Refocusing of B-cell responses following a single amino acid substitution in an antigen
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...
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| Formato: | Journal Article |
| Lenguaje: | inglés |
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2018
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| Acceso en línea: | https://demo7.dspace.org/handle/123456789/212 |
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| _version_ | 1860822454993158144 |
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| author | Simmons, Cameron |
| author_browse | Simmons, Cameron |
| author_facet | Simmons, Cameron |
| author_sort | Simmons, Cameron |
| collection | DSpace |
| description | 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. |
| format | Journal Article |
| id | oai:localhost:123456789-212 |
| institution | DSPACE.FCHPT |
| language | English |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| record_format | dspace |
| spelling | oai:localhost:123456789-2122021-04-07T16:30:08Z Refocusing of B-cell responses following a single amino acid substitution in an antigen Simmons, Cameron 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. 2018-09-14T11:15:08Z 2017-07-05T04:30:54Z 2018-09-14T11:15:08Z 2001-06-01 Journal Article https://demo7.dspace.org/handle/123456789/212 English |
| spellingShingle | Simmons, Cameron Refocusing of B-cell responses following a single amino acid substitution in an antigen |
| title | Refocusing of B-cell responses following a single amino acid substitution in an antigen |
| title_full | Refocusing of B-cell responses following a single amino acid substitution in an antigen |
| title_fullStr | Refocusing of B-cell responses following a single amino acid substitution in an antigen |
| title_full_unstemmed | Refocusing of B-cell responses following a single amino acid substitution in an antigen |
| title_short | Refocusing of B-cell responses following a single amino acid substitution in an antigen |
| title_sort | refocusing of b cell responses following a single amino acid substitution in an antigen |
| url | https://demo7.dspace.org/handle/123456789/212 |
| work_keys_str_mv | AT simmonscameron refocusingofbcellresponsesfollowingasingleaminoacidsubstitutioninanantigen |