The use of biotinylated oligosaccharides related to fragments of capsular polysaccharides from Streptococcus pneumoniae serotypes 3 and 14 as a tool for assessment of the level of vaccine-induced antibody response to neoglycoconjugates

Курбатова, Е. А.; Akhmatova, Elina; Ахматова, Н. К.; Egorova, N B; Yastrebova, N. E.; Romanenko, E E; Leonova, A. Yu.; Поддубиков, А. В.; Tsvetkov, Yury E.; Сухова, Е. В.; Gening, Marina L.; Yashunsky, Dmitry V.; Nifantiev, Nikolay E.

doi:10.1007/s11172-016-1488-7

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…Abs to the short-length OSs may have less opportunity to recognize chemically treated CP, as treatment may hide antigenic determinants; antigenic determinants may be more accessible to Abs generated against OSs with longer carbohydrate chains. However, we showed in a previous study that tetra-BSA conjugate-induced Abs more actively agglutinated live S. pneumoniae type 14 cells than did hexa-BSA - and octa-BSA -induced Abs; their activity equaled that of commercial serotype-specific rabbit pneumococcal antisera ( 35 ).…”

Section: Discussionmentioning

confidence: 67%

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: Discussionmentioning

confidence: 67%

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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“…No differences in opsonophagocytic activity determined by flow-cytometry assay were observed between the glycoconjugates; only sera to the tetra-BSA conjugate caused greater phagocytosis of bacteria than Abs in sera to Prevenar-13, which includes CRM 197 -conjugated CP of S. pneumoniae type 3 as a component. The highest capacity of tetrasaccharide-BSA Ab to bind live bacteria of S. pneumoniae type 3 was observed in our previous study using the slide agglutination test (70).…”

Section: Discussionmentioning

confidence: 68%

“…Synthetic OSs (35) were conjugated to bovine serum albumin (BSA) (Sigma-Aldrich, St. Louis, MO, USA) and biotin as previously described (36,37). The structures and designations are illustrated in Figure 1.…”

Section: Synthetic Oligosaccharides and Their Conjugatesmentioning

confidence: 99%

“…BSA has been frequently used as a protein carrier in engineered immunogenic glycoconjugates and other types of biomolecular systems (39). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry data previously demonstrated that the di-, tri-, and tetra-BSA conjugates contained on average 19, 18, and 16 oligosaccharide ligands per protein molecule, corresponding with 9, 13, and 15% carbohydrate content by weight, respectively (35,36). Lyophilized oligosaccharidebiotin and oligosaccharide-BSA conjugates are stable at +4°C without any decrease of activity within at least 3 years (observation period).…”

Section: Synthetic Oligosaccharides and Their Conjugatesmentioning

confidence: 99%

“…Biotinylated di-, tri-and tetrasaccharide related to S. pneumoniae type 3 (35) served as a positive control. Structurally unrelated biotinylated tetrasaccharide of S. pneumoniae type 14 (36,44) and hexasaccharide fragments of galactans I and II of the O-antigen of Klebsiella pneumoniae ( Figure 2) (45-47) were used as a negative control. The biotinylated oligosaccharides were immobilized on the surface of streptavidin pre-coated plates and sera to di-, tri-, and tetra-BSA conjugates were added.…”

Section: Measurement Of Antibody Response To Oligosaccharides and Capmentioning

confidence: 99%

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Higher Cytokine and Opsonizing Antibody Production Induced by Bovine Serum Albumin (BSA)-Conjugated Tetrasaccharide Related to Streptococcus pneumoniae Type 3 Capsular Polysaccharide

et al. 2020

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A number of studies have demonstrated the limited efficacy of S. pneumoniae type 3 capsular polysaccharide (CP) in the 13-valent pneumococcal conjugate vaccine against serotype 3 invasive pneumococcal diseases and carriage. Synthetic oligosaccharides (OSs) may provide an alternative to CPs for development of novel conjugated pneumococcal vaccines and diagnostic test systems. A comparative immunological study of di–, tri–, and tetra–bovine serum albumin (BSA) conjugates was performed. All oligosaccharides conjugated with biotin and immobilized on streptavidin-coated plates stimulated production of IL-1α, IL-2, IL-4, IL-5, IL-10, IFNγ, IL-17A, and TNFα, but not IL-6 and GM-CSF in monocultured mice splenocytes. The tetrasaccharide–biotin conjugate stimulated the highest levels of IL-4, IL-5, IL-10, and IFNγ, which regulate expression of specific immunoglobulin isotypes. The tetra–BSA conjugate adjuvanted with aluminum hydroxide elicited high levels of IgM, IgG1, IgG2a, and IgG2b antibodies (Abs). Anti-CP-induced Abs could only be measured using the biotinylated tetrasaccharide. The tetrasaccharide ligand possessed the highest binding capacity for anti-OS and antibacterial IgG Abs in immune sera. Sera to the tetra–BSA conjugate promoted greater phagocytosis of bacteria by neutrophils and monocytes than the CRM197-CP-antisera. Sera of mice immunized with the tetra–BSA conjugate exhibited the highest titer of anti-CP IgG1 Abs compared with sera of mice inoculated with the same doses of di– and tri–BSA conjugates. Upon intraperitoneal challenge with lethal doses of S. pneumoniae type 3, the tri– and tetra–BSA conjugates protected mice more significantly than the di–BSA conjugate. Therefore, it may be concluded that the tetrasaccharide ligand is an optimal candidate for development of a semi-synthetic vaccine against S. pneumoniae type 3 and diagnostic test systems.

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Estimation of the degree of conjugation of oligosaccharide haptens to bovine serum albumin in the course of the squarate procedure using gel permeation HPLC

et al. 2016

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The use of biotinylated oligosaccharides related to fragments of capsular polysaccharides from Streptococcus pneumoniae serotypes 3 and 14 as a tool for assessment of the level of vaccine-induced antibody response to neoglycoconjugates

Cited by 11 publications

References 17 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

Higher Cytokine and Opsonizing Antibody Production Induced by Bovine Serum Albumin (BSA)-Conjugated Tetrasaccharide Related to Streptococcus pneumoniae Type 3 Capsular Polysaccharide

Estimation of the degree of conjugation of oligosaccharide haptens to bovine serum albumin in the course of the squarate procedure using gel permeation HPLC

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