Epitope Recognition of a Monoclonal Antibody Raised against a Synthetic Glycerol Phosphate Based Teichoic Acid

Berni, Francesca; Kalfopoulou, Ermioni; Cardells, Ana M Gimeno; Carboni, Filippo; Es, Daan van der; Romero-Saavedra, Felipe; Laverde, Diana; Miklić, Karmela; Malić, Suzana; Roviš, Tihana Lenac; Jonjić, Stipan; Ali, Sara; Overkleeft, Herman S.; Hokke, Cornelis H.; Diepen, Angela van; Adamo, Roberto; Jiménez‐Barbero, Jesús; Marel, Gijsbert A. van der; Hüebner, Johannes; Codée, Jeroen D. C.

doi:10.1021/acschembio.1c00422

Cited by 6 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently developed a TA microarray to evaluate antibody binding to a large set of poly(glycerolphosphate) (GroP)-based lipoteichoic acid (LTA) oligomers . We have applied this TA microarray to map the recognition of different mAbs as well as polyclonal sera. ,, To start our binding studies of the mAbs 4497 and 4461, we here generated an array presenting both WTA and LTA fragments (Figure ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Antibody Recognition of Different Staphylococcus aureus Wall Teichoic Acid Glycoforms

et al. 2022

View full text Add to dashboard Cite

Wall teichoic acids (WTAs) are glycopolymers decorating the surface of Gram-positive bacteria and potential targets for antibodymediated treatments against Staphylococcus aureus, including methicillinresistant (MRSA) strains. Through a combination of glycan microarray, synthetic chemistry, crystallography, NMR, and computational studies, we unraveled the molecular and structural details of fully defined synthetic WTA fragments recognized by previously described monoclonal antibodies (mAbs 4461 and 4497). Our results unveiled the structural requirements for the discriminatory recognition of αand β-GlcNAcmodified WTA glycoforms by the complementarity-determining regions (CDRs) of the heavy and light chains of the mAbs. Both mAbs interacted not only with the sugar moiety but also with the phosphate groups as well as residues in the ribitol phosphate (RboP) units of the WTA backbone, highlighting their significant role in ligand specificity. Using elongated WTA fragments, containing two sugar modifications, we also demonstrated that the internal carbohydrate moiety of α-GlcNAc-modified WTA is preferentially accommodated in the binding pocket of mAb 4461 with respect to the terminal moiety. Our results also explained the recently documented cross-reactivity of mAb 4497 for β-1,3/β-1,4-GlcNAc-modified WTA, revealing that the flexibility of the RboP backbone is crucial to allow positioning of both glycans in the antibody binding pocket.

show abstract

Section: Resultsmentioning

confidence: 99%

“…18 We have applied this TA microarray to map the recognition of different mAbs as well as polyclonal sera. 15,19,20 To start our binding studies of the mAbs 4497 and 4461, we here generated an array presenting both WTA and LTA fragments (Figure 3).…”

Section: ■ Introductionmentioning

confidence: 99%

Antibody Recognition of Different Staphylococcus aureus Wall Teichoic Acid Glycoforms

et al. 2022

View full text Add to dashboard Cite

show abstract

“…A recent study used microarrays comprised of various synthetic WTA glycans to identify the recognition motif of a mAb (WH7.01) generated by immunization of mice with WH7, a synthetic version of a GroP WTA hexamer. 151 Screening of WH7.01 with these WTA microarrays-in combination with ELISA, SPR analyses, and STD-NMR spectroscopy-found that this mAb recognized GroPbased WTA fragments but not similar RboP-containing WTAs. 151 This indicates that the GroP moiety is the main recognition element for this anti-WTA mAb.…”

Section: Antibodies To Bacterial Glycansmentioning

confidence: 99%

“…151 Screening of WH7.01 with these WTA microarrays-in combination with ELISA, SPR analyses, and STD-NMR spectroscopy-found that this mAb recognized GroPbased WTA fragments but not similar RboP-containing WTAs. 151 This indicates that the GroP moiety is the main recognition element for this anti-WTA mAb. 151 Glycan microarrays have also been used to assess antibody recognition of the capsular polysaccharides (CPSs) of the Grampositive bacteria S. pneumoniae [152][153][154][155] Clostridium difficile, and Bacillus anthracis.…”

Section: Antibodies To Bacterial Glycansmentioning

confidence: 99%

Serum antibody screening using glycan arrays

Marglous,

Brown,

Padler-Karavani

et al. 2024

Chem. Soc. Rev.

View full text Add to dashboard Cite

show abstract

“…The serum raised against the native LTA bound the opposite stereochemistry GroP better as it better resembles how LTA is anchored in the bacterial cell wall. A follow-up study elucidated the interactions of a mAb generated against (52) and a library of LTA structures through a combination of glycan array, ELISA, SPR-analyses, and STD-NMR spectroscopy to show that the number of GroP residues was important for affinity of the mAb and that binding was indirectly effected by the presence of the glucose residue . This study confirmed the importance of the backbone chirality.…”

Section: Emerging Amr Targetsmentioning

confidence: 99%

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Bino

Østerlid

et al. 2022

Chem. Rev.

Self Cite

View full text Add to dashboard Cite

Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides diff icile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus inf luenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure−immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.

show abstract

Epitope Recognition of a Monoclonal Antibody Raised against a Synthetic Glycerol Phosphate Based Teichoic Acid

Cited by 6 publications

References 33 publications

Antibody Recognition of Different Staphylococcus aureus Wall Teichoic Acid Glycoforms

Antibody Recognition of Different Staphylococcus aureus Wall Teichoic Acid Glycoforms

Serum antibody screening using glycan arrays

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Contact Info

Product

Resources

About