Publication:
Refocusing of B-cell responses following a single amino acid substitution in an antigen

dc.contributor.author Simmons, Cameron
dc.date.accessioned 2018-09-14T11:15:08Z
dc.date.available 2017-07-05T04:30:54Z
dc.date.available 2018-09-14T11:15:08Z
dc.date.issued 2001-06-01 en_US
dc.description.abstract Intranasal immunization of BALB/c strain mice was carried out using baculovirus-derived human chorionic gonadotrophin (hCG) beta-chain, together with Escherichia coli heat-labile enterotoxin. Gonadotrophin-reactive immunoglobulin A (IgA) was induced in a remote mucosal site, the lung, in addition to a systemic IgG response. The extensive sequence homology with luteinizing hormone (LH) results in the production of LH cross-reactive antibodies when holo-hCG is used as an immunogen. In contrast to wild-type hCGbeta, a mutated hCGbeta-chain containing an arginine to glutamic acid substitution at position 68 did not induce the production of antibodies which cross-react with LH. Furthermore, the epitopes utilized in the B-cell response to the mutated hCGbeta shifted away from the immunodominant region of the parent wild-type molecule towards epitopes within the normally weakly immunogenic C terminus. This shift in epitope usage was also seen following intramuscular immunization of rabbits. Thus, a single amino acid change, which does not disrupt the overall structure of the molecule, refocuses the immune response away from a disadvantageous cross-reactive epitope region and towards a normally weakly immunogenic but antigen-unique area. Similar mutational strategies for epitope-refocusing may be applicable to other vaccine candidate molecules.
dc.identifier.uri https://demo7.dspace.org/handle/10673/212
dc.language English en_US
dc.title Refocusing of B-cell responses following a single amino acid substitution in an antigen en_US
dc.type Journal Article
dspace.entity.type Publication
relation.isAuthorOfPublication b1b2c768-bda1-448a-a073-fc541e8b24d9
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