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Review

Breaking barriers in antibody discovery: harnessing divergent species for accessing difficult and conserved drug targets

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Article: 2273018 | Received 31 May 2023, Accepted 16 Oct 2023, Published online: 05 Dec 2023

References

  • Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, Wu HC. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27:1. doi:10.1186/s12929-019-0592-z. PMID: 31894001.
  • Kaplon H, Reichert JM. Antibodies to watch in 2021. MAbs. 2021;13:1860476. doi:10.1080/19420862.2020.1860476. PMID: 33459118.
  • Kaplon H, Chenoweth A, Crescioli S, Reichert JM. Antibodies to watch in 2022. MAbs. 2022;14:2014296. doi:10.1080/19420862.2021.2014296. PMID: 35030985.
  • Carter PJ, Lazar GA. Next generation antibody drugs: pursuit of the ‘high-hanging fruit’. Nat Rev Drug Discov. 2018;17(3):197–14. PMID: 29192287. doi: 10.1038/nrd.2017.227.
  • Jain T, Sun T, Durand S, Hall A, Houston NR, Nett JH, Sharkey B, Bobrowicz B, Caffry I, Yu Y, et al. Biophysical properties of the clinical-stage antibody landscape. Proceedings of the National Academy of Sciences of the United States of America. 2017; 114:944–49. doi:10.1073/pnas.1616408114. PMID: 28096333.
  • Abdiche YN, Harriman R, Deng X, Yeung YA, Miles A, Morishige W, Boustany L, Zhu L, Izquierdo SM, Harriman W. Assessing kinetic and epitopic diversity across orthogonal monoclonal antibody generation platforms. MAbs. 2016;8:264–77. doi:10.1080/19420862.2015.1118596. PMID: 26652308.
  • Verbruggen B, Gunnarsson L, Kristiansson E, Osterlund T, Owen SF, Snape JR, Tyler CR. Ecodrug: a database connecting drugs and conservation of their targets across species. Nucleic Acids Res. 2018;46:D930–D36. doi:10.1093/nar/gkx1024. PMID: 29140522.
  • Hedges SB. The origin and evolution of model organisms. Nat Rev Genet. 2002;3:838–49. doi:10.1038/nrg929. PMID: 12415314.
  • International Chicken Genome Sequencing C. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature. 2004;432:695–716. PMID: 15592404. doi:10.1038/nature03154
  • Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–97. doi:10.1038/256495a0. PMID: 1172191.
  • Tucker DF, Sullivan JT, Mattia KA, Fisher CR, Barnes T, Mabila MN, Wilf R, Sulli C, Pitts M, Payne RJ, et al. Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115:E4990–E99. doi:10.1073/pnas.1716788115. PMID: 29769329.
  • Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, Chae PS, Devree BT, Rosenbaum DM, Thian FS, Kobilka TS, et al. Structure of a nanobody-stabilized active state of the β2 adrenoceptor. Nature. 2011;469(7329):175–80. PMID: 21228869. doi:10.1038/nature09648.
  • Mujic-Delic A, RH DW, Verkaar F, MJ S. GPCR-targeting nanobodies: attractive research tools, diagnostics, and therapeutics. Trends Pharmacol Sci. 2014;35(5):247–55. PMID: 24690241. doi: 10.1016/j.tips.2014.03.003.
  • Screnci B, Stafford LJ, Barnes T, Shema K, Gilman S, Wright R, Al Absi S, Phillips T, Azuelos C, Slovik K, et al. Antibody specificity against highly conserved membrane protein Claudin 6 driven by single atomic contact point. iScience. 2022;25:105665. doi:10.1016/j.isci.2022.105665. PMID: 36505931.
  • Liu S, Wang S, Lu S. DNA immunization as a technology platform for monoclonal antibody induction. Emerg Microbes Infect. 2016;5:e33. doi:10.1038/emi.2016.27. PMID: 27048742.
  • Beck A, Goetsch L, Dumontet C, Corvaia N. Strategies and challenges for the next generation of antibody–drug conjugates. Nat Rev Drug Discov. 2017;16(5):315–37. PMID: 28303026. doi: 10.1038/nrd.2016.268.
  • Marks JD, Bradbury A. Selection of human antibodies from phage display libraries. Methods Mol Biol. 2004;248:161–76. doi:10.1385/1-59259-666-5:161. PMID: 14970495.
  • Shehata L, Maurer DP, Wec AZ, Lilov A, Champney E, Sun T, Archambault K, Burnina I, Lynaugh H, Zhi X, et al. Affinity maturation enhances antibody specificity but compromises conformational stability. Cell Reports. 2019;28(13):3300–8 e3304. PMID: 31553901. doi:10.1016/j.celrep.2019.08.056.
  • Prabakaran P, Rao SP, Wendt M. Animal immunization merges with innovative technologies: a new paradigm shift in antibody discovery. MAbs. 2021;13:1924347. doi:10.1080/19420862.2021.1924347. PMID: 33947305.
  • Ablynx Ghent B. CABLIVI [package insert]. 2023.
  • Novartis East Hanover NJ. BEOVU [package insert]. 2022.
  • Lundbeck Seattle BioPharmaceuticals IB, WA. VYEPTI [prescribing information]. 2022.
  • Tabs - therapeutic antibody database. https://tabs.craic.com/users. Date [accessed 2020-2023].
  • Edwards BM, Barash SC, Main SH, Choi GH, Minter R, Ullrich S, Williams E, Du Fou L, Wilton J, Albert VR, et al. The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BLyS. J Mol Biol. 2003;334:103–18. doi:10.1016/j.jmb.2003.09.054. PMID: 14596803.
  • Madabushi S, Gross AK, Philippi A, Meng EC, Wensel TG, Lichtarge O. Evolutionary trace of G protein-coupled receptors reveals clusters of residues that determine global and class-specific functions. J Biol Chem. 2004;279:8126–32. doi:10.1074/jbc.M312671200. PMID: 14660595.
  • Lichtarge O, Bourne HR, Cohen FE. An evolutionary trace method defines binding surfaces common to protein families. J Mol Biol. 1996;257:342–58. doi:10.1006/jmbi.1996.0167. PMID: 8609628.
  • Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, et al. Genome sequence of the brown Norway rat yields insights into mammalian evolution. Nature. 2004;428:493–521. doi:10.1038/nature02426. PMID: 15057822.
  • Finlay WJ, Bloom L, Varghese S, Autin B, Cunningham O. Optimized generation of high-affinity, high-specificity single-chain fv antibodies from multi-antigen immunized chickens. Methods Mol Biol. 2017;1485:319–38. doi:10.1007/978-1-4939-6412-3_16. PMID: 27730560.
  • De Genst E, Silence K, Decanniere K, Conrath K, Loris R, Kinne J, Muyldermans S, Wyns L Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103:4586–91. doi:10.1073/pnas.0505379103. PMID: 16537393.
  • Stave JW, Lindpaintner K. Antibody and antigen contact residues define epitope and paratope size and structure. J Immunol. 2013;191(3):1428–35. PMID: 23797669. doi: 10.4049/jimmunol.1203198.
  • JA F, Koehler LJ, JR W, Cisneros A, JE C, Meiler J. Improving loop modeling of the antibody complementarity-determining region 3 using knowledge-based restraints. PloS One. 2016;11(5):e0154811. PMID: 27182833. doi: 10.1371/journal.pone.0154811.
  • Ramsland PA, Kaushik A, Marchalonis JJ, Edmundson AB. Incorporation of long CDR3s into V domains: implications for the structural evolution of the antibody-combining site. Exp Clin Immunogenet. 2001;18:176–98. doi:10.1159/000049197. PMID: 11872949.
  • Garces F, Mohr C, Zhang L, Huang CS, Chen Q, King C, Xu C, Wang Z. Molecular insight into recognition of the CGRPR complex by migraine prevention therapy aimovig (erenumab). Cell Reports. 2020;30(6):1714–23 e1716. PMID: 32049005. doi: 10.1016/j.celrep.2020.01.029.
  • Barnes CO, Jette CA, Abernathy ME, Dam KA, Esswein SR, Gristick HB, Malyutin AG, Sharaf NG, Huey-Tubman KE, Lee YE, et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 2020;588(7839):682–87. PMID: 33045718. doi:10.1038/s41586-020-2852-1.
  • Ma Y, Ding Y, Song X, Ma X, Li X, Zhang N, Song Y, Sun Y, Shen Y, Zhong W, et al. Structure-guided discovery of a single-domain antibody agonist against human apelin receptor. Sci Adv. 2020;6(3):eaax7379. PMID: 31998837. doi:10.1126/sciadv.aax7379.
  • Lavinder JJ, Hoi KH, Reddy ST, Wine Y, Georgiou G. Systematic characterization and comparative analysis of the rabbit immunoglobulin repertoire. PloS One. 2014;9(6):e101322. PMID: 24978027. doi: 10.1371/journal.pone.0101322.
  • Wu L, Oficjalska K, Lambert M, Fennell BJ, Darmanin-Sheehan A, Ni Shuilleabhain D, Autin B, Cummins E, Tchistiakova L, Bloom L, et al. Fundamental characteristics of the immunoglobulin VH repertoire of chickens in comparison with those of humans, mice, and camelids. J Immunol. 2012;188(1):322–33. PMID: 22131336. doi:10.4049/jimmunol.1102466.
  • Wu TT, Johnson G, Kabat EA. Length distribution of CDRH3 in antibodies. Proteins. 1993;16:1–7. doi:10.1002/prot.340160102. PMID: 8497480.
  • Muyldermans S, Smider VV. Distinct antibody species: structural differences creating therapeutic opportunities. Curr Opin Immunol. 2016;40:7–13. doi:10.1016/j.coi.2016.02.003. PMID: 26922135.
  • Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell. 2005;7:301–11. doi:10.1016/j.ccr.2005.03.003. PMID: 15837620.
  • ICH S6. Preclinical safety evaluation of biotechnology-derived pharmaceuticals. https://www.ich.org/. Date [accessed May 4, 2022].
  • ICH harmonisation for better health: safety guidelines, biotechnology products. https://www.ich.org/page/safety-guidelines. Date [accessed May 42022].
  • Bussiere JL, Martin P, Horner M, Couch J, Flaherty M, Andrews L, Beyer J, Horvath C. Alternative strategies for toxicity testing of species-specific biopharmaceuticals. Int J Toxicol. 2009;28:230–53. doi:10.1177/1091581809337262. PMID: 19546261.
  • Sewell F, Chapman K, Couch J, Dempster M, Heidel S, Loberg L, Maier C, Maclachlan TK, Todd M, van der Laan JW. Challenges and opportunities for the future of monoclonal antibody development: improving safety assessment and reducing animal use. MAbs. 2017;9:742–55. doi:10.1080/19420862.2017.1324376. PMID: 28475417.
  • Collins FS NIH will no longer support biomedical research on chimpanzees. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-will-no-longer-support-biomedical-research-chimpanzees. 2015 Date [accessed November 22, 2021].
  • GUIDANCE DOCUMENT: nonclinical considerations for mitigating nonhuman primate supply constraints arising from the COVID-19 pandemic. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/nonclinical-considerations-mitigating-nonhuman-primate-supply-constraints-arising-covid-19-pandemic 2022 Date [accessed May 4, 2022].
  • Zhang S. America is running low on a crucial resource for COVID-19 vaccines. The Atlantic. 2020 2020; August 13. https://www.theatlantic.com/science/archive/2020/08/america-facing-monkey-shortage/615799/.
  • Food and Drug Administration. Caplacizumab. Center for drug evaluation and research application number: 761112Orig1s000 multi-discipline Review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761112Orig1s000MultiR.pdf. Date [accessed April 11, 2022].
  • Food and Drug Administration. Brolucizumab. Center for drug evaluation and research application number 761125Orig1s000. Non-Clinical Review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000PharmR.pdf. 2019 Date [accessed April 11, 2022].
  • Food and Drug Administration. Eptinezumab. Center for drug evaluation and research application number: 761119Orig1s000 non-clinical Review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761119Orig1s000PharmR.pdf. Date [accessed April 11, 2022].
  • Gjetting T, Gad M, Frohlich C, Lindsted T, Melander MC, Bhatia VK, Grandal MM, Dietrich N, Uhlenbrock F, Galler GR, et al. Sym021, a promising anti-PD1 clinical candidate antibody derived from a new chicken antibody discovery platform. MAbs. 2019;11:666–80. doi:10.1080/19420862.2019.1596514. PMID: 31046547.
  • Stack E, McMurray S, McMurray G, Wade J, Clark M, Young G, Marquette K, Jain S, Kelleher K, Chen T, et al. In vitro affinity optimization of an anti-BDNF monoclonal antibody translates to improved potency in targeting chronic pain states in vivo. MAbs. 2020;12:1755000. doi:10.1080/19420862.2020.1755000. PMID: 32329655.
  • Shih HH, Tu C, Cao W, Klein A, Ramsey R, Fennell BJ, Lambert M, Ni Shuilleabhain D, Autin B, Kouranova E, et al. An ultra-specific avian antibody to phosphorylated tau protein reveals a unique mechanism for phosphoepitope recognition. Journal Of Biological Chemistry. 2012;287(53):44425–34. PMID: 23148212. doi:10.1074/jbc.M112.415935.
  • Chockalingam K, Kumar A, Song J, Chen Z. Chicken-derived CD20 antibodies with potent B-cell depletion activity. Br J Haematol. 2022;199:560–71. doi:10.1111/bjh.18438. PMID: 36039695.
  • Yokosaki Y, Nishimichi N. New therapeutic targets for hepatic fibrosis in the integrin family, α8β1 and α11β1, induced specifically on activated stellate cells. Int J Mol Sci. 2021;22(23):12794. PMID: 34884600. doi: 10.3390/ijms222312794.
  • Sim J, Sockolosky JT, Sangalang E, Izquierdo S, Pedersen D, Harriman W, Wibowo AS, Carter J, Madan A, Doyle L, et al. Discovery of high affinity, pan-allelic, and pan-mammalian reactive antibodies against the myeloid checkpoint receptor SIRPα. MAbs. 2019;11(6):1036–52. PMID: 31257988. doi:10.1080/19420862.2019.1624123.
  • Konitzer JD, Pramanick S, Pan Q, Augustin R, Bandholtz S, Harriman W, Izquierdo S. Generation of a highly diverse panel of antagonistic chicken monoclonal antibodies against the GIP receptor. MAbs. 2017;9:536–49. doi:10.1080/19420862.2016.1276683. PMID: 28055305.
  • Xiang Y, Sang Z, Bitton L, Xu J, Liu Y, Schneidman-Duhovny D, Shi Y. Integrative proteomics identifies thousands of distinct, multi-epitope, and high-affinity nanobodies. Cell Syst. 2021;12(3):220–34 e229. PMID: 33592195. doi: 10.1016/j.cels.2021.01.003.
  • Weber J, Peng H, Rader C. From rabbit antibody repertoires to rabbit monoclonal antibodies. Experimental & Molecular Medicine. 2017;49:e305. doi:10.1038/emm.2017.23. PMID: 28336958.
  • Zhang Z, Liu H, Guan Q, Wang L, Yuan H. Advances in the isolation of specific monoclonal rabbit antibodies. Front Immunol. 2017;8:494. doi:10.3389/fimmu.2017.00494. PMID: 28529510.
  • Yu Y, Lee P, Ke Y, Zhang Y, Yu Q, Lee J, Li M, Song J, Chen J, Dai J, et al. A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models. PloS One. 2010;5:e9072. doi:10.1371/journal.pone.0009072. PMID: 20140208.
  • Popkov M, RG M, CB A, Thundivalappil S, CF B, Rader C. Rabbit immune repertoires as sources for therapeutic monoclonal antibodies: the impact of kappa allotype-correlated variation in cysteine content on antibody libraries selected by phage display. J Mol Biol. 2003;325(2):325–35. PMID: 12488098. doi: 10.1016/s0022-2836(02)01232-9.
  • Leighton PA, Morales J, Harriman WD, Ching KH. V(D)J rearrangement is dispensable for producing CDR-H3 sequence diversity in a gene converting species. Front Immunol. 2018;9:1317. doi:10.3389/fimmu.2018.01317. PMID: 29951062.
  • Kawade R, Akiba H, Entzminger K, Maruyama T, Okumura CJ, Tsumoto K. Roles of the disulfide bond between the variable and the constant domains of rabbit immunoglobulin kappa chains in thermal stability and affinity. Protein Eng Des Sel. 2018;31:243–47. doi:10.1093/protein/gzy008. PMID: 29850878.
  • Landry JP, Ke Y, Yu GL, Zhu XD. Measuring affinity constants of 1450 monoclonal antibodies to peptide targets with a microarray-based label-free assay platform. J Immunol Methods. 2015;417:86–96. doi:10.1016/j.jim.2014.12.011. PMID: 25536073.
  • Ros F, Offner S, Klostermann S, Thorey I, Niersbach H, Breuer S, Zarnt G, Lorenz S, Puels J, Siewe B, et al. Rabbits transgenic for human IgG genes recapitulating rabbit B-cell biology to generate human antibodies of high specificity and affinity. MAbs. 2020;12:1846900. doi:10.1080/19420862.2020.1846900. PMID: 33228444.
  • The antibody society. https://www.antibodysociety.org/. Date [accessed October 12, 2023].
  • Markham A. Brolucizumab: first approval. Drugs. 2019;79:1997–2000. doi:10.1007/s40265-019-01231-9. PMID: 31768932.
  • Alder BioPharmaceuticals I Annual report on form 10-K. In: Annual Report on Form 10-K. https://www.sec.gov/Archives/edgar/data/1423824/000156459019004084/aldr-10k_20181231.htm. 2019.
  • Fukuzawa T, Sampei Z, Haraya K, Ruike Y, Shida-Kawazoe M, Shimizu Y, Gan SW, Irie M, Tsuboi Y, Tai H, et al. Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases. Sci Rep. 2017;7:1080. doi:10.1038/s41598-017-01087-7. PMID: 28439081.
  • de Los Rios M, Criscitiello MF, Smider VV. Structural and genetic diversity in antibody repertoires from diverse species. Curr Opin Struct Biol. 2015;33:27–41. doi:10.1016/j.sbi.2015.06.002. PMID: 26188469.
  • Arbabi-Ghahroudi M. Camelid single-domain antibodies: historical perspective and future outlook. Front Immunol. 2017;8:1589. doi:10.3389/fimmu.2017.01589. PMID: 29209322.
  • Jovcevska I, Muyldermans S. 2020. The therapeutic potential of nanobodies. BioDrugs: clinical immunotherapeutics, biopharmaceuticals and gene therapy. PMID: 31686399 34(1):11–26. doi:10.1007/s40259-019-00392-z
  • Vincke C, Loris R, Saerens D, Martinez-Rodriguez S, Muyldermans S, Conrath K. General strategy to humanize a camelid single-domain antibody and identification of a universal humanized nanobody scaffold. J Biol Chem. 2009;284:3273–84. doi:10.1074/jbc.M806889200. PMID: 19010777.
  • Xu J, Xu K, Jung S, Conte A, Lieberman J, Muecksch F, Lorenzi JCC, Park S, Schmidt F, Wang Z, et al. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. Nature. 2021;595:278–82. doi:10.1038/s41586-021-03676-z. PMID: 34098567.
  • Lauwereys M, Arbabi Ghahroudi M, Desmyter A, Kinne J, Holzer W, De Genst E, Wyns L, Muyldermans S. Potent enzyme inhibitors derived from dromedary heavy-chain antibodies. EMBO J. 1998;17(13):3512–20. PMID: 9649422. doi: 10.1093/emboj/17.13.3512.
  • Desmyter A, Transue TR, Ghahroudi MA, Thi MH, Poortmans F, Hamers R, Muyldermans S, Wyns L. Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme. Nat Struct Biol. 1996;3:803–11. doi:10.1038/nsb0996-803. PMID: 8784355.
  • Heukers R, De Groof TWM, Smit MJ. Nanobodies detecting and modulating GPCRs outside in and inside out. Curr Opin Cell Biol. 2019;57:115–22. doi:10.1016/j.ceb.2019.01.003. PMID: 30849632.
  • Belanger K, Tanha J. High-efficacy, high-manufacturability human VH domain antibody therapeutics from transgenic sources. Protein engineering, design & selection: PEDS. 2021. 34. 10.1093/protein/gzab012. PMID: 33991089
  • Alfaleh MA, Alsaab HO, Mahmoud AB, Alkayyal AA, Jones ML, Mahler SM, Hashem AM. Phage display derived monoclonal antibodies: from bench to bedside. Front Immunol. 2020;11:1986. doi:10.3389/fimmu.2020.01986. PMID: 32983137.
  • Zhang F, Wei H, Wang X, Bai Y, Wang P, Wu J, Jiang X, Wang Y, Cai H, Xu T, et al. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade. Cell Discov. 2017;3:17004. doi:10.1038/celldisc.2017.4. PMID: 28280600.
  • Tanaka Y. Ozoralizumab: first nanobody® therapeutic for rheumatoid arthritis. Expert Opin Biol Ther. 2023;23(7):579–87. PMID: 37431762. doi: 10.1080/14712598.2023.2231344.
  • Ching KH, Collarini EJ, Abdiche YN, Bedinger D, Pedersen D, Izquierdo S, Harriman R, Zhu L, Etches RJ, van de Lavoir MC, et al. Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets. MAbs. 2018;10:71–80. doi:10.1080/19420862.2017.1386825. PMID: 29035625.
  • IMGT®, The international ImMunoGeneTics information system®. 2022 Date [accessed May 20, 2023].
  • Bednenko J, Harriman R, Marien L, Nguyen HM, Agrawal A, Papoyan A, Bisharyan Y, Cardarelli J, Cassidy-Hanley D, Clark T, et al. A multiplatform strategy for the discovery of conventional monoclonal antibodies that inhibit the voltage-gated potassium channel Kv1.3. MAbs. 2018;10:636–50. doi:10.1080/19420862.2018.1445451. PMID: 29494279.
  • Anti-MCT1 antibodies and uses thereof. WO2019136300A2;
  • Wood CAP, Zhang J, Aydin D, Xu Y, Andreone BJ, Langen UH, Dror RO, Gu C, Feng L. Structure and mechanism of blood–brain-barrier lipid transporter MFSD2A. Nature. 2021;596(7872):444–48. PMID: 34349262. doi: 10.1038/s41586-021-03782-y.
  • Handa M Designing discovery strategies to Maximize Molecular recognition to find agonist antibodies. In: Proceedings of the Discovery on Target Conference 2022; Boston: 2022.
  • Pasman Y, Soliman C, Ramsland PA, Kaushik AK. Exceptionally long CDR3H of bovine scFv antigenized with BoHV-1 B-epitope generates specific immune response against the targeted epitope. Mol Immunol. 2016;77:113–25. doi:10.1016/j.molimm.2016.07.014. PMID: 27497190.
  • Saini SS, Allore B, Jacobs RM, Kaushik A. Exceptionally long CDR3H region with multiple cysteine residues in functional bovine IgM antibodies. Eur J Immunol. 1999;29:2420–26. doi:10.1002/(SICI)1521-4141(199908)29:08<2420:AID-IMMU2420>3.0.CO;2-A. PMID: 10458755.
  • Hawkins A, Joyce C, Brady K, Hold A, Smith A, Knight M, Howard C, van den Elsen J, Lawson ADG, Macpherson A. The proximity of the N- and C- termini of bovine knob domains enable engineering of target specificity into polypeptide chains. MAbs. 2022;14:2076295. doi:10.1080/19420862.2022.2076295. PMID: 35634719.
  • Stanfield RL, Berndsen ZT, Huang R, Sok D, Warner G, Torres JL, Burton DR, Ward AB, Wilson IA, Smider VV. Structural basis of broad HIV neutralization by a vaccine-induced cow antibody. Sci Adv. 2020;6(22):eaba0468. PMID: 32518821. doi: 10.1126/sciadv.aba0468.