Conjugates of Group A and W135 Capsular Polysaccharides of<i>Neisseria meningitidis</i>Bound to Recombinant<i>Staphylococcus aureus</i>Enterotoxin C1: Preparation, Physicochemical Characterization, and Immunological Properties in Mice

Zhang, Jin; Bohach, Gregory A.; Shiloach, Joseph; Norris, Scott E.; Freedberg, Darón I.; Deobald, Claudia F.; Coxon, Bruce; Robbins, John B.; Schneerson, Rachel

doi:10.1128/iai.73.12.7887-7893.2005

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…Although the natural occurrence of both O-acetylated and non-O-acetylated W and Y isolates has been demonstrated (i.e., in the UK with a predominance of non-O-acetylated W and O-acetylated Y strains [ 23 ], and during the Hajj outbreak where all the W strains were non-O-acetylated [ 24 ]), the currently licensed serogroup W and Y conjugate vaccines contain the O-acetylated CPS. The general role of O-acetylation of these CPSs is still debated, however several studies conducted in the preclinical stage and using human sera seem to confirm that there is no difference in functional activity of O-acetylated or non-O-acetylated CPSs [ 22 , 25 , 26 , 27 ]. By investigating the meningococcal Y antigen, Fusco et al [ 22 ] suggested that the O-acetyl groups may mask an important epitope to the immune system and thereby mislead the antibody response, resulting in an escape mechanism.…”

Section: O-acetylation In Conjugate Vaccinesmentioning

confidence: 99%

Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines

Berti

Ricco²,

Rappuoli

2018

Molecules

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The incidence of infectious diseases caused by several bacterial pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis, has been dramatically reduced over the last 25 years through the use of glycoconjugate vaccines. The structures of the bacterial capsular polysaccharide (CPS) antigens, extracted and purified from microbial cultures and obtained with very high purity, show that many of them are decorated by O-acetyl groups. While these groups are often considered important for the structural identity of the polysaccharides, they play a major role in the functional immune response to some vaccines such as meningococcal serogroup A and Salmonella typhi Vi, but do not seem to be important for many others, such as meningococcal serogroups C, W, Y, and type III Group B Streptococcus. This review discusses the O-acetylation status of CPSs and its role in the immunological responses of these antigens.

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Section: O-acetylation In Conjugate Vaccinesmentioning

confidence: 99%

Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines

Berti

Ricco²,

Rappuoli

2018

Molecules

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“…However, Vi is not suitable for routine immunization of infants and young children because of its age-related immunogenicity and T-cell independence. As was shown for other capsular polysaccharides, such as Haemophilus influenzae type b (8,37); meningococcus groups A, C, and W135; and Streptococcus pneumoniae (12,20), Vi covalently bound with protein conferred T-cell dependence and increased immunogenicity (48)(49)(50). To date, diphtheria toxoid (DT), tetanus toxoid (TT), cholera toxins (CT), the B subunit of the heat-labile toxin (LT-B) of Escherichia coli, recombinant outer membrane protein of Klebsiella pneumoniae (rP40), and iron-regulated outer-membrane proteins (IROMPs) of S. Typhi have served as carriers for Vi polysaccharide in laboratory studies (16, 17, 32, 48-50; personal communications).…”

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confidence: 99%

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Cui

Carbis

et al. 2010

Clin Vaccine Immunol

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Typhoid fever remains a serious public health problem in developing countries, especially among young children. Recent studies showed more than 50% of typhoid cases are in children under 5 years old. Licensed vaccines, such as Salmonella enterica serovar Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conjugate, prepared by binding Vi to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), induces protective levels of antibody at as young as 2 years old. Because of the lack of regulatory precedent for rEPA in licensing vaccines, we employed diphtheria toxoid (DT) as the carrier protein to accommodate accessibility in developing countries. Five lots of Vi-DT conjugates were prepared using adipic acid dihydrazide (ADH) as the linker. All 5 lots showed consistency in their physical and chemical characteristics and final yields. These Vi-DT conjugates elicited levels of IgG anti-Vi in young mice significantly higher than those in mice injected with Vi alone and induced a booster response upon reinjection. This booster effect was absent if the Vi replaced one of the two conjugate injections. Vi-DT was stable under repeated freeze-thaw (20 cycles). We plan to perform clinical evaluation of the safety and immunogenicity of Vi-DT when added to the infant combination vaccines.Typhoid fever, a serious systemic infection caused by Salmonella enterica serovar Typhi, remains a major public health problem in Central Asia, Southeast Asia, Africa, and Latin America (11,52,53). It was estimated that more than 21 million cases of typhoid fever and Ͼ200,000 deaths occurred in 2000 (10). The treatment of patients and management of asymptomatic carriers are becoming more difficult due to the worldwide emergence of multidrug-resistant (MDR) strains (2,15,29,42,43). Vaccination is considered the most promising strategy for the control of typhoid fever in developing countries (11,19,52,53).Typhoid fever in children younger than 5 years old has often been unrecognized due to atypical clinical symptoms, difficulties in the number and volume of blood drawings, and use of less than optimal culture media (35,46). Several studies have shown that the incidence of typhoid fever among children less than 5 years old is similar to that in school age children and young adults (14,27,34,50,51).The 3 licensed typhoid vaccines have limited efficacy, and none are suitable for young children under 5 years old. The use of heat-inactivated whole-cell vaccine was suspended in many countries because of its reactogenicity. The parenteral Vi polysaccharide and the live attenuated oral Ty21a vaccine were introduced in the late 1980s; both vaccines are well accepted and confer moderate protection (50 to 70%) in older children and adults. However, neither vaccine is licensed for routine immunization of infants (52).The Vi capsular polysaccharide is both an essential virulence factor and a protective antigen for S. Typhi (36,38,39). The concentration of serum IgG anti-Vi is correlated with immunity to the pathogen (22...

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“…However, their data indicate that for some sera the agreement in anti-OAc+ vs. anti OAc- W IgG assignments was serum-specific and did not reflect the in vitro functional (killing) activity. Jin et al 68 analyzed the immunogenicity of MenW polysaccharide conjugated to Staphylococcus enterotoxin C1 having low levels of O-acetylation in mice; removal of these O-acetyl moieties had no adverse effect on the observed immunogenicity.…”

Section: Polysaccharidesmentioning

confidence: 99%

Factors contributing to the immunogenicity of meningococcal conjugate vaccines

Bröker¹,

Costantino

2016

Human Vaccines & Immunotherapeutics

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Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines.One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics.

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Conjugates of Group A and W135 Capsular Polysaccharides ofNeisseria meningitidisBound to RecombinantStaphylococcus aureusEnterotoxin C1: Preparation, Physicochemical Characterization, and Immunological Properties in Mice

Cited by 7 publications

References 32 publications

Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines

Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Factors contributing to the immunogenicity of meningococcal conjugate vaccines

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