Development of approaches to creation of experimental test system for evaluation of antigenic activity of synthetic oligosaccharide ligands related to fragments of the Streptococcus pneumoniae type 14 capsular polysaccharide

Курбатова, Е. А.; Vorobiov, D. S.; Семенова, И. Б.; Сухова, Е. В.; Yashunsky, Dmitry V.; Tsvetkov, Yury E.; Nifantiev, Nikolay E.

doi:10.1134/s0006297913070122

Cited by 11 publications

(4 citation statements)

References 16 publications

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“…Ab titers were measured by enzyme-linked immunosorbent assay (ELISA) from individual blood samples of 6–12 mice/dose (the results of two experiments), or from pooled sera of 6 mice/conjugate, as previously described (27). To prepare for the titer assays, flat-bottom plates (Biomedicals, Russia) were coated with S. pneumoniae type 14 bacterial CP (1 µg/well) or synthetic CP (0.5 µg/well).…”

Section: Methodsmentioning

confidence: 99%

Neoglycoconjugate of Tetrasaccharide Representing One Repeating Unit of the Streptococcus pneumoniae Type 14 Capsular Polysaccharide Induces the Production of Opsonizing IgG1 Antibodies and Possesses the Highest Protective Activity As Compared to Hexa- and Octasaccharide Conjugates

et al. 2017

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Identifying protective synthetic oligosaccharide (OS) epitopes of Streptococcus pneumoniae capsular polysaccharides (CPs) is an indispensable step in the development of third-generation carbohydrate pneumococcal vaccines. Synthetic tetra-, hexa-, and octasaccharide structurally related to CP of S. pneumoniae type 14 were coupled to bovine serum albumin (BSA), adjuvanted with aluminum hydroxide, and tested for their immunogenicity in mice upon intraperitoneal prime-boost immunizations. Injections of the conjugates induced production of opsonizing anti-OS IgG1 antibodies (Abs). Immunization with the tetra- and octasaccharide conjugates stimulated the highest titers of the specific Abs. Further, the tetrasaccharide ligand demonstrated the highest ability to bind OS and CP Abs. Murine immune sera developed against tetra- and octasaccharide conjugates promoted pathogen opsonization to a higher degree than antisera against conjugated hexasaccharide. For the first time, the protective activities of these glycoconjugates were demonstrated in mouse model of generalized pneumococcal infections. The tetrasaccharide conjugate possessed the highest protective activities. Conversely, the octasaccharide conjugate had lower protective activities and the lowest one showed the hexasaccharide conjugate. Sera against all of the glycoconjugates passively protected naive mice from pneumococcal infections. Given that the BSA-tetrasaccharide induced the most abundant yield of specific Abs and the best protective activity, this OS may be regarded as the most promising candidate for the development of conjugated vaccines against S. pneumoniae type 14 infections.

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Section: Methodsmentioning

confidence: 99%

Neoglycoconjugate of Tetrasaccharide Representing One Repeating Unit of the Streptococcus pneumoniae Type 14 Capsular Polysaccharide Induces the Production of Opsonizing IgG1 Antibodies and Possesses the Highest Protective Activity As Compared to Hexa- and Octasaccharide Conjugates

et al. 2017

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“…The HS conjugate [β-Gal-(1 → 4)-β-Glc-(1 → 6)-[β-Gal-(1 → 4)]-β-GlcNAc-(1 → 3)-β-Gal-(1 → 4)-β-Glc-O-spacer] 15 -BSA was prepared by the squarate method and contained, according to MALDI-TOF data, on average, 15 HS residues as previously described ( 30 , 31 ) and 19% carbohydrates on a dry weight basis (Figure 1 ). The BSA is often used as a protein carrier to design immunogenic GCs and biomolecular systems ( 32 ) of other types.…”

Section: Methodsmentioning

confidence: 99%

“…A booster immunization of GC + AL was carried out on d 92. Anti-PS IgG and subisotype (IgG1, IgG2a, IgG2b, IgG3) levels were determined by the enzyme-linked immunosorbent assay (ELISA) as previously described ( 30 ). Specifically, flat-bottom plates (Biochemicals, Russia) were coated with a PS preparation from S. pneumoniae type 14 (1 μg/well).…”

Section: Methodsmentioning

confidence: 99%

The Effect of a BSA Conjugate of a Synthetic Hexasaccharide Related to the Fragment of Capsular Polysaccharide of Streptococcus pneumoniae Type 14 on the Activation of Innate and Adaptive Immune Responses

et al. 2016

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We report the effect of a bovine serum albumin (BSA) conjugate of a synthetic hexasaccharide (HS) related to the fragment of the capsular polysaccharide (PS) of Streptococcus pneumoniae type 14 on the stimulation of innate immune system and the subsequent development of a PS-specific antibody response. Glycoconjugate (GC) in the presence (GC + AL) or absence of aluminum hydroxide was administered to mice twice. GC increased the number of TLR2-expressing cells and induced the maturation of dendritic cells (CD11c+, CD80+ and, MHCII+), which secreted IL-1β, IL-6, and TNFα into the culture medium. The level of IL-1β, IL-10, IFNγ, and TNFα in the blood increased within 24 h after the single GC administration to mice. On day 7, the numbers of splenic CD4+ and CD8+ T lymphocytes and B lymphocytes increased. After the second immunization, the levels of CD4+ and CD8+ T lymphocytes were lower than in the control, whereas the B cell, NK cell, and MHC class II-expressing cell numbers remained enhanced. However, of the presence of anti-PS, IgG antibodies were not detected. The addition of aluminum hydroxide to GC stimulated the production of GM-CSF, IL-1β, IL-5, IL-6, IL-10, IL-17, IFNγ, and TNFα. Anti-PS IgG1 antibody titers 7 days after the second immunization were high. During that period, normal levels of splenic CD4+ T lymphocytes were maintained, whereas reduced CD8+ T lymphocyte numbers and increased levels of B lymphocytes, NK cells, and MHC class II-expressing cell numbers were observed. Anti-PS IgG levels diminished until day 92. A booster immunization with GC + AL stimulated the production of anti-PS IgG memory antibodies, which were determined within 97 days. The elucidation of specific features of the effect of the synthetic HS conjugate on the stimulation of innate, cell-mediated immunity, and antibody response can favor the optimization of GC vaccine design.

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“…In the framework of our research program aiming at the design of carbohydrate pneumococcal vaccines based on synthetic oligosaccharide ligands structurally related to the CPs, we synthesized a set of oligosaccharides representing fragments of the CPs of serotypes 3 and 14 ( Sukhova et al, 2014 ; Tsvetkov et al, 2017 ) and investigated their immunological properties ( Kurbatova et al, 2013 ; Akhmatova et al, 2016 ; Kurbatova et al, 2016 ; Kurbatova et al, 2017 ; Kurbatova et al, 2020 ). Recently, we published the synthesis of spacer-armed pseudotetrasaccharide 1 corresponding to a repeating unit of the S. pneumoniae type 6B polysaccharide ( Sukhova et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Preliminary Immunological Evaluation of a Pseudotetrasaccharide Related to a Repeating Unit of the Streptococcus pneumoniae Serotype 6A Capsular Polysaccharide

Сухова

Yashunsky

Курбатова

et al. 2021

Front. Mol. Biosci.

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2-Aminoethyl glycoside of the pseudotetrasaccharide α-d-Glcp-(1→3)-α-l-Rhap-(1→3)-d-Rib-ol-(5-P-2)-α-d-Galp corresponding to a repeating unit of the Streptococcus pneumoniae type 6A capsular polysaccharide has been synthesized. A suitably protected pseudotrisaccharide α-d-Glcp-(1→3)-α-l-Rhap-(1→3)-d-Rib-ol with a free 5-OH group in the ribitol moiety and a 2-OH derivative of 2-trifluoroacetamidoethyl α-d-galactopyranoside have been efficiently prepared and then connected via a phosphate bridge using the hydrogen phosphonate procedure. Preliminary immunological evaluation of this pseudotetrasaccharide and the previously synthesized pseudotetrasaccharide corresponding to a repeating unit of the capsular polysaccharide of S. pneumoniae serotype 6B has shown that they contain epitopes specifically recognized by anti-serogroup 6 antibodies and are able to model well the corresponding capsular polysaccharides. Conjugates of the synthetic pseudotetrasaccharides with bovine serum albumin were shown to be immunogenic in mice.

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Development of approaches to creation of experimental test system for evaluation of antigenic activity of synthetic oligosaccharide ligands related to fragments of the Streptococcus pneumoniae type 14 capsular polysaccharide

Cited by 11 publications

References 16 publications

Neoglycoconjugate of Tetrasaccharide Representing One Repeating Unit of the Streptococcus pneumoniae Type 14 Capsular Polysaccharide Induces the Production of Opsonizing IgG1 Antibodies and Possesses the Highest Protective Activity As Compared to Hexa- and Octasaccharide Conjugates

Neoglycoconjugate of Tetrasaccharide Representing One Repeating Unit of the Streptococcus pneumoniae Type 14 Capsular Polysaccharide Induces the Production of Opsonizing IgG1 Antibodies and Possesses the Highest Protective Activity As Compared to Hexa- and Octasaccharide Conjugates

The Effect of a BSA Conjugate of a Synthetic Hexasaccharide Related to the Fragment of Capsular Polysaccharide of Streptococcus pneumoniae Type 14 on the Activation of Innate and Adaptive Immune Responses

Synthesis and Preliminary Immunological Evaluation of a Pseudotetrasaccharide Related to a Repeating Unit of the Streptococcus pneumoniae Serotype 6A Capsular Polysaccharide

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