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Micoli F, Alfini R, Di Benedetto R, Necchi F, Schiavo F, Mancini F, Carducci M, Oldrini D, Pitirollo O, Gasperini G, Balocchi C, Bechi N, Brunelli B, Piccioli D, Adamo R
Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models
Frontiers in Immunology 12 (2021)
719315
Neisseria meningitidis C
(NCBI TaxID 135720,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: infection due to Neisseria meningitidis [ICD11:
XN1DV 
]
NCBI PubMed ID: 34594333Publication DOI: 10.3389/fimmu.2021.719315Journal NLM ID: 101560960Publisher: Lausanne: Frontiers Research Foundation
Correspondence: Francesca Micoli <francesca.x.micoli
gsk.com>
Institutions: GSK Vaccines Institute for Global Health (GVGH), Siena, Italy, GSK, Research Centre, Siena, Italy
Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen presentation with the immunopotentiator effect of the Toll-like receptor agonists naturally present on these systems. In this context, we are testing Generalized Modules for Membrane Antigens (GMMA), OMVs naturally released from Gram-negative bacteria mutated to increase blebbing, as carrier for polysaccharides. Here, we investigated the impact of saccharide length, density, and attachment site on the immune response elicited by GMMA in animal models, using a variety of structurally diverse polysaccharides from different pathogens (i.e., Neisseria meningitidis serogroup A and C, Haemophilus influenzae type b, and streptococcus Group A Carbohydrate and Salmonella Typhi Vi). Anti-polysaccharide immune response was not affected by the number of saccharides per GMMA particle. However, lower saccharide loading can better preserve the immunogenicity of GMMA as antigen. In contrast, saccharide length needs to be optimized for each specific antigen. Interestingly, GMMA conjugates induced strong functional immune response even when the polysaccharides were linked to sugars on GMMA. We also verified that GMMA conjugates elicit a T-dependent humoral immune response to polysaccharides that is strictly dependent on the nature of the polysaccharide. The results obtained are important to design novel glycoconjugate vaccines using GMMA as carrier and support the development of multicomponent glycoconjugate vaccines where GMMA can play the dual role of carrier and antigen. In addition, this work provides significant insights into the mechanism of action of glycoconjugates.
polysaccharide, vaccine, glycoconjugate, GMMA, carrier protein
Structure type: homopolymer
Location inside paper: Fig. 7A
Trivial name: polysialic acid
Compound class: CPS
Contained glycoepitopes: IEDB_136794,IEDB_146100,IEDB_149174,IEDB_150075,IEDB_150759,IEDB_910420,SB_170,SB_171,SB_172,SB_84
Methods: chemical analysis, ELISA, biological assays, HPAEC-PAD, immunization, conjugation, HPLC-SEC, reductive amination, RP-UPLC
Related record ID(s): 9699, 10909
NCBI Taxonomy refs (TaxIDs): 135720Reference(s) to other database(s): GTC:G76437DD
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Micoli F, Alfini R, Di Benedetto R, Necchi F, Schiavo F, Mancini F, Carducci M, Oldrini D, Pitirollo O, Gasperini G, Balocchi C, Bechi N, Brunelli B, Piccioli D, Adamo R
Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models
Frontiers in Immunology 12 (2021)
719315
Streptococcus pyogenes
(NCBI TaxID 1314,
species name lookup)
Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Host organism: Homo sapiens
Associated disease: infection due to Streptococcus pyogenes [ICD11:
XN7YG ]
NCBI PubMed ID: 34594333Publication DOI: 10.3389/fimmu.2021.719315Journal NLM ID: 101560960Publisher: Lausanne: Frontiers Research Foundation
Correspondence: Francesca Micoli <francesca.x.micoli
gsk.com>
Institutions: GSK Vaccines Institute for Global Health (GVGH), Siena, Italy, GSK, Research Centre, Siena, Italy
Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen presentation with the immunopotentiator effect of the Toll-like receptor agonists naturally present on these systems. In this context, we are testing Generalized Modules for Membrane Antigens (GMMA), OMVs naturally released from Gram-negative bacteria mutated to increase blebbing, as carrier for polysaccharides. Here, we investigated the impact of saccharide length, density, and attachment site on the immune response elicited by GMMA in animal models, using a variety of structurally diverse polysaccharides from different pathogens (i.e., Neisseria meningitidis serogroup A and C, Haemophilus influenzae type b, and streptococcus Group A Carbohydrate and Salmonella Typhi Vi). Anti-polysaccharide immune response was not affected by the number of saccharides per GMMA particle. However, lower saccharide loading can better preserve the immunogenicity of GMMA as antigen. In contrast, saccharide length needs to be optimized for each specific antigen. Interestingly, GMMA conjugates induced strong functional immune response even when the polysaccharides were linked to sugars on GMMA. We also verified that GMMA conjugates elicit a T-dependent humoral immune response to polysaccharides that is strictly dependent on the nature of the polysaccharide. The results obtained are important to design novel glycoconjugate vaccines using GMMA as carrier and support the development of multicomponent glycoconjugate vaccines where GMMA can play the dual role of carrier and antigen. In addition, this work provides significant insights into the mechanism of action of glycoconjugates.
polysaccharide, vaccine, glycoconjugate, GMMA, carrier protein
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 7C, S. pyogenes GAC
Trivial name: GAS-PS, GAC, GAC, group A carbohydrate, GAC-PS
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823
Methods: chemical analysis, ELISA, biological assays, HPAEC-PAD, immunization, conjugation, HPLC-SEC, reductive amination, RP-UPLC
Comments, role: published polymerization frame was shifted for conformity with other records
Related record ID(s): 9698, 10909
NCBI Taxonomy refs (TaxIDs): 1314Reference(s) to other database(s): GTC:G59445KA, GlycomeDB:
37806
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Micoli F, Alfini R, Di Benedetto R, Necchi F, Schiavo F, Mancini F, Carducci M, Oldrini D, Pitirollo O, Gasperini G, Balocchi C, Bechi N, Brunelli B, Piccioli D, Adamo R
Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models
Frontiers in Immunology 12 (2021)
719315
Salmonella typhi Vi
(later renamed to: Salmonella enterica ssp. enterica sv. Typhi Vi)
(Ancestor NCBI TaxID 90370,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Salmonella typhi [ICD11:
XN4AM ];
infection due to Salmonella enterica [ICD11:
XN5VC ]
NCBI PubMed ID: 34594333Publication DOI: 10.3389/fimmu.2021.719315Journal NLM ID: 101560960Publisher: Lausanne: Frontiers Research Foundation
Correspondence: Francesca Micoli <francesca.x.micoli
gsk.com>
Institutions: GSK Vaccines Institute for Global Health (GVGH), Siena, Italy, GSK, Research Centre, Siena, Italy
Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen presentation with the immunopotentiator effect of the Toll-like receptor agonists naturally present on these systems. In this context, we are testing Generalized Modules for Membrane Antigens (GMMA), OMVs naturally released from Gram-negative bacteria mutated to increase blebbing, as carrier for polysaccharides. Here, we investigated the impact of saccharide length, density, and attachment site on the immune response elicited by GMMA in animal models, using a variety of structurally diverse polysaccharides from different pathogens (i.e., Neisseria meningitidis serogroup A and C, Haemophilus influenzae type b, and streptococcus Group A Carbohydrate and Salmonella Typhi Vi). Anti-polysaccharide immune response was not affected by the number of saccharides per GMMA particle. However, lower saccharide loading can better preserve the immunogenicity of GMMA as antigen. In contrast, saccharide length needs to be optimized for each specific antigen. Interestingly, GMMA conjugates induced strong functional immune response even when the polysaccharides were linked to sugars on GMMA. We also verified that GMMA conjugates elicit a T-dependent humoral immune response to polysaccharides that is strictly dependent on the nature of the polysaccharide. The results obtained are important to design novel glycoconjugate vaccines using GMMA as carrier and support the development of multicomponent glycoconjugate vaccines where GMMA can play the dual role of carrier and antigen. In addition, this work provides significant insights into the mechanism of action of glycoconjugates.
polysaccharide, vaccine, glycoconjugate, GMMA, carrier protein
Structure type: homopolymer
Location inside paper: Fig. 7B
Trivial name: Vi-antigen, Vi-polysaccharide
Compound class: CPS
Contained glycoepitopes: IEDB_144984,IEDB_164179,IEDB_164180,IEDB_164181
Methods: chemical analysis, ELISA, biological assays, HPAEC-PAD, immunization, conjugation, HPLC-SEC, reductive amination, RP-UPLC
Related record ID(s): 9698, 9699
NCBI Taxonomy refs (TaxIDs): 90370Reference(s) to other database(s): GTC:G67538LH, GlycomeDB:
662
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Deng JZ, Jia X, Zong C, He J, Ha S, Zhuang P
Characterization of pneumococcal serotype 7F in vaccine conjugation
Glycoconjugate Journal 40(5) (2023)
565-573
|
b-D-Galp-(1-2)-+ a-D-GlcpNAc-(1-2)-a-L-Rhap-(1-4)-+
| |
-6)-a-D-Galp-(1-3)-b-L-Rhap2Ac-(1-4)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1- |
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Streptococcus pneumoniae 7F
(Ancestor NCBI TaxID 1313,
species name lookup)
Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Associated disease: infection due to Streptococcus pneumoniae [ICD11:
XN3PW ]
NCBI PubMed ID: 37402017Publication DOI: 10.1007/s10719-023-10125-8Journal NLM ID: 8603310Publisher: Kluwer Academic Publishers
Correspondence: J.Z. Deng <james_deng
merck.com>
Institutions: Vaccine Analytical Research & Development, 770 Sumneytown Pike, P. O. Box 4, West Point, PA, WP46-3305, 19486, USA, Small Molecule Analytical Research & Development, Analytical Research & Development Merck & Co., Inc, Rahway, NJ, USA
Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20.To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. The collective information obtained by these chromatographic analysis provided insights into the pneumococcal conjugate and conjugation process.
pneumococcal conjugate vaccine, Dynamic light scattering (DLS), Multi-angle light scattering (MALS), Pneumococcal capsular polysaccharide 7F, Size-exclusion chromatography (SEC), Ultra-performance liquid chromatography (UPLC)
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 1
Trivial name: glycan epitope (glycotope)
Compound class: CPS
Contained glycoepitopes: IEDB_130648,IEDB_136044,IEDB_136105,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_137473,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_190606,IEDB_225177,IEDB_885823,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_7,SB_88
Methods: 1H NMR, SEC, conjugation, MALS, DLS, RP-UPLC, SEC-UV-MALS-DLS-RI
NCBI Taxonomy refs (TaxIDs): 1313Reference(s) to other database(s): GTC:G24963GX, GlycomeDB:
16860
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