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Antibodies 2014, 3(2), 205-214; doi:10.3390/antib3020205

Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines

1
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L3N6, Canada
2
Meat Hygiene Division, Canadian Food Inspection Agency, 1400 Merivale Road, Ottawa, ON K1A 0Y9, Canada
3
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada
*
Author to whom correspondence should be addressed.
Received: 24 February 2014 / Revised: 5 April 2014 / Accepted: 25 April 2014 / Published: 9 May 2014
(This article belongs to the Special Issue Antibody Engineering)
View Full-Text   |   Download PDF [428 KB, 26 May 2014; original version 9 May 2014]   |  

Abstract

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. View Full-Text
Keywords: antibody; scFv; exceptionally long VH CDR3; antigenization; immunomodulation; virus neutralization; vaccine; immunotherapeutics antibody; scFv; exceptionally long VH CDR3; antigenization; immunomodulation; virus neutralization; vaccine; immunotherapeutics
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MDPI and ACS Style

Koti, M.; Saini, S.S.; Sachan, A.; Kaushik, A.K. Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines. Antibodies 2014, 3, 205-214.

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