Literature DB >> 23853206

The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions.

Peter D Cooper1, Thomas G Barclay, Milena Ginic-Markovic, Nikolai Petrovsky.   

Abstract

In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous → alpha-1 (AI-1) → alpha-2 (AI-2) → gamma (GI) → delta (DI) → zeta (ZI) → epsilon (EI) → omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using (1)H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) "melting" or "freezing" points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.

Entities:  

Keywords:  adjuvant; carbohydrate; inulin; isoform; vaccine

Mesh:

Substances:

Year:  2013        PMID: 23853206      PMCID: PMC3766280          DOI: 10.1093/glycob/cwt053

Source DB:  PubMed          Journal:  Glycobiology        ISSN: 0959-6658            Impact factor:   4.313


  23 in total

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Journal:  Vaccine       Date:  2011-07-06       Impact factor: 3.641

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Journal:  Vaccine       Date:  2012-06-17       Impact factor: 3.641

7.  Analysis of the hydrolysis of inulin using real time 1H NMR spectroscopy.

Authors:  Thomas Barclay; Milena Ginic-Markovic; Martin R Johnston; Peter D Cooper; Nikolai Petrovsky
Journal:  Carbohydr Res       Date:  2012-03-10       Impact factor: 2.104

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Journal:  J Virol       Date:  2013-02-06       Impact factor: 5.103

9.  The anti-melanoma activity of inulin in mice.

Authors:  P D Cooper; M Carter
Journal:  Mol Immunol       Date:  1986-08       Impact factor: 4.407

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  19 in total

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Journal:  Vaccine       Date:  2014-06-21       Impact factor: 3.641

2.  Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: a randomized controlled Phase 1 study.

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Journal:  Vaccine       Date:  2014-09-27       Impact factor: 3.641

3.  Polysaccharide PCP-I isolated from Poria cocos enhances the immunogenicity and protection of an anthrax protective antigen-based vaccine.

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Journal:  Hum Vaccin Immunother       Date:  2019-12-06       Impact factor: 3.452

4.  Physical characterization and in silico modeling of inulin polymer conformation during vaccine adjuvant particle formation.

Authors:  Thomas G Barclay; Harinda Rajapaksha; Alagu Thilagam; Gujie Qian; Milena Ginic-Markovic; Peter D Cooper; Andrea Gerson; Nikolai Petrovsky
Journal:  Carbohydr Polym       Date:  2016-01-29       Impact factor: 9.381

5.  Inulin isoforms differ by repeated additions of one crystal unit cell.

Authors:  Peter D Cooper; Thomas G Barclay; Milena Ginic-Markovic; Andrea R Gerson; Nikolai Petrovsky
Journal:  Carbohydr Polym       Date:  2013-12-31       Impact factor: 9.381

6.  Inulin crystal initiation via a glucose-fructose cross-link of adjacent polymer chains: atomic force microscopy and static molecular modelling.

Authors:  Peter D Cooper; K Harinda Rajapaksha; Thomas G Barclay; Milena Ginic-Markovic; Andrea R Gerson; Nikolai Petrovsky
Journal:  Carbohydr Polym       Date:  2014-10-23       Impact factor: 9.381

7.  Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

Authors:  Brandon Feinen; Nikolai Petrovsky; Anita Verma; Tod J Merkel
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8.  Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity.

Authors:  P D Cooper; T G Barclay; M Ginic-Markovic; N Petrovsky
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9.  Adjuvant selection impacts the correlates of vaccine protection against Ebola infection.

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Review 10.  Advax™, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety.

Authors:  Nikolai Petrovsky; Peter D Cooper
Journal:  Vaccine       Date:  2015-09-25       Impact factor: 3.641

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