O-acetylation of typhoid capsular polysaccharide confers polysaccharide rigidity and immunodominance by masking additional epitopes

Hitri, Krisztina; Kuttel, Michelle M.; Benedetto, Gianluigi De; Lockyer, Kay; Gao, Fang; Hansal, Peter; Rudd, Timothy R.; Beamish, Emma; Rijpkema, Sjoerd; Ravenscroft, Neil; Bolgiano, Barbara

doi:10.1016/j.vaccine.2019.05.050

Cited by 25 publications

(22 citation statements)

References 40 publications

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“…For Vi PS, O -acetylation is a major factor for immune potency (Szu et al 1991 ; Hitri et al 2019 ). Vi PS is variably O -acetylated at the carbon 3 of the repeating monosaccharide.…”

Section: Part IImentioning

confidence: 99%

“…Vi PS is variably O -acetylated at the carbon 3 of the repeating monosaccharide. The O -acetyl groups are the most solvent exposed (Szu et al 1991 ; Hitri et al 2019 ) and the primary epitope exposed for antibody binding since carboxyl and N -acetyl groups are buried within the PS helix, making them less available as antibody targets, which are only be exposed in de- O -acetylated Vi (Hitri et al 2019 ). Antibodies reacting with carboxyl and/or N -acetyl groups in de- O -acetylated Vi have been reported, but these groups are unlikely to be dominant in Vi vaccines, which meet the recommended level of O -acetylation (Qadri et al 1990 ; Szu et al 1991 ).…”

Section: Part IImentioning

confidence: 99%

“…Antibodies reacting with carboxyl and/or N -acetyl groups in de- O -acetylated Vi have been reported, but these groups are unlikely to be dominant in Vi vaccines, which meet the recommended level of O -acetylation (Qadri et al 1990 ; Szu et al 1991 ). The relatively high viscosity of Vi makes it more challenging to characterise with physicochemical methods like HPLC-SEC or matrix-based sample separation methods, for example ultrafiltration membranes or solid-phase extraction cartridges in a free polysaccharide assay (Hitri et al 2019 ). Partially, O -acetylated PS may be structurally beneficial in a formulation to give access to additional epitope(s) (Hitri et al 2019 ).…”

Section: Part IImentioning

confidence: 99%

“…The relatively high viscosity of Vi makes it more challenging to characterise with physicochemical methods like HPLC-SEC or matrix-based sample separation methods, for example ultrafiltration membranes or solid-phase extraction cartridges in a free polysaccharide assay (Hitri et al 2019 ). Partially, O -acetylated PS may be structurally beneficial in a formulation to give access to additional epitope(s) (Hitri et al 2019 ). Nevertheless, the key to an effective Vi vaccine is to ensure that the O -acetyl content will be at least 52% or 2.0 mmol/g of PS as specified by WHO recommendations (Szu et al 1991 ; Lemercinier et al 2000 ; WHO 2014b ).…”

Section: Part IImentioning

confidence: 99%

“…However, due to the importance of the O -acetyl pattern for vaccine immunogenicity, complementary methods to colorimetry and immunoassays were developed, enabling acetyl group detection, content and positioning on the purified CPSs. These are currently NMR, and HPAEC with conductivity detection (HPAEC-CD), although this is not yet widely used (Lemercinier et al 2000 ; Kao and Tsai 2004 ; Hitri et al 2019 ). NMR is considered to give more information on O -acetyl position in general and has benefits over wet chemical methods since it can be used for CPS fingerprinting and gives a wider spectrum of information; however, it becomes difficult to interpret when more complex cross-linked conjugates are evaluated.…”

Section: Part IImentioning

confidence: 99%

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Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

et al. 2021

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The global spread of enteric disease, the increasingly limited options for antimicrobial treatment and the need for effective eradication programs have resulted in an increased demand for glycoconjugate enteric vaccines, made with carbohydrate-based membrane components of the pathogen, and their precise characterisation. A set of physico-chemical and immunological tests are employed for complete vaccine characterisation and to ensure their consistency, potency, safety and stability, following the relevant World Health Organization and Pharmacopoeia guidelines. Variable requirements for analytical methods are linked to conjugate structure, carrier protein nature and size and O-acetyl content of polysaccharide. We investigated a key stability-indicating method which measures the percent free saccharide of Salmonella enterica subspecies enterica serovar Typhi capsular polysaccharide, by detergent precipitation, depolymerisation and HPAEC-PAD quantitation. Together with modern computational approaches, a more precise design of glycoconjugates is possible, allowing for improvements in solubility, structural conformation and stability, and immunogenicity of antigens, which may be applicable to a broad spectrum of vaccines. More validation experiments are required to establish the most effective and suitable methods for glycoconjugate analysis to bring uniformity to the existing protocols, although the need for product-specific approaches will apply, especially for the more complex vaccines. An overview of current and emerging analytical approaches for the characterisation of vaccines against Salmonella Typhi and Shigella species is described in this paper. This study should aid the development and licensing of new glycoconjugate vaccines aimed at the prevention of enteric diseases.

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“…For Vi PS, O -acetylation is a major factor for immune potency (Szu et al 1991 ; Hitri et al 2019 ). Vi PS is variably O -acetylated at the carbon 3 of the repeating monosaccharide.…”

Section: Part IImentioning

confidence: 99%

Section: Part IImentioning

confidence: 99%

Section: Part IImentioning

confidence: 99%

Section: Part IImentioning

confidence: 99%

Section: Part IImentioning

confidence: 99%

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Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

et al. 2021

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Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity

Ojha

Prajapati

2021

Journal Cellular Physiology

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Vaccination is a significant advancement or preventative strategy for controlling the spread of various severe infectious and noninfectious diseases. The purpose of vaccination is to stimulate or activate the immune system by injecting antigens, i.e., either whole microorganisms or using the pathogen's antigenic part or macromolecules. Over time, researchers have made tremendous efforts to reduce vaccine side effects or failure by developing different strategies combining with immunoinformatic and molecular biology. These newly designed vaccines are composed of single or several antigenic molecules derived from a pathogenic organism. Although, whole‐cell vaccines are still in use against various diseases but due to their ineffectiveness, other vaccines like DNA‐based, RNA‐based, and protein‐based vaccines, with the addition of immunostimulatory agents, are in the limelight. Despite this, many researchers escape the most common fundamental phenomenon of protein posttranslational modifications during the development of vaccines, which regulates protein functional behavior, evokes immunogenicity and stability, etc. The negligence about post translational modification (PTM) during vaccine development may affect the vaccine's efficacy and immune responses. Therefore, it becomes imperative to consider these modifications of macromolecules before finalizing the antigenic vaccine construct. Here, we have discussed different types of posttranslational/transcriptional modifications that are usually considered during vaccine construct designing: Glycosylation, Acetylation, Sulfation, Methylation, Amidation, SUMOylation, Ubiquitylation, Lipidation, Formylation, and Phosphorylation. Based on the available research information, we firmly believe that considering these modifications will generate a potential and highly immunogenic antigenic molecule against communicable and noncommunicable diseases compared to the unmodified macromolecules.

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Structure, Classification and Modification of Polysaccharides

Guo

Liu

Cui

2021

Comprehensive Glycoscience

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O-acetylation of typhoid capsular polysaccharide confers polysaccharide rigidity and immunodominance by masking additional epitopes

Cited by 25 publications

References 40 publications

Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity

Structure, Classification and Modification of Polysaccharides

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