Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM197 conjugate vaccine co-localizes with MHC II on the antigen processing cell surface

Lai, Zengzu; Schreiber, John R.

doi:10.1016/j.vaccine.2009.03.064

Cited by 44 publications

(26 citation statements)

References 32 publications

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“…Alternatively, the frequent colonization of humans with these encapsulated bacteria may result in the development of CPS-specific memory B cells, with the assistance of bacterial proteins and TLR agonists. It is well known that reimmunization of mice or humans following proteinconjugated CPS vaccine immunization induces a strong booster response, suggesting that the activation of CPS-specific memory B cells does not require T cell help (39). Similarly, humans immunized with CPS vaccine may be developing Ab response against CPS because CPS-specific memory B cells may not be as dependent on BAFF/APRIL stimulation as the naive B cells.…”

Section: Discussionmentioning

confidence: 99%

“…A key difference between unconjugated CPS from the conjugate vaccine is that the conjugate vaccine induces a T celldependent immune response to CPS Ags (39,45). Therefore, it is likely that in conjugate MCPS vaccines T cell interaction with B cells through the costimulatory molecules and possibly cytokines ablates the suppressive effect of MCPS on B cells.…”

Section: Discussionmentioning

confidence: 99%

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Suppressive Effect of Bacterial Polysaccharides on BAFF System Is Responsible for Their Poor Immunogenicity

Kanswal

Katsenelson

Allman

et al. 2011

The Journal of Immunology

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Capsular polysaccharides of encapsulated bacteria are weakly immunogenic T cell-independent type 2 (TI-2) Ags. Recent findings suggest that BAFF system molecules have a critical role in the development of Ab responses against TI-2 Ags. In this study, we investigated the effect of bacterial polysaccharides on B cell responses to BAFF and a proliferation-inducing ligand (APRIL). We determined that B cells exposed to meningococcal type C polysaccharide (MCPS) or group B Streptococcus serotype V (GBS-V) were unresponsive to BAFF- and APRIL-induced Ig secretion. Moreover, MCPS and GBS-V strongly downregulated transmembrane activator and calcium-modulator and cyclophilin ligand interactor, the BAFF and APRIL receptor that is responsible for Ab development against TI-2 Ags. Interestingly, (4-hydroxy-3-nitrophenyl)acetyl-Ficoll (NP-Ficoll), a prototype TI-2 Ag, did not manifest a suppressive effect on B cells. Paradoxically, whereas GBS-V and MCPS inhibited IFN-γ–induced BAFF production from dendritic cells, NP-Ficoll strongly increased BAFF secretion. TLR 9 agonist CpG deoxyoligonucleotide (ODN) was able to reverse the MCPS-mediated transmembrane activator and calcium-modulator and cyclophilin ligand interactor suppression but could not rescue the Ig secretion in BAFF- or APRIL-stimulated B cells. In support of these in vitro observations, it was observed that CpG ODN could help augment the Ab response against NP in mice immunized with a CpG ODN-containing NP-Ficoll vaccine but exhibited only marginal adjuvant activity for MCPS vaccine. Collectively, these results suggest a mechanism for the weak immunogenicity of bacterial polysaccharides and explain the previously observed differences between bacterial polysaccharide and NP-Ficoll immunogenicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Suppressive Effect of Bacterial Polysaccharides on BAFF System Is Responsible for Their Poor Immunogenicity

Kanswal

Katsenelson

Allman

et al. 2011

The Journal of Immunology

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“…Upon MHC class II peptide recognition by the T-cell receptor, T cells become activated and secrete cytokines that provide "help" for the induction of B-cell affinity maturation and antibody isotype switching to produce higher affinity antibodies against the polysaccharide antigen. This hypothesis is supported by the fact that coadministration of polysaccharide and protein that are not covalently attached does not result in T-cell activation (12,13). These data, however, do not rule out the possibility that the polysaccharide and protein only have to be close enough in proximity to be taken up by the same B cell and do not have to be covalently attached to achieve T-cell activation.…”

mentioning

confidence: 98%

Conjugate-like immunogens produced as protein capsular matrix vaccines

Thanawastien¹,

Cartee²,

Griffin³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Capsular polysaccharides are the primary antigenic components involved in protective immunity against encapsulated bacterial pathogens. Although immunization of adolescents and adults with polysaccharide antigens has reduced pathogen disease burden, pure polysaccharide vaccines have proved ineffective at conferring protective immunity to infants and the elderly, age cohorts that are deficient in their adaptive immune responses to such antigens. However, T-cell–independent polysaccharide antigens can be converted into more potent immunogens by chemically coupling to a “carrier protein” antigen. Such “conjugate vaccines” efficiently induce antibody avidity maturation, isotype switching, and immunological memory in immunized neonates. These immune responses have been attributed to T-cell recognition of peptides derived from the coupled carrier protein. The covalent attachment of polysaccharide antigens to the carrier protein is thought to be imperative to the immunological properties of conjugate vaccines. Here we provide evidence that covalent attachment to carrier proteins is not required for conversion of T-independent antigens into T-dependent immunogens. Simple entrapment of polysaccharides or a d-amino acid polymer antigen in a cross-linked protein matrix was shown to be sufficient to produce potent immunogens that possess the key characteristics of conventional conjugate vaccines. The versatility and ease of manufacture of these antigen preparations, termed protein capsular matrix vaccines (PCMVs), will likely provide improvements in the manufacture of vaccines designed to protect against encapsulated microorganisms. This in turn could improve the availability of such vaccines to the developing world, which has shown only a limited capacity to afford the cost of conventional conjugate vaccines.

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“…However, information regarding the exact mechanisms of the immune response to oligosaccharide structures is relatively scarce, although certainly O-glycopeptides can be presented in an MHC-dependent manner [6], and the polysaccharide portion of a glycoconjugate vaccine colocalizes with MHC class II molecules [7]. Studies on model N-glycosylated proteins would indicate that the oligosaccharide is removed before MHC presentation [8]; on the other hand, MHC-independent presentation is suggested to occur in the case of some glycoconjugates [9,10].…”

Section: The Immune Response To Glycansmentioning

confidence: 99%

Glycomarkers in parasitic infections and allergy

Hoffmann‐Sommergruber

Paschinger

Wilson

2011

Biochemical Society Transactions

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Both helminth infections and contact with allergens result in development of a Th2 type of immune response in the affected individual. In this context, the hygiene hypothesis suggests that reduced prevalence of parasitic infections and successful vaccination strategies are causative for an increase of allergies in industrialized countries. It is therefore of interest to study glycans and their role as immunogenic structures in both parasitic infections and allergies. In the present paper we review information on the different types of glycan structure present in proteins from plant and animal food, insect venom and helminth parasites, and their role as diagnostic markers. In addition, the application of these glycan structures as immunomodulators in novel immunotherapeutic strategies is discussed.

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Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM197 conjugate vaccine co-localizes with MHC II on the antigen processing cell surface

Cited by 44 publications

References 32 publications

Suppressive Effect of Bacterial Polysaccharides on BAFF System Is Responsible for Their Poor Immunogenicity

Suppressive Effect of Bacterial Polysaccharides on BAFF System Is Responsible for Their Poor Immunogenicity

Conjugate-like immunogens produced as protein capsular matrix vaccines

Glycomarkers in parasitic infections and allergy

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