scholarly journals Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

2020 ◽  
Vol 16 ◽  
pp. 1693-1699
Author(s):  
Sharavathi G Parameswarappa ◽  
Claney L Pereira ◽  
Peter H Seeberger
Keyword(s):  
Streptococcus Pneumoniae ◽  
Conjugate Vaccine ◽  
Virulence Factor ◽  
Capsular Polysaccharide ◽  
Acetate Group ◽  
Synthetic Strategy ◽  
Invasive Diseases ◽  
Glycoconjugate Vaccines

Streptococcus pneumoniae (SP) bacteria cause serious invasive diseases. SP bacteria are covered by a capsular polysaccharide (CPS) that is a virulence factor and the basis for SP polysaccharide and glycoconjugate vaccines. The serotype 9V is part of the currently marketed conjugate vaccine and contains an acetate modification. To better understand the importance of glycan modifications in general and acetylation in particular, defined oligosaccharide antigens are needed for serological and immunological studies. Here, we demonstrate a convergent [2 + 3] synthetic strategy to prepare the pentasaccharide repeating unit of 9V with and without an acetate group at the C-6 position of mannosamine.

A novel pneumococcal protein–polysaccharide conjugate vaccine based on biotin–streptavidin

2021 ◽  
Author(s):  
Mengze Guo ◽  
Xiaonan Guo ◽  
Chenxing Zhang ◽  
Shidong Zhu ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Lethal Dose ◽  
Public Health Problem ◽  
Protective Effects ◽  
Covalent Interaction ◽  
Pathogen Elimination ◽  
Type Iv ◽  
Wide Range

Pneumococcal disease is a serious public health problem worldwide and an important cause of morbidity and mortality among children and adults in developing countries. Although vaccination is among the most effective approaches to prevent and control pneumococcal diseases, approved vaccines have limited protective effects. We developed a pneumococcal protein–polysaccharide conjugate vaccine that is mediated by the non-covalent interaction between biotin and streptavidin. Biotinylated type IV capsular polysaccharide was incubated with a fusion protein containing core streptavidin and Streptococcus pneumoniae virulence protein and relying on the non-covalent interaction between biotin and streptavidin to prepare the protein–polysaccharide conjugate vaccine. Analysis of vaccine efficacy revealed that mice immunized with the protein–polysaccharide conjugate vaccine produced antibodies with high potency against virulence proteins and polysaccharide antigens and were able to induce Th1 and Th17 responses. The antibodies identified using an opsonophagocytic assay were capable of activating the complement system and promoting pathogen elimination by phagocytes. Additionally, mice immunized with the protein–polysaccharide conjugate vaccine and then infected with a lethal dose of Streptococcus pneumoniae demonstrated induced protective immunity. The data indicated that the pneumococcal protein–polysaccharide (biotin–streptavidin) conjugate vaccine demonstrated broad-spectrum activity applicable to a wide range of people and ease of direct coupling between protein and polysaccharide. These findings provide further evidence for the application of biotin–streptavidin in S. pneumoniae vaccines.

scholarly journals Identification of the Smallest Structure Capable of Evoking Opsonophagocytic Antibodies against Streptococcus pneumoniae Type 14

2008 ◽  
Vol 76 (10) ◽  
pp. 4615-4623 ◽  
Author(s):  
Dodi Safari ◽  
Huberta A. T. Dekker ◽  
John A. F. Joosten ◽  
Dirk Michalik ◽  
Adriana Carvalho de Souza ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antibody Response ◽  
Conjugate Vaccine ◽  
Specific Antibody ◽  
Capsular Polysaccharide ◽  
Specific Antibody Response ◽  
Specific Antibodies

ABSTRACT Synthetic overlapping oligosaccharide fragments of Streptococcus pneumoniae serotype 14 capsular polysaccharide (Pn14PS), {6)-[β-d-Galp-(1→4)-]β-d-GlcpNAc-(1→3)-β-d-Galp-(1→4)-β-d-Glcp-(1→}n, were conjugated to CRM197 protein and injected into mice to determine the smallest immunogenic structure. The resulting antibodies were then tested for Pn14PS specificity and for their capacity to promote the phagocytosis of S. pneumoniae type 14 bacteria. Earlier studies have reported that the oligosaccharide corresponding to one structural repeating unit of Pn14PS, i.e., Gal-Glc-(Gal-)GlcNAc, induces a specific antibody response to Pn14PS. The broader study described here, which evaluated 16 oligosaccharides, showed that the branched trisaccharide element Glc-(Gal-)GlcNAc is essential in inducing Pn14PS-specific antibodies and that the neighboring galactose unit at the nonreducing end contributes clearly to the immunogenicity of the epitope. Only the oligosaccharide conjugates that produce antibodies recognizing Pn14PS were capable of promoting the phagocytosis of S. pneumoniae type 14. In conclusion, the branched tetrasaccharide Gal-Glc-(Gal-)GlcNAc may be a serious candidate for a synthetic oligosaccharide conjugate vaccine against infections caused by S. pneumoniae type 14.

scholarly journals Streptococcus pneumoniae Capsular Serotype 19F Is More Resistant to C3 Deposition and Less Sensitive to Opsonophagocytosis than Serotype 6B

2008 ◽  
Vol 77 (2) ◽  
pp. 676-684 ◽  
Author(s):  
Merit Melin ◽  
Hanna Jarva ◽  
Lotta Siira ◽  
Seppo Meri ◽  
Helena Käyhty ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Conjugate Vaccine ◽  
Middle Ear ◽  
Complement Activation ◽  
Capsular Polysaccharide ◽  
Immune Defense ◽  
Pneumococcal Serotypes ◽  
Vaccine Trials ◽  
Opsonophagocytic Killing ◽  
Complement Deposition

ABSTRACT The polysaccharide capsule is a major virulence mechanism of Streptococcus pneumoniae, shielding the bacterium from phagocytes. Capsule types may differ in their abilities to resist immune defense. Antibody-mediated complement activation and opsonophagocytosis are crucial in protection against pneumococcus. Conjugate vaccine trials suggest imperfect protection against 19F. We have previously shown that significantly more anti-19F than anti-6B antibody is needed for killing in the opsonophagocytic assay (OPA). In this study, we explored whether the amount of C3 deposited on serotype 6B and 19F pneumococcal strains reflects their sensitivity to opsonophagocytosis. We compared clinical 6B and 19F nasopharyngeal, middle ear, and blood isolates as well as reference OPA strains (n = 16) for their sensitivity to opsonophagocytosis and C3 deposition. Sixfold anticapsular antibody concentrations were required for 50% opsonophagocytic killing of 19F compared to that of 6B strains. Serotype 19F was more resistant to C3 deposition than 6B. Complement deposition and opsonophagocytosis were dependent on the concentration of anticapsular antibodies. Differences between pneumococcal serotypes in antibody-mediated protection may partly be explained by the abilities of the capsules to resist complement deposition. These findings support previous studies suggesting that higher antibody concentrations to the capsular polysaccharide are needed for protection against disease caused by serotype 19F than that caused by 6B.

scholarly journals Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

2013 ◽  
Vol 20 (6) ◽  
pp. 858-866 ◽  
Author(s):  
Catia T. Perciani ◽  
Giovana C. Barazzone ◽  
Cibelly Goulart ◽  
Eneas Carvalho ◽  
Joaquin Cabrera-Crespo ◽  
...  
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Conjugate Vaccine ◽  
Reductive Amination ◽  
Capsular Polysaccharide ◽  
Protective Antigen ◽  
Protein A ◽  
Surface Protein ◽  
Promising Alternative ◽  
Pneumococcal Surface Protein A

ABSTRACTDespite the substantial beneficial effects of incorporating the 7-valent pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype replacement has been observed after its widespread use. As there are many serotypes currently documented, the use of a conjugate vaccine relying on protective pneumococcal proteins as active carriers is a promising alternative to expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B) and recombinant pneumococcal surface protein A (rPspA), a well-known protective antigen fromStreptococcus pneumoniae, were covalently attached by two conjugation methods. The conjugation methodology developed by our laboratory, employing 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an activating agent through carboxamide formation, was compared with reductive amination, a classical methodology. DMT-MM-mediated conjugation was shown to be more efficient in coupling PS6B to rPspA clade 1 (rPspA1): 55.0% of PS6B was in the conjugate fraction, whereas 24% was observed in the conjugate fraction with reductive amination. The influence of the conjugation process on the rPspA1 structure was assessed by circular dichroism. According to our results, both conjugation processes reduced the alpha-helical content of rPspA; reduction was more pronounced when the reaction between the polysaccharide capsule and rPspA1 was promoted between the carboxyl groups than the amine groups (46% and 13%, respectively). Regarding the immune response, both conjugates induced functional anti-rPspA1 and anti-PS6B antibodies. These results suggest that the secondary structure of PspA1, as well as its reactive groups (amine or carboxyl) involved in the linkage to PS6B, may not play an important role in eliciting a protective immune response to the antigens.

Serotype coverage of pneumococcal conjugate vaccine and drug susceptibility of Streptococcus pneumoniae isolated from invasive or non-invasive diseases in central Thailand, 2006–2009

Vaccine ◽  
2010 ◽  
Vol 28 (19) ◽  
pp. 3440-3444 ◽  
Author(s):  
Somporn Srifeungfung ◽  
Chanwit Tribuddharat ◽  
Sopita Comerungsee ◽  
Tanittha Chatsuwan ◽  
Vipa Treerauthanaweeraphong ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Drug Susceptibility ◽  
Non Invasive ◽  
Invasive Diseases ◽  
Central Thailand
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