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

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

1, 2, 3 and 3,* email
Received: 24 February 2014; in revised form: 5 April 2014 / Accepted: 25 April 2014 / Published: 9 May 2014
(This article belongs to the Special Issue Antibody Engineering)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: 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.

AMA Style

Koti M, Saini SS, Sachan A, Kaushik AK. Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines. Antibodies. 2014; 3(2):205-214.

Chicago/Turabian Style

Koti, Madhuri; Saini, Surinder S.; Sachan, Ashish; Kaushik, Azad K. 2014. "Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines." Antibodies 3, no. 2: 205-214.

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