Monoclonal Antibodies and Antibody Like Fragments Derived from Immunised Phage Display Libraries

  • Obinna Ubah
  • Soumya PalliyilEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1053)


Morbidity and mortality associated with infectious diseases are always on the rise, especially in poorer countries and in the aging population. The inevitable, but unpredictable emergence of new infectious diseases has become a global threat. HIV/AIDS, severe acute respiratory syndrome (SARS), and the more recent H1N1 influenza are only a few of the numerous examples of emerging infectious diseases in the modern era. However despite advances in diagnostics, therapeutics and vaccines, there is need for more specific, efficacious, cost-effective and less toxic treatment and preventive drugs. In this chapter, we discuss a powerful combinatorial technology in association with animal immunisation that is capable of generating biologic drugs with high affinity, efficacy and limited off-site toxicity, and diagnostic tools with great precision. Although time consuming, immunisation still remains the preferred route for the isolation of high-affinity antibodies and antibody-like fragments. Phage display is a molecular diversity technology that allows the presentation of large peptide and protein libraries on the surface of filamentous phage. The selection of binding fragments from phage display libraries has proven significant for routine isolation of invaluable peptides, antibodies, and antibody-like domains for diagnostic and therapeutic applications. Here we highlight the many benefits of combining immunisation with phage display in combating infectious diseases, and how our knowledge of antibody engineering has played a crucial role in fully exploiting these platforms in generating therapeutic and diagnostic biologics towards antigenic targets of infectious organisms.


Monoclonal antibodies Phage display Immunisation Combinatorial technology Infectious diseases Diagnostic Therapeutic 


  1. 1.
    Akiyama M, Oishi K, Tao M, Matsumoto K, Pollack M (2000) Antibacterial properties of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide-specific monoclonal antibody (MAb) in a murine thigh infection model: combined effects of MAb and ceftazidime. Microbiol Immunol 44(8):629–635PubMedCrossRefGoogle Scholar
  2. 2.
    Al Qaraghuli MM, Palliyil S, Broadbent G, Cullen DC, Charlton KA, Porter AJ (2015) Defining the complementarities between antibodies and haptens to refine our understanding and aid the prediction of a successful binding interaction. BMC Biotechnol 15(1):99PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Alzogaray V, Danquah W, Aguirre A, Urrutia M, Berguer P, Véscovi EG, Haag F, Koch-Nolte F, Goldbaum FA (2011) Single-domain llama antibodies as specific intracellular inhibitors of SpvB, the actin ADP-ribosylating toxin of Salmonella typhimurium. FASEB J 25(2):526–534PubMedCrossRefGoogle Scholar
  4. 4.
    Amersdorfer P, Wong C, Smith T, Chen S, Deshpande S, Sheridan R, Marks JD (2002) Genetic and immunological comparison of anti-botulinum type A antibodies from immune and non-immune human phage libraries. Vaccine 20(11):1640–1648PubMedCrossRefGoogle Scholar
  5. 5.
    Bakherad H, Gargari SLM, Rasooli I, RajabiBazl M, Mohammadi M, Ebrahimizadeh W, Ardakani LS, Zare H (2013) In vivo neutralization of botulinum neurotoxins serotype E with heavy-chain camelid antibodies (VHH). Mol Biotechnol 55(2):159–167PubMedCrossRefGoogle Scholar
  6. 6.
    Barelle C, Gill DS, Charlton K (2009) Shark novel antigen receptors—the next generation of biologic therapeutics? In: Pharmaceutical biotechnology. Springer, New York, pp 49–62CrossRefGoogle Scholar
  7. 7.
    Barry JD, McCulloch R (2001) Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Adv Parasitol 49:1–70PubMedCrossRefGoogle Scholar
  8. 8.
    Beerli RR, Rader C (2010) Mining human antibody repertoires. MAbs/Taylor & FrancisGoogle Scholar
  9. 9.
    Bradbury AR, Sidhu S, Dübel S, McCafferty J (2011) Beyond natural antibodies: the power of in vitro display technologies. Nat Biotechnol 29(3):245–254PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC (2012) Hidden killers: human fungal infections. Sci Transl Med 4(165):165rv113CrossRefGoogle Scholar
  11. 11.
    Browne SH, Hasegawa P, Okamoto S, Fierer J, Guiney DG (2008) Identification of Salmonella SPI-2 secretion system components required for SpvB-mediated cytotoxicity in macrophages and virulence in mice. FEMS Immunol Med Microbiol 52(2):194–201PubMedCrossRefGoogle Scholar
  12. 12.
    Burnie JP, Matthews RC, Carter T, Beaulieu E, Donohoe M, Chapman C, Williamson P, Hodgetts SJ (2000) Identification of an Immunodominant ABC transporter in Methicillin-resistant Staphylococcus aureus infections. Infect Immun 68(6):3200–3209PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Burton DR, Barbas CF, Persson M, Koenig S, Chanock RM, Lerner RA (1991) A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc Natl Acad Sci 88(22):10134–10137PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Cabezas S, Rojas G, Pavon A, Bernardo L, Castellanos Y, Alvarez M, Pupo M, Guillen G, Guzman MG (2009) Phage-displayed antibody fragments recognizing dengue 3 and dengue 4 viruses as tools for viral serotyping in sera from infected individuals. Arch Virol 154(7):1035PubMedCrossRefGoogle Scholar
  15. 15.
    Cao J, Sun Y-q, Berglindh T, Mellgård B, Li Z-q, Mårdh B, Mårdh S (2000) Helicobacter pylori-antigen-binding fragments expressed on the filamentous M13 phage prevent bacterial growth. Biochim Biophys Acta (BBA) Gen Subj 1474(1):107–113CrossRefGoogle Scholar
  16. 16.
    Chahboun S, Hust M, Liu Y, Pelat T, Miethe S, Helmsing S, Jones RG, Sesardic D, Thullier P (2011) 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 11(1):113PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Charlton K, Harris W, Porter A (2001) The isolation of super-sensitive anti-hapten antibodies from combinatorial antibody libraries derived from sheep. Biosens Bioelectron 16(9):639–646PubMedCrossRefGoogle Scholar
  18. 18.
    Chassagne S, Laffly E, Drouet E, Hérodin F, Lefranc M-P, Thullier P (2004) A high-affinity macaque antibody Fab with human-like framework regions obtained from a small phage display immune library. Mol Immunol 41(5):539–546PubMedCrossRefGoogle Scholar
  19. 19.
    Chaturvedi AK, Kavishwar A, Keshava GS, Shukla P (2005) Monoclonal immunoglobulin G1 directed against Aspergillus fumigatus cell wall glycoprotein protects against experimental murine aspergillosis. Clin Diagn Lab Immunol 12(9):1063–1068PubMedPubMedCentralGoogle Scholar
  20. 20.
    Chen Z, Earl P, Americo J, Damon I, Smith SK, Zhou Y-H, Yu F, Sebrell A, Emerson S, Cohen G (2006a) Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus. Proc Natl Acad Sci U S A 103(6):1882–1887PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Chen Z, Moayeri M, Zhou Y-H, Leppla S, Emerson S, Sebrell A, Yu F, Svitel J, Schuck P, Claire MS (2006b) Efficient neutralization of anthrax toxin by chimpanzee monoclonal antibodies against protective antigen. J Infect Dis 193(5):625–633PubMedCrossRefGoogle Scholar
  22. 22.
    Chen Z, Moayeri M, Crown D, Emerson S, Gorshkova I, Schuck P, Leppla SH, Purcell RH (2009a) Novel chimpanzee/human monoclonal antibodies that neutralize anthrax lethal factor, and evidence for possible synergy with anti-protective antigen antibody. Infect Immun 77(9):3902–3908PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Chen Z, Moayeri M, Zhao H, Crown D, Leppla SH, Purcell RH (2009b) Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding. Proc Natl Acad Sci 106(32):13487–13492PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Conrath KE, Lauwereys M, Galleni M, Matagne A, Frère J-M, Kinne J, Wyns L, Muyldermans S (2001) β-Lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae. Antimicrob Agents Chemother 45(10):2807–2812PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Corda D, Di Girolamo M (2003) Functional aspects of protein mono-ADP-ribosylation. EMBO J 22(9):1953–1958PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Cordero RJ, Pontes B, Frases S, Nakouzi AS, Nimrichter L, Rodrigues ML, Viana NB, Casadevall A (2013) Antibody binding to Cryptococcus neoformans impairs budding by altering capsular mechanical properties. J Immunol 190(1):317–323PubMedCrossRefGoogle Scholar
  27. 27.
    Daffis S, Kontermann RE, Korimbocus J, Zeller H, Klenk H-D, ter Meulen J (2005) Antibody responses against wild-type yellow fever virus and the 17D vaccine strain: characterization with human monoclonal antibody fragments and neutralization escape variants. Virology 337(2):262–272PubMedCrossRefGoogle Scholar
  28. 28.
    Detalle L, Stohr T, Palomo C, Piedra PA, Gilbert BE, Mas V, Millar A, Power UF, Stortelers C, Allosery K (2016) Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection. Antimicrob Agents Chemother 60(1):6–13PubMedCrossRefGoogle Scholar
  29. 29.
    Druar C, Saini SS, Cossitt MA, Yu F, Qiu X, Geisbert TW, Jones S, Jahrling PB, Stewart DI, Wiersma EJ (2005) Analysis of the expressed heavy chain variable-region genes of Macaca fascicularis and isolation of monoclonal antibodies specific for the Ebola virus’ soluble glycoprotein. Immunogenetics 57(10):730–738PubMedCrossRefGoogle Scholar
  30. 30.
    Duan J, Yan X, Guo X, Cao W, Han W, Qi C, Feng J, Yang D, Gao G, Jin G (2005) A human SARS-CoV neutralizing antibody against epitope on S2 protein. Biochem Biophys Res Commun 333(1):186–193PubMedCrossRefGoogle Scholar
  31. 31.
    Ehrlich PH, Moustafa ZA, Harfeldt KE, Isaacson C, Östberg L (1990) Potential of primate monoclonal antibodies to substitute for human antibodies: nucleotide sequence of chimpanzee Fab fragments. Hum Antibodies 1(1):23–26Google Scholar
  32. 32.
    Forsman A, Beirnaert E, Aasa-Chapman MM, Hoorelbeke B, Hijazi K, Koh W, Tack V, Szynol A, Kelly C, McKnight A (2008) Llama antibody fragments with cross-subtype human immunodeficiency virus type 1 (HIV-1)-neutralizing properties and high affinity for HIV-1 gp120. J Virol 82(24):12069–12081PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Fu Y-Y, Li Z-G, Yang Y-W, Deng W, Duan W, Miao Q, Wang Z-K, Xia Y-X (2009) Isolation of single chain variable fragments against six esters of pyrethrins by subtractive phage display. Biosci Biotechnol Biochem 73(7):1541–1549PubMedCrossRefGoogle Scholar
  34. 34.
    Gassmann M, Thömmes P, Weiser T, Hübscher U (1990) Efficient production of chicken egg yolk antibodies against a conserved mammalian protein. FASEB J 4(8):2528–2532PubMedCrossRefGoogle Scholar
  35. 35.
    Geng X, Kong X, Hu H, Chen J, Yang F, Liang H, Chen X, Hu Y (2015) Research and development of therapeutic mAbs: an analysis based on pipeline projects. Hum Vaccin Immunother 11(12):2769–2776PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Gigliotti F, Haidaris CG, Wright TW, Harmsen AG (2002) Passive intranasal monoclonal antibody prophylaxis against murine Pneumocystis carinii pneumonia. Infect Immun 70(3):1069–1074PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Greenberg AS, Avila D, Hughes M, Hughes A (1995) A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks. Nature 374(6518):168PubMedCrossRefGoogle Scholar
  38. 38.
    Haidaris CG, Malone J, Sherrill LA, Bliss JM, Gaspari AA, Insel RA, Sullivan MA (2001) Recombinant human antibody single chain variable fragments reactive with Candida albicans surface antigens. J Immunol Methods 257(1):185–202PubMedCrossRefGoogle Scholar
  39. 39.
    Han Y (2010) Efficacy of combination immunotherapy of IgM MAb B6. 1 and amphotericin B against disseminated candidiasis. Int Immunopharmacol 10(12):1526–1531PubMedCrossRefGoogle Scholar
  40. 40.
    Han Y, Riesselman MH, Cutler JE (2000) Protection against candidiasis by an immunoglobulin G3 (IgG3) monoclonal antibody specific for the same mannotriose as an IgM protective antibody. Infect Immun 68(3):1649–1654PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Hayhurst A, Happe S, Mabry R, Koch Z, Iverson BL, Georgiou G (2003) Isolation and expression of recombinant antibody fragments to the biological warfare pathogen Brucella melitensis. J Immunol Methods 276(1):185–196PubMedCrossRefGoogle Scholar
  42. 42.
    Hof D, Hoeke M, Raats J (2008) Multiple-antigen immunization of chickens facilitates the generation of recombinant antibodies to autoantigens. Clin Exp Immunol 151(2):367–377PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Hoogenboom HR (2002) Overview of antibody phage-display technology and its applications. In: Antibody phage display: methods and protocols, pp 1–37Google Scholar
  44. 44.
    Hülseweh B, Rülker T, Pelat T, Langermann C, Frenzel A, Schirrmann T, Dübel S, Thullier P, Hust M (2014) Human-like antibodies neutralizing western equine encephalitis virus. MAbs/Taylor & FrancisGoogle Scholar
  45. 45.
    Hultberg A, Temperton NJ, Rosseels V, Koenders M, Gonzalez-Pajuelo M, Schepens B, Ibañez LI, Vanlandschoot P, Schillemans J, Saunders M (2011) Llama-derived single domain antibodies to build multivalent, superpotent and broadened neutralizing anti-viral molecules. PLoS One 6(4):e17665PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Ibañez LI, De Filette M, Hultberg A, Verrips T, Temperton N, Weiss RA, Vandevelde W, Schepens B, Vanlandschoot P, Saelens X (2011) Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. J Infect Dis 203(8):1063–1072PubMedCrossRefGoogle Scholar
  47. 47.
    Jähnichen S, Blanchetot C, Maussang D, Gonzalez-Pajuelo M, Chow KY, Bosch L, De Vrieze S, Serruys B, Ulrichts H, Vandevelde W (2010) CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells. Proc Natl Acad Sci 107(47):20565–20570PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    James K, Bell GT (1987) Human monoclonal antibody production: current status and future prospects. J Immunol Methods 100(1–2):5–40PubMedCrossRefGoogle Scholar
  49. 49.
    Jangra P, Singh A (2010) Staphylococcus aureus β-hemolysin-neutralizing single-domain antibody isolated from phage display library of Indian desert camel. Asian Pac J Trop Med 3(1):1–7CrossRefGoogle Scholar
  50. 50.
    Kaufmann GF, Sartorio R, Lee S-H, Mee JM, Altobell LJ, Kujawa DP, Jeffries E, Clapham B, Meijler MM, Janda KD (2006) Antibody interference with N-acyl homoserine lactone-mediated bacterial quorum sensing. J Am Chem Soc 128(9):2802–2803PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Koch-Nolte F, Kernstock S, Mueller-Dieckmann C, Weiss MS, Haag F (2008) Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases. Front Biosci 13:6716–6729PubMedCrossRefGoogle Scholar
  52. 52.
    Koh WW, Steffensen S, Gonzalez-Pajuelo M, Hoorelbeke B, Gorlani A, Szynol A, Forsman A, Aasa-Chapman MM, de Haard H, Verrips T (2010) Generation of a family-specific phage library of llama single chain antibody fragments that neutralize HIV-1. J Biol Chem 285(25):19116–19124PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Kovaleva M, Ferguson L, Steven J, Porter A, Barelle C (2014) Shark variable new antigen receptor biologics–a novel technology platform for therapeutic drug development. Expert Opin Biol Ther 14(10):1527–1539PubMedCrossRefGoogle Scholar
  54. 54.
    Kramer RA, Marissen WE, Goudsmit J, Visser TJ, Bakker AQ, de Jong M, Jongeneelen M, Thijsse S, Backus HH, Rice AB (2005) The human antibody repertoire specific for rabies virus glycoprotein as selected from immune libraries. Eur J Immunol 35(7):2131–2145PubMedCrossRefGoogle Scholar
  55. 55.
    Krishnaswamy S, Kabir ME, Rahman MM, Miyamoto M, Furuichi Y, Komiyama T (2011) Isolation and characterization of recombinant single chain fragment variable anti-idiotypic antibody specific to Aspergillus fumigatus membrane protein. J Immunol Methods 366(1):60–68PubMedCrossRefGoogle Scholar
  56. 56.
    Laffly E, Danjou L, Condemine F, Vidal D, Drouet E, Lefranc M-P, Bottex C, Thullier P (2005) Selection of a macaque Fab with framework regions like those in humans, high affinity, and ability to neutralize the protective antigen (PA) of Bacillus anthracis by binding to the segment of PA between residues 686 and 694. Antimicrob Agents Chemother 49(8):3414–3420PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Larsen RA, Pappas PG, Perfect J, Aberg JA, Casadevall A, Cloud GA, James R, Filler S, Dismukes WE (2005) Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother 49(3):952–958PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Laventie B-J, Rademaker HJ, Saleh M, de Boer E, Janssens R, Bourcier T, Subilia A, Marcellin L, van Haperen R, Lebbink JH (2011) Heavy chain-only antibodies and tetravalent bispecific antibody neutralizing Staphylococcus aureus leukotoxins. Proc Natl Acad Sci 108(39):16404–16409PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Lee J-H, Jang E-C, Han Y (2011) Combination immunotherapy of MAb B6. 1 with fluconazole augments therapeutic effect to disseminated candidiasis. Arch Pharm Res 34(3):399PubMedCrossRefGoogle Scholar
  60. 60.
    Lesnick ML, Guiney DG (2001) The best defense is a good offense–Salmonella deploys an ADP-ribosylating toxin. Trends Microbiol 9(1):2–4PubMedCrossRefGoogle Scholar
  61. 61.
    Lesnick ML, Reiner NE, Fierer J, Guiney DG (2001) The Salmonella spvB virulence gene encodes an enzyme that ADP-ribosylates actin and destabilizes the cytoskeleton of eukaryotic cells. Mol Microbiol 39(6):1464–1470PubMedCrossRefGoogle Scholar
  62. 62.
    Li Y, Kilpatrick J, Whitelam GC (2000) Sheep monoclonal antibody fragments generated using a phage display system. J Immunol Methods 236(1):133–146PubMedCrossRefGoogle Scholar
  63. 63.
    Margarit SM, Davidson W, Frego L, Stebbins CE (2006) A steric antagonism of actin polymerization by a salmonella virulence protein. Structure 14(8):1219–1229PubMedCrossRefGoogle Scholar
  64. 64.
    Mascola JR, Haynes BF (2013) HIV-1 neutralizing antibodies: understanding nature’s pathways. Immunol Rev 254(1):225–244PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Mazur NI, Martinón-Torres F, Baraldi E, Fauroux B, Greenough A, Heikkinen T, Manzoni P, Mejias A, Nair H, Papadopoulos NG (2015) Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics. Lancet Respir Med 3(11):888–900PubMedCrossRefGoogle Scholar
  66. 66.
    Meissner F, Maruyama T, Frentsch M, Hessell AJ, Rodriguez LL, Geisbert TW, Jahrling PB, Burton DR, Parren PW (2002) Detection of antibodies against the four subtypes of Ebola virus in sera from any species using a novel antibody-phage indicator assay. Virology 300(2):236–243PubMedCrossRefGoogle Scholar
  67. 67.
    Mejias A, Garcia-Maurino C, Rodriguez-Fernandez R, Peeples ME, Ramilo O (2017) Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection. Vaccine 35(3):496–502PubMedCrossRefGoogle Scholar
  68. 68.
    Menzel S, Rissiek B, Haag F, Goldbaum FA, Koch-Nolte F (2013) The art of blocking ADP-ribosyltransferases (ARTs): nanobodies as experimental and therapeutic tools to block mammalian and toxin ARTs. FEBS J 280(15):3543–3550PubMedCrossRefGoogle Scholar
  69. 69.
    Mohammadzadeh S, Rajabibazl M, Fourozandeh M, Rasaee MJ, Rahbarizadeh F, Mohammadi M (2014) Production of recombinant scFv against p24 of human immunodeficiency virus type 1 by phage display technology. Monoclon Antibodies Immunodiagn Immunother 33(1):28–33CrossRefGoogle Scholar
  70. 70.
    Moragues MD, Omaetxebarria MJ, Elguezabal N, Sevilla MJ, Conti S, Polonelli L, Pontón J (2003) A monoclonal antibody directed against a Candida albicans cell wall mannoprotein exerts three anti-C. albicans activities. Infect Immun 71(9):5273–5279PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Muyldermans S (2013) Nanobodies: natural single-domain antibodies. Annu Rev Biochem 82:775–797PubMedCrossRefGoogle Scholar
  72. 72.
    Muyldermans S, Wyns L (2007) Antibody molecules which interact specifically with the active site or cleft of a target molecule. Google PatentsGoogle Scholar
  73. 73.
    Nagao M (2013) A multicentre analysis of epidemiology of the nosocomial bloodstream infections in Japanese university hospitals. Clin Microbiol Infect 19(9):852–858PubMedCrossRefGoogle Scholar
  74. 74.
    Nowakowski A, Wang C, Powers D, Amersdorfer P, Smith T, Montgomery V, Sheridan R, Blake R, Smith L, Marks J (2002) Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody. Proc Natl Acad Sci 99(17):11346–11350PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Ogata N, Ostberg L, Ehrlich PH, Wong DC, Miller RH, Purcell RH (1993) Markedly prolonged incubation period of hepatitis B in a chimpanzee passively immunized with a human monoclonal antibody to the a determinant of hepatitis B surface antigen. Proc Natl Acad Sci 90(7):3014–3018PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Okada J, Ohshima N, Kubota-Koketsu R, Ota S, Takase W, Azuma M, Iba Y, Nakagawa N, Yoshikawa T, Nakajima Y (2010) Monoclonal antibodies in man that neutralized H3N2 influenza viruses were classified into three groups with distinct strain specificity: 1968–1973, 1977–1993 and 1997–2003. Virology 397(2):322–330PubMedCrossRefGoogle Scholar
  77. 77.
    Oleksiewicz MB, Nagy G, Nagy E (2012) Anti-bacterial monoclonal antibodies: back to the future? Arch Biochem Biophys 526(2):124–131PubMedCrossRefGoogle Scholar
  78. 78.
    Palliyil S, Downham C, Broadbent I, Charlton K, Porter AJ (2014) High-sensitivity monoclonal antibodies specific for homoserine lactones protect mice from lethal Pseudomonas aeruginosa infections. Appl Environ Microbiol 80(2):462–469PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Pant N, Hultberg A, Zhao Y, Svensson L, Pan-Hammarström Q, Johansen K, Pouwels PH, Ruggeri FM, Hermans P, Frenken L (2006) Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea. J Infect Dis 194(11):1580–1588PubMedCrossRefGoogle Scholar
  80. 80.
    Pelat T, Hust M, Laffly E, Condemine F, Bottex C, Vidal D, Lefranc M-P, Dübel S, Thullier P (2007) High-affinity, 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 51(8):2758–2764PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Pereira SS, Moreira-Dill LS, Morais MS, Prado ND, Barros ML, Koishi AC, Mazarrotto GA, Gonçalves GM, Zuliani JP, Calderon LA (2014) Novel camelid antibody fragments targeting recombinant nucleoprotein of Araucaria hantavirus: a prototype for an early diagnosis of Hantavirus Pulmonary Syndrome. PLoS One 9(9):e108067PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Rachini A, Pietrella D, Lupo P, Torosantucci A, Chiani P, Bromuro C, Proietti C, Bistoni F, Cassone A, Vecchiarelli A (2007) An anti-β-glucan monoclonal antibody inhibits growth and capsule formation of Cryptococcus neoformans in vitro and exerts therapeutic, anticryptococcal activity in vivo. Infect Immun 75(11):5085–5094PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Reichert JM (2016) Antibodies to watch in 2016. MAbs/Taylor & FrancisGoogle Scholar
  84. 84.
    Reynaud C-A, Dufour V, Weill J-C (1997) Generation of diversity in mammalian gut-associated lymphoid tissues: restricted V gene usage does not preclude complex V gene organization. J Immunol 159(7):3093–3095PubMedGoogle Scholar
  85. 85.
    Rodrigues ML, Shi L, Barreto-Bergter E, Nimrichter L, Farias SE, Rodrigues EG, Travassos LR, Nosanchuk JD (2007) Monoclonal antibody to fungal glucosylceramide protects mice against lethal Cryptococcus neoformans infection. Clin Vaccine Immunol 14(10):1372–1376PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Roopenian DC, Akilesh S (2007) FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7(9):715PubMedCrossRefGoogle Scholar
  87. 87.
    Rosas ÁL, Nosanchuk JD, Casadevall A (2001) Passive immunization with melanin-binding monoclonal antibodies prolongs survival of mice with lethal Cryptococcus neoformans infection. Infect Immun 69(5):3410–3412PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Sabarth N, Hurvitz R, Schmidt M, Zimny-Arndt U, Jungblut PR, Meyer TF, Bumann D (2005) Identification of Helicobacter pylori surface proteins by selective proteinase K digestion and antibody phage display. J Microbiol Methods 62(3):345–349PubMedCrossRefGoogle Scholar
  89. 89.
    Sanna PP, Williamson RA, De Logu A, Bloom FE, Burton DR (1995) Directed selection of recombinant human monoclonal antibodies to herpes simplex virus glycoproteins from phage display libraries. Proc Natl Acad Sci 92(14):6439–6443PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Saylor C, Dadachova E, Casadevall A (2009) Monoclonal antibody-based therapies for microbial diseases. Vaccine 27:G38–G46PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Schofield D, Glamann J, Emerson S, Purcell R (2000) Identification by phage display and characterization of two neutralizing chimpanzee monoclonal antibodies to the hepatitis E virus capsid protein. J Virol 74(12):5548–5555PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Schofield D, Satterfield W, Emerson S, Purcell R (2002) Four chimpanzee monoclonal antibodies isolated by phage display neutralize hepatitis A virus. Virology 292(1):127–136PubMedCrossRefGoogle Scholar
  93. 93.
    Selvakumar D, Miyamoto M, Furuichi Y, Komiyama T (2006) Inhibition of fungal β-1, 3-glucan synthase and cell growth by HM-1 killer toxin single-chain anti-idiotypic antibodies. Antimicrob Agents Chemother 50(9):3090–3097PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Serruys B, Van Houtte F, Verbrugghe P, Leroux-Roels G, Vanlandschoot P (2009) Llama-derived single-domain intrabodies inhibit secretion of hepatitis B virions in mice. Hepatology 49(1):39–49PubMedCrossRefGoogle Scholar
  95. 95.
    Serruys B, Van Houtte F, Farhoudi-Moghadam A, Leroux-Roels G, Vanlandschoot P (2010) Production, characterization and in vitro testing of HBcAg-specific VHH intrabodies. J Gen Virol 91(3):643–652PubMedCrossRefGoogle Scholar
  96. 96.
    Stijlemans B, Caljon G, Natesan SKA, Saerens D, Conrath K, Pérez-Morga D, Skepper JN, Nikolaou A, Brys L, Pays E (2011) High affinity nanobodies against the Trypanosome brucei VSG are potent trypanolytic agents that block endocytosis. PLoS Pathog 7(6):e1002072PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Szynol A, De Haard J, Veerman E, De Soet J, van Nieuw Amerongen A (2006) Design of a peptibody consisting of the antimicrobial peptide dhvar5 and a llama variable heavy-chain antibody fragment. Chem Biol Drug Des 67(6):425–431PubMedCrossRefGoogle Scholar
  98. 98.
    Tabares-da Rosa S, Rossotti M, Carleiza C, Carrión F, Pritsch O, Ahn KC, Last JA, Hammock BD, González-Sapienza G (2011) Competitive selection from single domain antibody libraries allows isolation of high-affinity antihapten antibodies that are not favored in the llama immune response. Anal Chem 83(18):7213–7220PubMedCrossRefGoogle Scholar
  99. 99.
    Tan M-W, Mahajan-Miklos S, Ausubel FM (1999) Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci 96(2):715–720PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Throsby M, van den Brink E, Jongeneelen M, Poon LL, Alard P, Cornelissen L, Bakker A, Cox F, van Deventer E, Guan Y (2008) Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS One 3(12):e3942PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Tremblay JM, Kuo C-L, Abeijon C, Sepulveda J, Oyler G, Hu X, Jin MM, Shoemaker CB (2010) Camelid single domain antibodies (VHHs) as neuronal cell intrabody binding agents and inhibitors of Clostridium botulinum neurotoxin (BoNT) proteases. Toxicon 56(6):990–998PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Unkauf T, Miethe S, Fühner V, Schirrmann T, Frenzel A, Hust M (2016) Generation of recombinant antibodies against toxins and viruses by phage display for diagnostics and therapy. In: Protein targeting compounds. Springer, Cham, pp 55–76Google Scholar
  103. 103.
    Van der Vaart J, Pant N, Wolvers D, Bezemer S, Hermans P, Bellamy K, Sarker S, Van der Logt C, Svensson L, Verrips C (2006) Reduction in morbidity of rotavirus induced diarrhoea in mice by yeast produced monovalent llama-derived antibody fragments. Vaccine 24(19):4130–4137PubMedCrossRefGoogle Scholar
  104. 104.
    Vincent J-L, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302(21):2323–2329PubMedCrossRefGoogle Scholar
  105. 105.
    Vogt MR, Moesker B, Goudsmit J, Jongeneelen M, Austin SK, Oliphant T, Nelson S, Pierson TC, Wilschut J, Throsby M (2009) Human monoclonal antibodies against West Nile virus induced by natural infection neutralize at a postattachment step. J Virol 83(13):6494–6507PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Watson D (1992) Biological half-life of ovine antibody in neonatal lambs and adult sheep following passive immunization. Vet Immunol Immunopathol 30(2–3):221–232PubMedCrossRefGoogle Scholar
  107. 107.
    Wild MA, Hong X, Maruyama T, Nolan MJ, Calveley PM, Malone JD, Wallace MR, Bowdish KS (2003) Human antibodies from immunized donors are protective against anthrax toxin in vivo. Nat Biotechnol 21(11):1305PubMedCrossRefGoogle Scholar
  108. 108.
    Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR (1994) Making antibodies by phage display technology. Annu Rev Immunol 12(1):433–455PubMedCrossRefGoogle Scholar
  109. 109.
    Woolley JA, Landon J (1995) Comparison of antibody production to human interleukin-6 (IL-6) by sheep and chickens. J Immunol Methods 178(2):253–265PubMedCrossRefGoogle Scholar
  110. 110.
    Zak O, O’Reilly T (1991) Animal models in the evaluation of antimicrobial agents. Antimicrob Agents Chemother 35(8):1527PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Zebedee SL, Barbas CF, Hom Y-L, Caothien R, Graff R, DeGraw J, Pyati J, LaPolla R, Burton DR, Lerner RA (1992) Human combinatorial antibody libraries to hepatitis B surface antigen. Proc Natl Acad Sci 89(8):3175–3179PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Zhang M-Y, Shu Y, Phogat S, Xiao X, Cham F, Bouma P, Choudhary A, Feng Y-R, Sanz I, Rybak S (2003) Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by sequential antigen panning of a phage display library. J Immunol Methods 283(1):17–25PubMedCrossRefGoogle Scholar
  113. 113.
    Zhang MX, Bohlman MC, Itatani C, Burton DR, Parren PW, Jeor SCS, Kozel TR (2006) Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice. Infect Immun 74(1):362–369PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Scottish Biologics FacilityElasmogen LtdAberdeenUK
  2. 2.Scottish Biologics FacilityUniversity of AberdeenAberdeenUK

Personalised recommendations