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Characterization of a novel protective monoclonal antibody that recognises an epitope common to Vibrio cholerae Ogawa and Inaba serotypes

Dartmouth Medical School

ABSTRACT

A novel protective monoclonal antibody (mAb) that recognises a lipopolysaccharide (LPS) epitope common between serotypes Ogawa and Inaba of the O1 serogroup of Vibrio cholerae was characterised and the potential to develop peptide mimics of this protective LPS epitope was investigated. MAb 72.1 recognises both Ogawa and Inaba LPS and it is vibriocidal and protective in passive immunization against infection by strains of both serotypes. The cDNA derived amino acid sequence of mAb 72.1 is closely related to the previously characterised mAb ZAC-3, which is thought to recognise an epitope in the lipid A-core region of O1 LPS. In an attempt to develop a peptide mimic based vaccine against V. cholerae, phage display libraries were screened with mAb 72.1 and eleven peptide mimics were identified. Remarkably, all of the peptide sequences identified from linear phage display libraries contained two cysteine residues suggesting that mAb 72.1 preferentially binds to peptides constrained with a disulphide bond. One of the peptide mimics was immunologically characterised. Although immunization of mice with this peptide mimic conjugated to KLH elicited Abs against the peptide itself, these Abs did not cross-react with Ogawa or Inaba LPS. Effectiveness of a peptide mimic as a vaccine may depend on how well the peptide can mimic the carbohydrate interactions when binding to the anti-carbohydrate Ab. Thus, investigating how peptides and LPS bind to mAb 72.1 may be useful in improving current peptide mimics or designing more effective peptide mimics. Identification and characterisation of novel protective anti-LPS Abs may be useful in studying protective epitopes of LPS which may help develop LPS based therapeutics against V. cholerae.

¹ E-mail: ronald.k.taylor{at}dartmouth.edu