Evaluation of impact of temperature and pH alterations on the size and antigenicity of meningococcal serogroup A and X polysaccharides and conjugates

Sharma, Nitya; Hanif, Sarmad; Rana, Rakesh; Upadhyay, Dilip J.; Chhikara, Manoj Kumar

doi:10.1016/j.vaccine.2018.12.051

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…The faster kinetic of hydrolysis of MenA polysaccharide compared to other antigens is well established 19 . A recent report suggests that a MenA-TT glycoconjugate is more stable to pH and temperature variation compared to the unconjugated polysaccharide, but this work only evaluated the activity of the conjugate in terms of antigenicity and not immunogenicity, and the effect of (partial) degradation on human immunization is unpredictable 21 . Generally, stability issues can be controlled by storage at 2-8°C or overcome by freeze-drying.…”

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confidence: 99%

A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

Enotarpi

Tontini²,

Balocchi³

et al. 2020

Nat Commun

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Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) consists of (1 → 6)-2-acetamido-2-deoxy-α-D-mannopyranosyl phosphate repeating units, O-acetylated at position C3 or C4. Glycomimetics appear attractive to overcome the CPS intrinsic lability in physiological media, due to cleavage of the phosphodiester bridge, and to develop a stable vaccine with longer shelf life in liquid formulation. Here, we generate a series of non-acetylated carbaMenA oligomers which are proven more stable than the CPS. An octamer (DP8) inhibits the binding of a MenA specific bactericidal mAb and polyclonal serum to the CPS, and is selected for further in vivo testing. However, its CRM197 conjugate raises murine antibodies towards the non-acetylated CPS backbone, but not the natural acetylated form. Accordingly, random O-acetylation of the DP8 is performed, resulting in a structure (Ac-carbaMenA) showing improved inhibition of anti-MenA CPS antibody binding and, after conjugation to CRM197, eliciting anti-MenA protective murine antibodies, comparably to the vaccine benchmark.

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mentioning

confidence: 99%

A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

Enotarpi

Tontini²,

Balocchi³

et al. 2020

Nat Commun

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“…The in silico analysis showed that MenX oligosaccharides display flexibility around the different torsional angles. Starting from this basic information provided by the calculations, the minimal MenX CPS portion able to recognize the functional MenX.01 mAb ( Sharma et al, 2019 ) was empirically determined. We produced oligomers of different lengths, that is, average degree of polymerization (avDP) starting from the CPS.…”

Section: Resultsmentioning

confidence: 99%

Elucidating the Structural and Minimal Protective Epitope of the Serogroup X Meningococcal Capsular Polysaccharide

Pietri

Tontini

Brogioni

et al. 2021

Front. Mol. Biosci.

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Despite the considerable progress toward the eradication of meningococcal disease with the introduction of glycoconjugate vaccines, previously unremarkable serogroup X has emerged in recent years, recording several outbreaks throughout the African continent. Different serogroup X polysaccharide-based vaccines have been tested in preclinical trials, establishing the principles for further improvement. To elucidate the antigenic determinants of the MenX capsular polysaccharide, we generated a monoclonal antibody, and its bactericidal nature was confirmed using the rabbit serum bactericidal assay. The antibody was tested by the inhibition enzyme-linked immunosorbent assay and surface plasmon resonance against a set of oligosaccharide fragments of different lengths. The epitope was shown to be contained within five to six α-(1–4) phosphodiester mannosamine repeating units. The molecular interactions between the protective monoclonal antibody and the MenX capsular polysaccharide fragment were further detailed at the atomic level by saturation transfer difference nuclear magnetic resonance (NMR) spectroscopy. The NMR results were used for validation of the in silico docking analysis between the X-ray crystal structure of the antibody (Fab fragment) and the modeled hexamer oligosaccharide. The antibody recognizes the MenX fragment by binding all six repeating units of the oligosaccharide via hydrogen bonding, salt bridges, and hydrophobic interactions. In vivo studies demonstrated that conjugates containing five to six repeating units can produce high functional antibody levels. These results provide an insight into the molecular basis of MenX vaccine-induced protection and highlight the requirements for the epitope-based vaccine design.

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“…Immunochemical techniques such as ELISA using antigen-specific antibodies are commonly developed as in vitro potency assays of recombinant protein and inactivated vaccine antigens. 58,59 These in vitro potency assays can serve as surrogates for in vivo immunogenicity results when in vitro-in vivo correlations are established. 60 Similar to physicochemical methods, physical adsorption of antigens onto an aluminum adjuvant poses challenges in developing in vitro potency assays.…”

Section: Development Of Competitive Elisa Assays For Four Different A...mentioning

confidence: 99%

Analytical and Preformulation Characterization Studies of Human Papillomavirus Virus-Like Particles to Enable Quadrivalent Multi-Dose Vaccine Formulation Development

Jerajani

Wan

Hickey

et al. 2022

Journal of Pharmaceutical Sciences

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Evaluation of impact of temperature and pH alterations on the size and antigenicity of meningococcal serogroup A and X polysaccharides and conjugates

Cited by 6 publications

References 14 publications

A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

Elucidating the Structural and Minimal Protective Epitope of the Serogroup X Meningococcal Capsular Polysaccharide

Analytical and Preformulation Characterization Studies of Human Papillomavirus Virus-Like Particles to Enable Quadrivalent Multi-Dose Vaccine Formulation Development

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