Prevention of Invasive Bacterial Diseases by Immunization with Polysaccharide-Protein Conjugates

Robbins, John B.; Schneerson, Rachel; Szu, Shousun C.; Fattom, Ali; Yang, Yanhong; Lagergård, Teresa; Chu, Chiayung; Sørensen, Uffe B. Skov

doi:10.1007/978-3-642-74529-4_18

Cited by 19 publications

(20 citation statements)

References 41 publications

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“…As a consequence, targeting capsules through active or passive immunization is a key strategy for control of many bacterial diseases. Immunity that targets bacterial capsules is, therefore, critically dependent on the interaction of antibodies with capsular antigens [26].…”

Section: Discussionmentioning

confidence: 99%

IgG Subclass and Heavy Chain Domains Contribute to Binding and Protection by mAbs to the Poly γ-D-glutamic Acid Capsular Antigen of Bacillus anthracis

et al. 2013

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Bacterial capsules are common targets for antibody-mediated immunity. The capsule of Bacillus anthracis is unusual among capsules because it is composed of a polymer of poly-γ-d-glutamic acid (γdPGA). We previously generated murine IgG3 monoclonal antibodies (mAbs) to γdPGA that were protective in a murine model of pulmonary anthrax. IgG3 antibodies are characteristic of the murine response to polysaccharide antigens. The goal of the present study was to produce subclass switch variants of the γdPGA mAbs (IgG3→IgG1→IgG2b→IgG2a) and assess the contribution of subclass to antibody affinity and protection. Subclass switch antibodies had identical variable regions but differed in their heavy chains. The results showed that a switch from the protective IgG3 to IgG1, IgG2b or IgG2a was accompanied by i) a loss of protective activity ii) a change in mAb binding to the capsular matrix, and iii) a loss of affinity. These results identify a role for the heavy chain constant region in mAb binding. Hybrid mAbs were constructed in which the CH1, CH2 or CH3 heavy chain constant domains from a non-protective, low binding IgG2b mAb were swapped into the protective IgG3 mAb. The IgG3 mAb that contained the CH1 domain from IgG2b showed no loss of affinity or protection. In contrast, swapping the CH2 or CH3 domains from IgG2b into IgG3 produced a reduction in affinity and a loss of protection. These studies identify a role for the constant region of IgG heavy chains in affinity and protection against an encapsulated bacterial pathogen.

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Section: Discussionmentioning

confidence: 99%

IgG Subclass and Heavy Chain Domains Contribute to Binding and Protection by mAbs to the Poly γ-D-glutamic Acid Capsular Antigen of Bacillus anthracis

et al. 2013

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“…We also included relevant noncapsulated strains of S. pneumoniae (SCR2) and S. aureus (Wood) to examine the influence of capsulation. It is generally accepted that noncapsulated S. pneumoniae and S. aureus strains do not cause invasive infections (31). An E. coli strain and an A. viridans strain were included as positive controls for the binding of MBL and H-ficolin, respectively.…”

Section: Discussionmentioning

confidence: 99%

Effect of Capsulation of Opportunistic Pathogenic Bacteria on Binding of the Pattern Recognition Molecules Mannan-Binding Lectin, L-Ficolin, and H-Ficolin

et al. 2005

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Mannan-binding lectin (MBL), L-ficolin, and H-ficolin are pattern recognition molecules of the innate immune system. We investigated their ability to bind to different serotypes and noncapsulated variants of two gram-positive bacterial species, Streptococcus pneumoniae and Staphylococcus aureus. MBL did not bind to capsulated S. aureus or capsulated S. pneumoniae but did bind to a noncapsulated S. aureus variant (Wood). L-ficolin bound to some capsulated S. aureus serotypes (serotypes 1, 8, 9, 11, and 12) and capsulated S. pneumoniae serotypes (11A, 11D, and 11F) but not to noncapsulated strains. H-ficolin did not bind to any of the S. pneumoniae and S. aureus serotypes included in this study but did bind to one strain of Aerococcus viridans. The concentrations of the three proteins in 97 plasma samples were estimated. The median concentrations were 0.8 g per ml for MBL, 3.3 g per ml for L-ficolin, and 18.4 g per ml for H-ficolin.

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“…Capsular antibodies are protective against capsulated pathogens like pneumococci, meningococci, and Haemophilus influenzae type b [2]. A challenge in developing a Klebsiella CPS-based vaccine is the large number of K antigens (77 K serotypes and many non-typable strains), however only some are known to be associated with human diseases [3].…”

mentioning

confidence: 99%

The capsular polysaccharide and lipopolysaccharide structures of two carbapenem resistant Klebsiella pneumoniae outbreak isolates

Kübler-Kiełb

Vinogradov

et al. 2013

Carbohydrate Research

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Carbapenem resistant Klebsiella pneumoniae (CRKP) are isolated with increasing frequency, especially from immunocompromized patients. The capsular polysaccharide (CPS) types of CPKP were not determined. Investigation of two CRKP isolates from a 2011 outbreak at the Clinical Center, the National Institutes of Health, identified a new capsular type shared by the two isolates, similar to K. pneumonia K19 and K34 but structurally different than any published K. pneumoniae CPS repeating unit: The LPS of the two isolates was found to have no O-specific polysaccharide and the chemical structure of the core oligosaccharides agreed with published data. If this structure type will be prevalent among CPKP isolates, our findings could facilitate rapid diagnosis and help develop new therapeutic solutions to this antibiotic resistant pathogen.

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Prevention of Invasive Bacterial Diseases by Immunization with Polysaccharide-Protein Conjugates

Cited by 19 publications

References 41 publications

IgG Subclass and Heavy Chain Domains Contribute to Binding and Protection by mAbs to the Poly γ-D-glutamic Acid Capsular Antigen of Bacillus anthracis

IgG Subclass and Heavy Chain Domains Contribute to Binding and Protection by mAbs to the Poly γ-D-glutamic Acid Capsular Antigen of Bacillus anthracis

Effect of Capsulation of Opportunistic Pathogenic Bacteria on Binding of the Pattern Recognition Molecules Mannan-Binding Lectin, L-Ficolin, and H-Ficolin

The capsular polysaccharide and lipopolysaccharide structures of two carbapenem resistant Klebsiella pneumoniae outbreak isolates

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