Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile
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ORIGINAL ARTICLE
Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile A.D. Cox 1
&
F. St. Michael 1 & A. Aubry 1 & P.C.R. Strong 1 & A.C. Hayes 1 & S.M. Logan 1
Received: 8 May 2020 / Revised: 6 July 2020 / Accepted: 23 July 2020 # Crown 2020
Abstract Two known Clostridiodes (Clostridium) difficile surface antigens, a lipoteichoic acid (LTA) and a polysaccharide (PS-II) were isolated and purified in order to prepare glycoconjugate vaccines to the carrier protein human serum albumin utilising a reductive amination strategy. Mice and rabbits were immunized with a prime and two boost strategy and the resulting sera were examined for their ability to recognise the purified homologous antigens and subsequently killed whole cells of C. difficile strains and other Clostridia species. Immunisation derived antisera from rabbits and mice, recognised all strains of C. difficile vegetative cells examined, with generally similar titers from animals that received the LTA or the PS-II conjugates. Sera raised to the LTA conjugates were able to recognise other Clostridia species C. butyricum, C. bifermentans and C. subterminale whereas sera raised to the PS-II conjugates were not. These LTA and PS-II sera recognised live cells in an immunofluorescence assay and were also able to recognise the spore form of the bacterium. This study has confirmed that the LTA and PS-II polysaccharides are both highly conserved surface polymers of C. difficile that are easily accessible to the immune system and as such may have potential as vaccine antigens or as targets for therapeutics to combat C. difficile infection. Keywords Clostridiodes difficile . Conjugate vaccine . Lipoteichoic acid . Capsular polysaccharide PS-II
Introduction Clostridiodes (Clostridium) difficile is a Gram-positive bacterium that is one of the most common causes of hospital acquired infection, particularly following antibiotic treatment [1]. One approach to combat this pathogen is the development of new antimicrobial agents [2], however this may be short sighted given that the emergence of C. difficile is clearly related to antibiotic usage [3]. Several other approaches are also being considered to combat C. difficile associated disease (CDAD). The majority of these approaches are focused on the generation or provision of antibodies to neutralize the toxins which are the key virulence factors produced by the bacterium [4, 5]. These toxins cause the pathology observed in CDAD which includes diarrhea, and other serious complications such as pseudomembranous colitis [6]. Antibody facilitated
* A.D. Cox [email protected] 1
Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, Ottawa, ON K1A 0R6, Canada
neutralization of toxicity will ease clinical symptoms, but anti-toxin methodologies do not directly impact the pathogen and will probably not help eradicate the bacterium. Recurrent C. difficile infection is acknowledged as a serious issue and as such it is vital that as we
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