and the host, exist naturally. These antibodies are able to not only protect against infectious disease, but are also involved in host housekeeping functions and can suppress allergic disease. Despite the reactivity of these antibodies to glycans shared between microorganisms and host, diverse tolerance-inducing mechanisms permit the B cell precursors of these antibody-secreting cells to exist within the normal B cell repertoire.

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“…The first dilution in the linear range of response which gave an OD 405 nm <= 2.5 was given 1,000 AU, then 500 AU, 250 AU, 125 AU, 62.5 AU from the second to the fifth two-fold dilution point. The standard curve was fitted to a function, which was used to convert the absorbance of sera dilutions into AU [28,55,56]. Sera dilution points with OD 405 nm >= 0.2 and <= 2.5 were considered in the calculation.…”

Section: Methodsmentioning

confidence: 99%

Protective Activity of the CnaBE3 Domain Conserved among Staphylococcus aureus Sdr Proteins

et al. 2013

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Staphylococcus aureus is an opportunistic pathogen, commensal of the human skin and nares, but also responsible for invasive nosocomial as well as community acquired infections. Staphylococcus aureus adheres to the host tissues by means of surface adhesins, such as SdrC, SdrD, and SdrE proteins. The Sdr family of proteins together with a functional A domain, contain respectively two, three or five repeated sequences called B motifs which comprise the CnaB domains. SdrD and SdrE proteins were reported to be protective in animal models against invasive diseases or lethal challenge with human clinical S. aureus isolates. In this study we identified a 126 amino acid sequence containing a CnaB domain, conserved among the three Sdr proteins. The three fragments defined here as CnaBC2, D5 and E3 domains even though belonging to phylogenetically distinct strains, displayed high sequence similarity. Based on the sequence conservation data, we selected the CnaBE3 domain for further analysis and characterization. Polyclonal antibodies raised against the recombinant CnaBE3 domain recognized SdrE, SdrC and SdrD proteins of different S. aureus lineages. Moreover, we demonstrated that the CnaBE3 domain was expressed in vivo during S. aureus infections, and that immunization of this domain alone significantly reduces the bacterial load in mice challenged with S. aureus. Furthermore, we show that the reduction of bacteria by CnaBE3 vaccination is due to functional antibodies. Finally, we demonstrated that the region of the SdrE protein containing the CnaBE3 domain was resistant to trypsin digestion, a characteristic often associated with the presence of an isopeptide bond.

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Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate

Cited by 80 publications

References 54 publications

The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design

The Classical Lancefield Antigen of Group A Streptococcus Is a Virulence Determinant with Implications for Vaccine Design

Immunological Outcomes of Antibody Binding to Glycans Shared between Microorganisms and Mammals

Protective Activity of the CnaBE3 Domain Conserved among Staphylococcus aureus Sdr Proteins

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