Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines
Some bovine antibodies across all classes are unique, such as the CDR3 of the variable heavy-domain (VH CDR3), which is exceptionally long (up to 66 amino acids), unlike most conventional antibodies where the VH CDR3 loops range from 10 to 25 amino acids. The exceptionally long VH CDR3 is encoded by...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-05-01
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| Series: | Antibodies |
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| Online Access: | http://www.mdpi.com/2073-4468/3/2/205 |
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| author | Madhuri Koti Surinder S. Saini Ashish Sachan Azad K. Kaushik |
| author_facet | Madhuri Koti Surinder S. Saini Ashish Sachan Azad K. Kaushik |
| author_sort | Madhuri Koti |
| collection | DOAJ |
| description | Some bovine antibodies across all classes are unique, such as the CDR3 of the variable heavy-domain (VH CDR3), which is exceptionally long (up to 66 amino acids), unlike most conventional antibodies where the VH CDR3 loops range from 10 to 25 amino acids. The exceptionally long VH CDR3 is encoded by unusually long germline IGHD genes together with insertion of novel “a” nucleotide rich conserved short nucleotide sequence (CSNS) specifically at the IGH V-D junction. Such an exceptionally long VH CDR3 confers unique “knob and stalk” structural architecture where the knob, formed by intra-VH CDR3 disulfide bridges, is separated by 20 Å solvent exposed stalk composed of anti-parallel beta strands. The substitution of the knob with cytokines, such as, erythropoietin and granulocyte colony stimulating factor 3 (granulocyte colony stimulating factor), results in expression of functional fusion proteins with enhanced pharmacokinetics. The beta stranded stalk can be substituted with other rigid structures, for example, repeat alpha helices to form coiled-coil that mimics the beta-stranded stalk and, thus, opens opportunities for insertion of this structure in the CDRs of antibodies across species. Given the versatility of such a structural platform in bovine antibody VH CDR3, it provides the opportunity for the development of new generation of diagnostics, therapeutics, vaccines and immunomodulating drugs. |
| first_indexed | 2024-04-12T00:14:32Z |
| format | Article |
| id | doaj.art-15b633cef81e453090fd1b18c2668ef1 |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-04-12T00:14:32Z |
| publishDate | 2014-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-15b633cef81e453090fd1b18c2668ef12022-12-22T03:55:51ZengMDPI AGAntibodies2073-44682014-05-013220521410.3390/antib3020205antib3020205Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and VaccinesMadhuri Koti0Surinder S. Saini1Ashish Sachan2Azad K. Kaushik3Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L3N6, CanadaMeat Hygiene Division, Canadian Food Inspection Agency, 1400 Merivale Road, Ottawa, ON K1A 0Y9, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, CanadaSome bovine antibodies across all classes are unique, such as the CDR3 of the variable heavy-domain (VH CDR3), which is exceptionally long (up to 66 amino acids), unlike most conventional antibodies where the VH CDR3 loops range from 10 to 25 amino acids. The exceptionally long VH CDR3 is encoded by unusually long germline IGHD genes together with insertion of novel “a” nucleotide rich conserved short nucleotide sequence (CSNS) specifically at the IGH V-D junction. Such an exceptionally long VH CDR3 confers unique “knob and stalk” structural architecture where the knob, formed by intra-VH CDR3 disulfide bridges, is separated by 20 Å solvent exposed stalk composed of anti-parallel beta strands. The substitution of the knob with cytokines, such as, erythropoietin and granulocyte colony stimulating factor 3 (granulocyte colony stimulating factor), results in expression of functional fusion proteins with enhanced pharmacokinetics. The beta stranded stalk can be substituted with other rigid structures, for example, repeat alpha helices to form coiled-coil that mimics the beta-stranded stalk and, thus, opens opportunities for insertion of this structure in the CDRs of antibodies across species. Given the versatility of such a structural platform in bovine antibody VH CDR3, it provides the opportunity for the development of new generation of diagnostics, therapeutics, vaccines and immunomodulating drugs.http://www.mdpi.com/2073-4468/3/2/205antibodyscFvexceptionally long VH CDR3antigenizationimmunomodulationvirus neutralizationvaccineimmunotherapeutics |
| spellingShingle | Madhuri Koti Surinder S. Saini Ashish Sachan Azad K. Kaushik Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines Antibodies antibody scFv exceptionally long VH CDR3 antigenization immunomodulation virus neutralization vaccine immunotherapeutics |
| title | Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines |
| title_full | Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines |
| title_fullStr | Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines |
| title_full_unstemmed | Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines |
| title_short | Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines |
| title_sort | engineered bovine antibodies in the development of novel therapeutics immunomodulators and vaccines |
| topic | antibody scFv exceptionally long VH CDR3 antigenization immunomodulation virus neutralization vaccine immunotherapeutics |
| url | http://www.mdpi.com/2073-4468/3/2/205 |
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