Development of approaches to a third-generation carbohydrate-conjugate vaccine against<i>Streptococcus pneumoniae</i>: the search for optimal oligosaccharide ligands

Gening, Marina L.; Курбатова, Е. А.; Tsvetkov, Yury E.; Nifantiev, Nikolay E.

doi:10.1070/rcr4574

Cited by 38 publications

(28 citation statements)

References 95 publications

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“…These studies revealed that conjugated short saccharide chains starting from di‐ to pentasaccharides (Figure ) that are equivalent or less than one or two RU derived from the CPS of S. pneumoniae serotypes 3, 6A, 6B, 14, 17S, 23F were able to provoke protective immune response in mice and rabbits and could be used as potential candidates to design specific glycoconjugate vaccines . A number of studies revealed that two epitopes, (1→3)‐ and (1→4)‐linked rhamnosyl‐ribitol, were the crucial epitopes (Figure b) and need to be included in oligosaccharide design to generate an effective glycoconjugate vaccine against the serotypes 6A, 6B, 6C and 6D . To identify the minimum epitope of S. pneumoniae serotype 14, sixteen structurally different saccharide fragments ranging from tri‐ to dodecasaccharides were synthesised and conjugated individually with the CRM 197 carrier protein by using a diethyl squarate linker.…”

Section: Application and Impact Of Variables In Antibacterial Glycocsupporting

confidence: 65%

“…In addition to the semisynthetic vaccines, various synthetic approaches have been used to identify the effective immunogenic saccharide epitopes of the different pneumococcal serotypes to develop the third generation glycoconjugate vaccines . These studies revealed that conjugated short saccharide chains starting from di‐ to pentasaccharides (Figure ) that are equivalent or less than one or two RU derived from the CPS of S. pneumoniae serotypes 3, 6A, 6B, 14, 17S, 23F were able to provoke protective immune response in mice and rabbits and could be used as potential candidates to design specific glycoconjugate vaccines .…”

Section: Application and Impact Of Variables In Antibacterial Glycocmentioning

confidence: 99%

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An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity

Khatun

Stephenson

Tóth

2017

Chemistry A European J

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Bacterial cell-surface-derived or mimicked carbohydrate moieties that act as protective antigens are used in the development of antibacterial glycoconjugate vaccines. The carbohydrate antigen must have a minimum length or size to maintain the conformational structure of the antigenic epitope(s). The presence or absence of O-acetate, phosphate, glycerol phosphate and pyruvate ketal plays a vital role in defining the immunogenicity of the carbohydrate antigen. The nature of the carrier protein, spacer and conjugation pattern used to develop the glycoconjugate vaccine also defines its overall spatial orientation which in turn affects its avidity and selectivity of interaction with the desired target(s). In addition, the ratio of carbohydrate to protein in glycoconjugate vaccines also makes an important contribution in determining the optimum immunological response. This Review article presents the importance of these variables in the development of antibacterial glycoconjugate vaccines and their effects on immune efficacy.

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Section: Application and Impact Of Variables In Antibacterial Glycocsupporting

confidence: 65%

Section: Application and Impact Of Variables In Antibacterial Glycocmentioning

confidence: 99%

An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity

Khatun

Stephenson

Tóth

2017

Chemistry A European J

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“…A promising direction is the development of carbohydrate pneumococcal vaccines of the third-generation based on synthetic oligosaccharides (OSs) related to the structurally defined regions of CP coupled to protein carriers (13). …”

Section: Introductionmentioning

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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“…Вариабельность бактериального КП S. pneu moniae серотипа 3 может оказывать влияние на качество вакцинных препаратов. Для устранения этого недостатка перспективным является использование протективных синтетических олигосахаридов строго определенного химического строения, являющихся аналогами КП S. pneumoniae серотипа 3, конъюгированных с белком-носителем для индукции Т-зависимого иммунного ответа и иммунологической памяти [52][53][54][55]. Для конструирования мультивалентной пневмококковой вакцины можно использовать конъюгированные синтетические олигосахариды или их комбинацию с бактериальными КП [56].…”

Section: экспериментальные исследованияunclassified

Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines

Zaitsev¹,

Курбатова²,

Egorova³

et al. 2020

Journal of microbiology, epidemiology and immunobiology

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The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.

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Development of approaches to a third-generation carbohydrate-conjugate vaccine againstStreptococcus pneumoniae: the search for optimal oligosaccharide ligands

Cited by 38 publications

References 95 publications

An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity

An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity

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

Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines

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