Development of neutralizing scFv-Fc against botulinum neurotoxin a light chain from a macaque immune library

mAbs

Volumn 6, Issue 2, 2014, Pages 446-459

  Miethe, Sebastian ^a   Rasetti Escargueil, Christine ^b   Liu, Yvonne ^b   Chahboun, Siham ^c   Pelat, Thibaut ^c   Avril, Arnaud ^c   Frenzel, André ^a   Schirrmann, Thomas ^a   Thullier, Philippe ^c   Sesardic, Dorothea ^b   Hust, Michael ^a  

^a TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

^b NATIONAL INSTITUTE FOR BIOLOGICAL STANDARDS AND CONTROL   (United Kingdom)

^c INSTITUT DE RECHERCHE BIOMÉDICALE DES ARMÉES   (France)

Author keywords

BoNT A; Botulinum neurotoxin; Clostridium botulinum; Ex vivo assay; In vitro assay; Macaca fascicularis; Macaque; Mouse phrenic nerve hemidiaphragm assay; Phage display; scFv; scFv Fc; SNAP 25

Indexed keywords

BOTULINUM TOXIN A; DNA FRAGMENT; NEUTRALIZING ANTIBODY; PROTEINASE; SE120 IIIC4; SEM 95 C6; SEM120 IIIC1; SEM120 IVC5; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG PROTEIN BINDING; ENZYME LINKED IMMUNOSORBENT ASSAY; HEMIDIAPHRAGM; IN VITRO STUDY; MACACA FASCICULARIS; MALE; NONHUMAN; PHAGE DISPLAY; PHRENIC NERVE;

BONT/A; BOTULINUM NEUROTOXIN; CLOSTRIDIUM BOTULINUM; EX-VIVO ASSAY; IN VITRO ASSAY; MACACA FASCICULARIS; MACAQUE; MOUSE PHRENIC NERVE-HEMIDIAPHRAGM ASSAY; PHAGE DISPLAY; SCFV; SCFV-FC; SNAP-25;

ANIMALS; ANTIBODIES, BLOCKING; BOTULINUM TOXINS, TYPE A; BOTULISM; CELL SURFACE DISPLAY TECHNIQUES; CLOSTRIDIUM BOTULINUM TYPE A; EPITOPE MAPPING; HUMANS; IMMUNITY; IMMUNIZATION; IMMUNOGLOBULIN FC FRAGMENTS; IMMUNOGLOBULIN LIGHT CHAINS, SURROGATE; IMMUNOTHERAPY; MACACA FASCICULARIS; MALE; MICE; MICE, INBRED BALB C; PARALYSIS; PHRENIC NERVE; SINGLE-CHAIN ANTIBODIES;

EID: 84896499135     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.27773     Document Type: Article

References (56)

1. Sobel J. Botulism. Clin Infect Dis 2005; 41:1167-73; PMID:16163636; http://dx.doi.org/10.1086/444507.
2. Fujinaga Y, Sugawara Y, Matsumura T. Uptake of botulinum neurotoxin in the intestine. Curr Top Microbiol Immunol 2013; 364:45-59; PMID:23239348.
3. Hibbs RG, Weber JT, Corwin A, Allos BM, Abd el Rehim MS, Sharkawy SE, Sarn JE, McKee KT Jr. Experience with the use of an investigational F(ab')2 heptavalent botulism immune globulin of equine origin during an outbreak of type E botulism in Egypt. Clin Infect Dis 1996; 23:337-40; PMID:8842274;http://dx. doi.org/10.1093/clinids/23.2.337.
4. Jalava K, Selby K, Pihlajasaari A, Kolho E, Dahlsten E, Forss N, Bäcklund T, Korkeala H, Honkanen-Buzalski T, Hulkko T, et al. Two cases of foodborne botulism in Finland caused by conserved olives, October 2011. Euro Surveill 2011; 16:20034; PMID:22172330.
5. Pingeon JM, Vanbockstael C, Popoff MR, King LA, Deschamps B, Pradel G, Dupont H, Spanjaard A, Houdard A, Mazuet C, et al. Two outbreaks of botulism associated with consumption of green olive paste, France, September 2011. Euro Surveill 2011; 16:20035; PMID:22172329.
6. Liu Z, Zhang C, Li Y, Song C, Sun Y, Wei Y, Xu Z, Yang A, Xu Z, Yang K, et al. High sensitivity ELISA for detection of botulinum neurotoxin serotype F. Hybridoma (Larchmt) 2012; 31:233-9; PMID:22894775;http://dx.doi.org/10.1089/hyb. 2012.0017.
7. Barash JR, Arnon SS. A Novel Strain of Clostridium botulinum That Produces Type B;Type H Botulinum Toxins. J Infect Dis 2014; 209:183-91; PMID:24106296;http://dx.doi.org/10.1093/infdis/jit449.
8. Dover N, Barash JR, Hill KK, Xie G, Arnon SS. Molecular characterization of a novel botulinum neurotoxin type h gene. J Infect Dis 2014; 209:192-202; PMID:24106295;http://dx.doi.org/10.1093/infdis/jit450.
9. Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, et al.; Working Group on Civilian Biodefense. Botulinum toxin as a biological weapon: medical;public health management. JAMA 2001; 285:1059-70; PMID:11209178;http://dx.doi.org/10.1001/ jama.285.8.1059.
10. Froude JW, Stiles B, Pelat T, Thullier P. Antibodies for biodefense. MAbs 2011; 3:517-27; PMID:22123065;http://dx.doi.org/10.4161/mabs.3.6.17621.
11. Gill DM. Bacterial toxins: a table of lethal amounts. Microbiol Rev 1982; 46:86-94; PMID:6806598.
12. Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol Rev 2000; 80:717-66; PMID:10747206.
13. Lim ECH, Seet RCS. Use of botulinum toxin in the neurology clinic. Nat Rev Neurol 2010; 6:624-36; PMID:21045798; http://dx.doi.org/10.1038/nrneurol. 2010.149
14. Smith LA. Botulism;vaccines for its prevention. Vaccine 2009; 27(Suppl 4):D33-9; PMID:19837283; http://dx.doi.org/10.1016/j.vaccine.2009.08.059.
15. Black RE, Gunn RA. Hypersensitivity reactions associated with botulinal antitoxin. Am J Med 1980; 69:567-70; PMID:7191633; http://dx.doi.org/10.1016/ 0002-9343(80)90469-6.
16. Adekar SP, Takahashi T, Jones RM, Al-Saleem FH, Ancharski DM, Root MJ, Kapadnis BP, Simpson LL, Dessain SK. Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain. PLoS ONE 2008; 3:e3023; PMID:18714390; http://dx.doi.org/10.1371/journal.pone.0003023.
17. Thanongsaksrikul J, Srimanote P, Maneewatch S, Choowongkomon K, Tapchaisri P, Makino S, Kurazono H, Chaicumpa WAVH. H that neutralizes the zinc metalloproteinase activity of botulinum neurotoxin type A. J Biol Chem 2010; 285:9657-66; PMID:20093370; http://dx.doi.org/10.1074/jbc.M109.073163.
18. Schütte M, Thullier P, Pelat T, Wezler X, Rosenstock P, Hinz D, Kirsch MI, Hasenberg M, Frank R, Schirrmann T, et al. Identification of a putative Crf splice variant;generation of recombinant antibodies for the specific detection of Aspergillus fumigatus. PLoS ONE 2009; 4:e6625; PMID:19675673; http://dx.doi.org/10.1371/journal.pone.0006625.
19. Chassagne S, Laffly E, Drouet E, Hérodin F, Lefranc M-P, Thullier P. A high-affinity macaque antibody Fab with human-like framework regions obtained from a small phage display immune library. Mol Immunol 2004; 41:539-46; PMID:15183932;http://dx.doi.org/10.1016/j.molimm.2004.03.040.
20. Pelat T, Hust M, Hale M, Lefranc M-P, Dübel S, Thullier P. Isolation of a human-like antibody fragment (scFv) that neutralizes ricin biological activity. BMC Biotechnol 2009; 9:60; PMID:19563687;http://dx.doi.org/10.1186/ 1472-6750-9-60.
21. Laffly E, Danjou L, Condemine F, Vidal D, Drouet E, Lefranc M-P, Bottex C, Thullier P. Selection of a macaque Fab with framework regions like those in humans, high affinity,;ability to neutralize the protective antigen (PA) of Bacillus anthracis by binding to the segment of PA between residues 686;694. Antimicrob Agents Chemother 2005; 49:3414-20; PMID:16048955;http://dx.doi.org/ 10.1128/AAC.49.8.3414-3420.2005.
22. Pelat T, Hust M, Laffly E, Condemine F, Bottex C, Vidal D, Lefranc M-P, Dübel S, Thullier P. Highaffinity, human antibody-like antibody fragment (single-chain variable fragment) neutralizing the lethal factor (LF) of Bacillus anthracis by inhibiting protective antigen-LF complex formation. Antimicrob Agents Chemother 2007; 51:2758-64; PMID:17517846;http://dx.doi.org/10.1128/AAC. 01528-06.
23. Kirsch MI, Hülseweh B, Nacke C, Rülker T, Schirrmann T, Marschall H-J, Hust M, Dübel S. Development of human antibody fragments using antibody phage display for the detection;diagnosis of Venezuelan equine encephalitis virus (VEEV). BMC Biotechnol 2008; 8:66; PMID:18764933;http://dx. doi.org/10.1186/1472-6750-8-66.
24. Kuwata T, Katsumata Y, Takaki K, Miura T, Igarashi T. Isolation of potent neutralizing monoclonal antibodies from an SIV-Infected rhesus macaque by phage display. AIDS Res Hum Retroviruses 2011; 27:487-500; PMID:20854170.
25. Chahboun S, Hust M, Liu Y, Pelat T, Miethe S, Helmsing S, Jones RG, Sesardic D, Thullier P. Isolation of a nanomolar scFv inhibiting the endopeptidase activity of botulinum toxin A, by single-round panning of an immune phage-displayed library of macaque origin. BMC Biotechnol 2011; 11:113; PMID:22111995;http://dx.doi.org/10.1186/1472-6750-11-113.
26. Jäger V, Büssow K, Wagner A, Weber S, Hust M, Frenzel A, Schirrmann T. High level transient production of recombinant antibodies;antibody fusion proteins in HEK293 cells. BMC Biotechnol 2013; 13:52; PMID:23802841;http://dx.doi.org/10.1186/1472-6750-13-52.
27. Hill KK, Smith TJ, Helma CH, Ticknor LO, Foley BT, Svensson RT, Brown JL, Johnson EA, Smith LA, Okinaka RT, et al. Genetic diversity among Botulinum Neurotoxin-producing clostridial strains. J Bacteriol 2007; 189:818-32; PMID:17114256;http://dx.doi.org/10.1128/JB.01180-06.
28. Amersdorfer P, Wong C, Chen S, Smith T, Deshpande S, Sheridan R, Finnern R, Marks JD. Molecular characterization of murine humoral immune response to botulinum neurotoxin type A binding domain as assessed by using phage antibody libraries. Infect Immun 1997; 65:3743-52; PMID:9284147.
29. nd, Lou J, Marks JD. Antibody protection against botulinum neurotoxin intoxication in mice. Infect Immun 2009; 77:4305-13; PMID:19651864;http://dx.doi.org/10.1128/IAI.00405-09.
30. Conway JO, Sherwood LJ, Collazo MT, Garza JA, Hayhurst A. Llama single domain antibodies specific for the 7 botulinum neurotoxin serotypes as heptaplex immunoreagents. PLoS ONE 2010; 5:e8818; PMID:20098614;http://dx.doi.org/10. 1371/journal.pone.0008818.
31. Dolimbek BZ, Aoki KR, Steward LE, Jankovic J, Atassi MZ. Mapping of the regions on the heavy chain of botulinum neurotoxin A (BoNT/A) recognized by antibodies of cervical dystonia patients with immunoresistance to BoNT/A. Mol Immunol 2007; 44:1029-41; PMID:16647121;http://dx.doi.org/10.1016/j.molimm.2006. 03.011.
32. Kalb SR, Lou J, Garcia-Rodriguez C, Geren IN, Smith TJ, Moura H, Marks JD, Smith LA, Pirkle JL, Barr JR. Extraction;inhibition of enzymatic activity of botulinum neurotoxins/A1, /A2,;/A3 by a panel of monoclonal anti-BoNT/A antibodies. PLoS ONE 2009; 4:e5355; PMID:19399171;http://dx.doi.org/10.1371/ journal.pone.0005355.
33. Kozaki S, Miki A, Kamata Y, Ogasawara J, Sakaguchi G. Immunological characterization of papain-induced fragments of Clostridium botulinum type A neurotoxin;interaction of the fragments with brain synaptosomes. Infect Immun 1989; 57:2634-9; PMID:2668181.
34. Nowakowski A, Wang C, Powers DB, Amersdorfer P, Smith TJ, Montgomery VA, Sheridan R, Blake R, Smith LA, Marks JD. Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody. Proc Natl Acad Sci USA 2002; 99:11346-50; PMID:12177434;http://dx.doi.org/10.1073/pnas.172229899.
35. Razai A, Garcia-Rodriguez C, Lou J, Geren IN, Forsyth CM, Robles Y, Tsai R, Smith TJ, Smith LA, Siegel RW, et al. Molecular evolution of antibody affinity for sensitive detection of botulinum neurotoxin type A. J Mol Biol 2005; 351:158-69; PMID:16002090 ;http://dx.doi.org/10.1016/j.jmb.2005.06.003.
36. Dong J, Thompson AA, Fan Y, Lou J, Conrad F, Ho M, Pires-Alves M, Wilson BA, Stevens RC, Marks JD. A single-domain llama antibody potently inhibits the enzymatic activity of botulinum neurotoxin by binding to the non-catalytic alphaexosite binding region. J Mol Biol 2010; 397:1106-18; PMID:20138889;http:// dx.doi.org/10.1016/j.jmb.2010.01.070.
37. Takahashi T, Joshi SG, Al-Saleem F, Ancharski D, Singh A, Nasser Z, Simpson LL. Localization of the sites;characterization of the mechanisms by which anti-light chain antibodies neutralize the actions of the botulinum holotoxin. Vaccine 2009; 27:2616-24; PMID:19428868;http://dx.doi.org/10.1016/j. vaccine.2009.02.051.
38. Rülker T, Voß L, Thullier P, O' Brien LM, Pelat T, Perkins SD, Langermann C, Schirrmann T, Dübel S, Marschall H-J, et al. Isolation;characterisation of a human-like antibody fragment (scFv) that inactivates VEEV in vitro;in vivo. PLoS ONE 2012; 7:e37242; PMID:22666347;http:/ /dx.doi.org/10.1371/journal.pone.0037242.
39. Rasetti-Escargueil C, Jones RGA, Liu Y, Sesardic D. Measurement of botulinum types A, B;E neurotoxicity using the phrenic nerve-hemidiaphragm: improved precision with in-bred mice. Toxicon 2009; 53:503-11; PMID:19673096;http://dx.doi.org/10.1016/j.toxicon.2009.01.019.
40. Rasetti-Escargueil C, Liu Y, Rigsby P, Jones RGA, Sesardic D. Phrenic nerve-hemidiaphragm as a highly sensitive replacement assay for determination of functional botulinum toxin antibodies. Toxicon 2011; 57:1008-16; PMID:21513727;http://dx.doi.org/10.1016/j.toxicon.2011.04.003.
41. Sheridan RE, Deshpande SS, Amersdorfer P, Marks JD, Smith T. Anomalous enhancement of botulinum toxin type A neurotoxicity in the presence of antitoxin. Toxicon 2001; 39:651-7; PMID:11072043;http://dx.doi.org/10.1016/ S0041-0101(00)00189-6.
42. Zdanovsky A, Zdanovsky D, Zdanovskaia M. Epitope mapping of botulinum neurotoxins light chains. Toxicon 2012; 60:1277-86; PMID:22922018;http://dx.doi. org/10.1016/j.toxicon.2012.08.002.
43. Hust M, Meyer T, Voedisch B, Rülker T, Thie H, El-Ghezal A, Kirsch MI, Schütte M, Helmsing S, Meier D, et al. A human scFv antibody generation pipeline for proteome research. J Biotechnol 2011; 152:159-70; PMID:20883731;http://dx.doi.org/10.1016/j.jbiotec.2010.09.945.
44. Pelat T, Thullier P. Non-human primate immune libraries combined with germline humanization: an (almost) new,;powerful approach for the isolation of therapeutic antibodies. MAbs 2009; 1:377-81; PMID:20068407;http://dx.doi.org/10. 4161/mabs.1.4.8635.
45. Pelat T, Bedouelle H, Rees AR, Crennell SJ, Lefranc M-P, Thullier P. Germline humanization of a nonhuman primate antibody that neutralizes the anthrax toxin, by in vitro;in silico engineering. J Mol Biol 2008; 384:1400-7; PMID:18976662;http://dx.doi.org/10.1016/j.jmb.2008.10.033.
46. Thullier P, Chahboun S, Pelat T. A comparison of human;macaque (Macaca mulatta) immunoglobulin germline V regions;its implications for antibody engineering. MAbs 2010; 2:528-38; PMID:20562531;http://dx.doi.org/10.4161/mabs. 2.5.12545.
47. USDA Animal Welfare Act (AWA). 7 U.S.C. 2131 et seq., as amended;Health Research Extension Act of 1985 ("'Animals in Research'"). 1985.
48. National Research Council. Guide for the Care;Use of Laboratory Animals. Eighth Edition. Washington: The National Academies Press; 2011.
49. Pelat T, Hust M, Thullier P. Obtention;engineering of non-human primate (NHP) antibodies for therapeutics. Mini Rev Med Chem 2009; 9:1633-8; PMID:20105119;http://dx.doi.org/10.2174/138955709791012283.
50. Schirrmann T, Meyer T, Schütte M, Frenzel A, Hust M. Phage display for the generation of antibodies for proteome research, diagnostics;therapy. Molecules 2011; 16:412-26; PMID:21221060;http://dx.doi.org/10.3390/ molecules16010412.
51. Rondot S, Koch J, Breitling F, Dübel S. A helper phage to improve single-chain antibody presentation in phage display. Nat Biotechnol 2001; 19:75-8; PMID:11135557;http://dx.doi.org/10.1038/83567.
52. Soltes G, Hust M, Ng KKY, Bansal A, Field J, Stewart DIH, Dübel S, Cha S, Wiersma EJ. On the influence of vector design on antibody phage display. J Biotechnol 2007; 127:626-37; PMID:16996161;http://dx.doi.org/10.1016/j. jbiotec.2006.08.015.
53. Schuck P, Minton AP. Kinetic analysis of biosensor data: elementary tests for self-consistency. Trends Biochem Sci 1996; 21:458-60; PMID:9009825;http:// dx.doi.org/10.1016/S0968-0004(96)20025-8.
54. Jones RGA, Ochiai M, Liu Y, Ekong T, Sesardic D. Development of improved SNAP25 endopeptidase immuno-assays for botulinum type A;E toxins. J Immunol Methods 2008; 329:92-101; PMID:17976638;http://dx.doi.org/10.1016/j.jim.2007.09. 014.
55. Frank R. Spot-Synthesis: An easy technique for the positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron 1992; 48:9217-32; http://dx.doi.org/10.1016/S0040-4020(01)85612-X.
56. Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC. Crystal structure of botulinum neurotoxin type A;implications for toxicity. Nat Struct Biol 1998; 5:898-902; PMID:9783750;http://dx.doi.org/10.1038/2338.