Skip to main content
SpringerLink
Log in

Anti-bacterial Monoclonal Antibodies

  • Chapter
  • First Online:
Recombinant Antibodies for Infectious Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1053))

Abstract

The failing efficacy of antibiotics and the high mortality rate among high-risk patients calls for new treatment modalities for bacterial infections. Due to the vastly divergent pathogenesis of human pathogens, each microbe requires a tailored approach. The main modes of action of anti-bacterial antibodies are virulence factor neutralization, complement-mediated bacterial lysis and enhancement of opsonophagocytic uptake and killing (OPK). Gram-positive bacteria cannot be lysed by complement and their pathogenesis often involves secreted toxins, therefore typically toxin-neutralization and OPK activity are required to prevent and ameliorate disease. In fact, the success stories in terms of approved products, in the anti-bacterial mAb field are based on toxin neutralization (Bacillus anthracis, Clostridium difficile). In contrast, Gram-negative bacteria are vulnerable to antibody-dependent complement-mediated lysis, while their pathogenesis rarely relies on secreted exotoxins, and involves the pro-inflammatory endotoxin (lipopolysaccharide). Given the complexity of bacterial pathogenesis, antibody therapeutics are expected to be most efficient upon targeting more than one virulence factor and/or combining different modes of action. The improved understanding of bacterial pathogenesis combined with the versatility and maturity of antibody discovery technologies available today are pivotal for the design of novel anti-bacterial therapeutics. The intensified research generating promising proof-of-concept data, and the increasing number of clinical programs with anti-bacterial mAbs, indicate that the field is ready to fulfill its promise in the coming years.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 189.00
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abboud N, Chow S-K, Saylor C, Janda A, Ravetch JV, Scharff MD, Casadevall A (2010) A requirement for FcγR in antibody-mediated bacterial toxin neutralization. J Exp Med 207(11):2395–2405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Almagro JC, Hernández I, Ramírez MC, Vargas-Madrazo E (1998) Structural differences between the repertoires of mouse and human germline genes and their evolutionary implications. Immunogenetics 47(5):355–363

    Article  CAS  PubMed  Google Scholar 

  3. Anderson AS, Miller AA, Donald RG, Scully IL, Nanra JS, Cooper D, Jansen KU (2012a) Development of a multicomponent Staphylococcus aureus vaccine designed to counter multiple bacterial virulence factors. Hum Vaccin Immunother 8(11):1585–1594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Anderson AS, Scully IL, Timofeyeva Y, Murphy E, McNeil LK, Mininni T, Nuñez L, Carriere M, Singer C, Dilts DA (2012b) Staphylococcus aureus manganese transport protein C is a highly conserved cell surface protein that elicits protective immunity against S. aureus and Staphylococcus epidermidis. J Infect Dis 205(11):1688–1696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Apicella MA, Post DM, Fowler AC, Jones BD, Rasmussen JA, Hunt JR, Imagawa S, Choudhury B, Inzana TJ, Maier TM (2010) Identification, characterization and immunogenicity of an O-antigen capsular polysaccharide of Francisella tularensis. PLoS One 5(7):e11060

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Aribam SD, Harada T, Elsheimer-Matulova M, Iwata T, Kanehira K, Hikono H, Matsui H, Ogawa Y, Shimoji Y, Eguchi M (2016) Specific monoclonal antibody overcomes the Salmonella enterica erovar Typhimurium’s adaptive mechanisms of ntramacrophage survival and replication. PLoS One 11(3):e0151352

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Babcock GJ, Broering TJ, Hernandez HJ, Mandell RB, Donahue K, Boatright N, Stack AM, Lowy I, Graziano R, Molrine D (2006) Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters. Infect Immun 74(11):6339–6347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Badarau A, Rouha H, Malafa S, Logan DT, Håkansson M, Stulik L, Dolezilkova I, Teubenbacher A, Gross K, Maierhofer B (2015) Structure-function analysis of heterodimer formation, oligomerization, and receptor binding of the Staphylococcus aureus bi-component toxin LukGH. J Biol Chem 290(1):142–156

    Article  CAS  PubMed  Google Scholar 

  9. Badarau A, Rouha H, Malafa S, Battles MB, Walker L, Nielson N, Dolezilkova I, Teubenbacher A, Banerjee S, Maierhofer B (2016) Context matters: the importance of dimerization-induced conformation of the LukGH leukocidin of Staphylococcus aureus for the generation of neutralizing antibodies. MAbs, Taylor & Francis

    Google Scholar 

  10. Badarau A, Trstenjak N, Nagy E (2017) Structure and function of the two-component cytotoxins of Staphylococcus aureus–learnings for designing novel therapeutics. Adv Exp Med Biol 966:15–35

    Article  PubMed  Google Scholar 

  11. Barash JR, Arnon SS (2013) A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins. J Infect Dis 209(2):183–191

    Article  PubMed  CAS  Google Scholar 

  12. Berends ET, Kuipers A, Ravesloot MM, Urbanus RT, Rooijakkers SH (2014) Bacteria under stress by complement and coagulation. FEMS Microbiol Rev 38(6):1146–1171

    Article  CAS  PubMed  Google Scholar 

  13. Brady LJ (2005) Antibody-mediated immunomodulation: a strategy to improve host responses against microbial antigens. Infect Immun 73(2):671–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Calmettes C, Ing C, Buckwalter CM, El Bakkouri M, Lai CC-L, Pogoutse A, Gray-Owen SD, Pomès R, Moraes TF (2015) The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD. Nat Commun 6:7996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cano V, March C, Insua JL, Aguiló N, Llobet E, Moranta D, Regueiro V, Brennan GP, Millán-Lou MI, Martín C (2015) Klebsiella pneumoniae survives within macrophages by avoiding delivery to lysosomes. Cell Microbiol 17(11):1537–1560

    Article  CAS  PubMed  Google Scholar 

  16. Carter GP, Chakravorty A, Nguyen TAP, Mileto S, Schreiber F, Li L, Howarth P, Clare S, Cunningham B, Sambol SP (2015) Defining the roles of TcdA and TcdB in localized gastrointestinal disease, systemic organ damage, and the host response during Clostridium difficile infections. MBio 6(3):e00551–e00515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Casadevall A, Dadachova E, Pirofski L-A (2004) Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2(9):695

    Article  CAS  PubMed  Google Scholar 

  18. Cassidy SK, O’Riordan MX (2013) More than a pore: the cellular response to cholesterol-dependent cytolysins. Toxins 5(4):618–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cerasi M, Ammendola S, Battistoni A (2013) Competition for zinc binding in the host-pathogen interaction. Front Cell Infect Microbiol 3

    Google Scholar 

  20. Chen Z, Moayeri M, Purcell R (2011) Monoclonal antibody therapies against anthrax. Toxins (Basel) 3:1004–1019

    Article  CAS  Google Scholar 

  21. Coates AR, Halls G, Hu Y (2011) Novel classes of antibiotics or more of the same? Br J Pharmacol 163(1):184–194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cross AS (2014) Anti-endotoxin vaccines: back to the future. Virulence 5(1):219–225

    Article  PubMed  Google Scholar 

  23. Czaplewski L, Bax R, Clokie M, Dawson M, Fairhead H, Fischetti VA, Foster S, Gilmore BF, Hancock RE, Harper D (2016) Alternatives to antibiotics – a pipeline portfolio review. Lancet Infect Dis 16(2):239–251

    Article  CAS  PubMed  Google Scholar 

  24. Dal Peraro M, Van Der Goot FG (2016) Pore-forming toxins: ancient, but never really out of fashion. Nat Rev Microbiol 14(2):77

    Article  PubMed  CAS  Google Scholar 

  25. Di Padova F, Brade H, Barclay GR, Poxton I, Liehl E, Schuetze E, Kocher H, Ramsay G, Schreier M, McClelland D (1993) A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides. Infect Immun 61(9):3863–3872

    PubMed  PubMed Central  Google Scholar 

  26. Diago-Navarro E, Calatayud-Baselga I, Sun D, Khairallah C, Mann I, Ulacia-Hernando A, Sheridan B, Shi M, Fries BC (2017) Antibody-based immunotherapy to treat and prevent infection with Hypervirulent Klebsiella pneumoniae. Clin Vaccine Immunol 24(1):e00456–e00416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dickey SW, Cheung GY, Otto M (2017) Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance. Nat Rev Drug Discov 16:457–471

    Article  CAS  PubMed  Google Scholar 

  28. Diep BA, Le VT, Visram ZC, Rouha H, Stulik L, Dip EC, Nagy G, Nagy E (2016) Improved protection in a rabbit model of community-associated methicillin-resistant Staphylococcus aureus necrotizing pneumonia upon neutralization of leukocidins in addition to alpha-hemolysin. Antimicrob Agents Chemother 60(10):6333–6340

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. DiGiandomenico A, Keller AE, Gao C, Rainey GJ, Warrener P, Camara MM, Bonnell J, Fleming R, Bezabeh B, Dimasi N (2014) A multifunctional bispecific antibody protects against Pseudomonas aeruginosa. Sci Transl Med 6(262):262ra155

    Article  PubMed  CAS  Google Scholar 

  30. DuMont AL, Torres VJ (2014) Cell targeting by the Staphylococcus aureus pore-forming toxins: it’s not just about lipids. Trends Microbiol 22(1):21–27

    Article  CAS  PubMed  Google Scholar 

  31. EMEA (2007) Refusal Chmp assessment report for Mycograb London

    Google Scholar 

  32. Espina M, Olive AJ, Kenjale R, Moore DS, Ausar SF, Kaminski RW, Oaks EV, Middaugh CR, Picking WD, Picking WL (2006) IpaD localizes to the tip of the type III secretion system needle of Shigella flexneri. Infect Immun 74(8):4391–4400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Falugi F, Kim HK, Missiakas DM, Schneewind O (2013) Role of protein A in the evasion of host adaptive immune responses by Staphylococcus aureus. MBio 4(5):e00575–e00513

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Fan G, Wang Z, Hao M, Li J (2015) Bispecific antibodies and their applications. J Hematol Oncol 8(1):130

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Foletti D, Strop P, Shaughnessy L, Hasa-Moreno A, Casas MG, Russell M, Bee C, Wu S, Pham A, Zeng Z (2013) Mechanism of action and in vivo efficacy of a human-derived antibody against Staphylococcus aureus α-hemolysin. J Mol Biol 425(10):1641–1654

    Article  CAS  PubMed  Google Scholar 

  36. Foletti DL, Riggers JFC, Glanville JEG, Shaughnessy LMB, Shelton DL, Strop P, Zhai W (2014) Staphylococcus aureus specific antibodies and uses thereof. Google Patents

    Google Scholar 

  37. Fraunholz M, Sinha B (2012) Intracellular Staphylococcus aureus: live-in and let die. Front Cell Infect Microbiol 2:43

    Article  PubMed  PubMed Central  Google Scholar 

  38. Garcia-Rodriguez C, Levy R, Arndt JW, Forsyth CM, Razai A, Lou J, Geren I, Stevens RC, Marks JD (2007) Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin. Nat Biotechnol 25(1):107

    Article  CAS  PubMed  Google Scholar 

  39. Garcia-Rodriguez C, Geren IN, Lou J, Conrad F, Forsyth C, Wen W, Chakraborti S, Zao H, Manzanarez G, Smith TJ, Brown J, Tepp WH, Liu N, Wijesuriya S, Tomic MT, Johnson EA, Smith LA, Marks JD (2011) Neutralizing human monoclonal antibodies binding multiple serotypes of botulinum neurotoxin. Protein Eng Des Sel 24(3):321–331

    Article  CAS  PubMed  Google Scholar 

  40. García-Suárez MDM, Cima-Cabal MD, Flórez N, García P, Cernuda-Cernuda R, Astudillo A, Vázquez F, De Los Toyos JR, Méndez FJ (2004) Protection against pneumococcal pneumonia in mice by monoclonal antibodies to pneumolysin. Infect Immun 72(8):4534–4540

    Article  PubMed Central  CAS  Google Scholar 

  41. Getahun A, Heyman B (2006) How antibodies act as natural adjuvants. Immunol Lett 104(1):38–45

    Article  CAS  PubMed  Google Scholar 

  42. Goel VK, Kapil A (2001) Monoclonal antibodies against the iron regulated outer membrane proteins of Acinetobacter baumannii are bactericidal. BMC Microbiol 1(1):16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gomery K, Müller-Loennies S, Brooks CL, Brade L, Kosma P, Di Padova F, Brade H, Evans SV (2012) Antibody WN1 222-5 mimics toll-like receptor 4 binding in the recognition of LPS. Proc Natl Acad Sci 109(51):20877–20882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gordon D, Rice J (1988) Opsonin-dependent and independent surface phagocytosis of S. aureus proceeds independently of complement and complement receptors. Immunology 64(4):709

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Goulart C, Darrieux M, Rodriguez D, Pimenta FC, Brandileone MCC, de Andrade ALS, Leite LC (2011) Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells. Vaccine 29(8):1634–1642

    Article  CAS  PubMed  Google Scholar 

  46. Goure J, Broz P, Attree O, Cornelis GR, Attree I (2005) Protective anti-V antibodies inhibit Pseudomonas and Yersinia translocon assembly within host membranes. J Infect Dis 192(2):218–225

    Article  CAS  PubMed  Google Scholar 

  47. Greig SL (2016) Obiltoxaximab: first global approval. Drugs 76(7):823–830

    Article  CAS  PubMed  Google Scholar 

  48. Gribenko AV, Parris K, Mosyak L, Li S, Handke L, Hawkins JC, Severina E, Matsuka YV, Anderson AS (2016) High resolution mapping of bactericidal monoclonal antibody binding epitopes on Staphylococcus aureus antigen MntC. PLoS Pathog 12(9):e1005908

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Gunn JS, Ernst RK (2007) The structure and function of Francisella lipopolysaccharide. Ann N Y Acad Sci 1105(1):202–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hammers C, Songa EB, Bendahman N, Hammers R (1993) Naturally occurring antibodies devoid of light chains. Nature 363(6428):446–448

    Article  CAS  PubMed  Google Scholar 

  51. Hammer ND, Skaar EP (2011) Molecular mechanisms of Staphylococcus aureus iron acquisition. Annu Rev Microbiol 65:129–147

    Article  CAS  PubMed  Google Scholar 

  52. Hilliard JJ, Datta V, Tkaczyk C, Hamilton M, Sadowska A, Jones-Nelson O, O’Day T, Weiss WJ, Szarka S, Nguyen V (2015) Anti-alpha-toxin monoclonal antibody and antibiotic combination therapy improves disease outcome and accelerates healing in a Staphylococcus aureus dermonecrosis model. Antimicrob Agents Chemother 59(1):299–309

    Article  PubMed  CAS  Google Scholar 

  53. Horn MP, Zuercher AW, Imboden MA, Rudolf MP, Lazar H, Wu H, Hoiby N, Fas SC, Lang AB (2010) Preclinical in vitro and in vivo characterization of the fully human monoclonal IgM antibody KBPA101 specific for Pseudomonas aeruginosa serotype IATS-O11. Antimicrob Agents Chemother 54(6):2338–2344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hua L, Hilliard J, Shi Y, Tkaczyk C, Cheng L, Yu X, Datta V, Ren S, Feng H, Zinsou R (2014) Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia. Antimicrob Agents Chemother 58(2):1108–1117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hua L, Cohen T, Shi Y, Datta V, Hilliard J, Tkaczyk C, Suzich J, Stover C, Sellman B (2015) MEDI4893* promotes survival and extends the antibiotic treatment window in a Staphylococcus aureus immunocompromised pneumonia model. Antimicrob Agents Chemother 59(8):4526–4532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hubert K, Devos N, Mordhorst I, Tans C, Baudoux G, Feron C, Goraj K, Tommassen J, Vogel U, Poolman JT (2013) ZnuD, a potential candidate for a simple and universal Neisseria meningitidis vaccine. Infect Immun 81(6):1915–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Isoda R, Robinette RA, Pinder TL, McArthur WP, Brady LJ (2007) Basis of beneficial immunomodulation by monoclonal antibodies against Streptococcus mutans adhesin P1. FEMS Immunol Med Microbiol 51(1):102–111

    Article  CAS  PubMed  Google Scholar 

  58. Ivanov MI, Hill J, Bliska JB (2014) Direct neutralization of type III effector translocation by the variable region of a monoclonal antibody to Yersinia pestis LcrV. Clin Vaccine Immunol 21(5):667–673

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Jacobs T, Cima-Cabal MD, Darji A, Méndez F, Vázquez F, Jacobs A, Shimada Y, Ohno-Iwashita Y, Weiss S, de los Toyos JR (1999) The conserved undecapeptide shared by thiol-activated cytolysins is involved in membrane binding. FEBS Lett 459(3):463–466

    Article  CAS  PubMed  Google Scholar 

  60. Jones CH, Pinkner JS, Roth R, Heuser J, Nicholes AV, Abraham SN, Hultgren SJ (1995) FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae. Proc Natl Acad Sci 92(6):2081–2085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kaper JB, Nataro JP, Mobley HL (2004) Pathogenic Escherichia coli. Nat Rev Microbiol 2(2):123

    Article  CAS  PubMed  Google Scholar 

  62. Karauzum H, Adhikari RP, Sarwar J, Devi VS, Abaandou L, Haudenschild C, Mahmoudieh M, Boroun AR, Vu H, Nguyen T (2013) Structurally designed attenuated subunit vaccines for S. aureus LukS-PV and LukF-PV confer protection in a mouse bacteremia model. PLoS One 8(6):e65384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kehl-Fie TE, Skaar EP (2010) Nutritional immunity beyond iron: a role for manganese and zinc. Curr Opin Chem Biol 14(2):218–224

    Article  CAS  PubMed  Google Scholar 

  64. Kelly-Quintos C, Cavacini LA, Posner MR, Goldmann D, Pier GB (2006) Characterization of the opsonic and protective activity against Staphylococcus aureus of fully human monoclonal antibodies specific for the bacterial surface polysaccharide poly-N-acetylglucosamine. Infect Immun 74(5):2742–2750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kim P-H, Iaconis JP, Rolfe RD (1987) Immunization of adult hamsters against Clostridium difficile-associated ileocecitis and transfer of protection to infant hamsters. Infect Immun 55(12):2984–2992

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Kim KS, Kang JH, Cross AS, Kaufman B, Zollinger W, Sadoff J (1988) Functional activities of monoclonal antibodies to the O side chain of Escherichia coli lipopolysaccharides in vitro and in vivo. J Infect Dis 157(1):47–53

    Article  CAS  PubMed  Google Scholar 

  67. Kim HK, Emolo C, DeDent AC, Falugi F, Missiakas DM, Schneewind O (2012) Protein A-specific monoclonal antibodies and prevention of Staphylococcus aureus disease in mice. Infect Immun 80(10):3460–3470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kimmitt PT, Harwood CR, Barer MR (2000) Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response. Emerg Infect Dis 6(5):458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kisiela DI, Avagyan H, Friend D, Jalan A, Gupta S, Interlandi G, Liu Y, Tchesnokova V, Rodriguez VB, Sumida JP (2015) Inhibition and reversal of microbial attachment by an antibody with parasteric activity against the FimH adhesin of uropathogenic E. coli. PLoS Pathog 11(5):e1004857

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Kong C, Neoh H-m, Nathan S (2016) Targeting Staphylococcus aureus toxins: a potential form of anti-virulence therapy. Toxins 8(3):72

    Article  PubMed Central  CAS  Google Scholar 

  71. Kontermann RE, Brinkmann U (2015) Bispecific antibodies. Drug Discov Today 20(7):838–847

    Article  CAS  PubMed  Google Scholar 

  72. La Ragione RM, Patel S, Maddison B, Woodward MJ, Best A, Whitelam GC, Gough KC (2006) Recombinant anti-EspA antibodies block Escherichia coli O157: H7-induced attaching and effacing lesions in vitro. Microbes Infect 8(2):426–433

    Article  PubMed  CAS  Google Scholar 

  73. Laarman A, Milder F, van Strijp J, Rooijakkers S (2010) Complement inhibition by gram-positive pathogens: molecular mechanisms and therapeutic implications. J Mol Med 88(2):115–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lacy DB, Stevens RC (1999) Sequence homology and structural analysis of the Clostridial neurotoxins. J Mol Biol 291(5):1091–1104

    Article  CAS  PubMed  Google Scholar 

  75. LaRocca TJ, Katona LI, Thanassi DG, Benach JL (2008) Bactericidal action of a complement-independent antibody against relapsing fever Borrelia resides in its variable region. J Immunol 180(9):6222–6228

    Article  CAS  PubMed  Google Scholar 

  76. LaRocca TJ, Holthausen DJ, Hsieh C, Renken C, Mannella CA, Benach JL (2009) The bactericidal effect of a complement-independent antibody is osmolytic and specific to Borrelia. Proc Natl Acad Sci 106(26):10752–10757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, DePalatis L, Raab H, Hazenbos WL, Morisaki JH (2015) Novel antibody–antibiotic conjugate eliminates intracellular S. aureus. Nature 527(7578):323–328

    Article  CAS  PubMed  Google Scholar 

  78. Li X, Wang X, Thompson CD, Park S, Park WB, Lee JC (2016) Preclinical efficacy of clumping factor A in prevention of Staphylococcus aureus infection. MBio 7(1):e02232–e02215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Libby JM, Jortner BS, Wilkins TD (1982) Effects of the two toxins of Clostridium difficile in antibiotic-associated cecitis in hamsters. Infect Immun 36(2):822–829

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Lo K-M, Leger O, Hock B (2014) Antibody engineering. Microbiol Spectr 2(1)

    Google Scholar 

  81. Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, Nichol G, Thomas WD Jr, Leney M, Sloan S (2010) Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 362(3):197

    Article  CAS  PubMed  Google Scholar 

  82. Lydon NB (2016) Immunoglobulins and variants directed against pathogenic microbes. Google Patents

    Google Scholar 

  83. MacLennan CA, Gilchrist JJ, Gordon MA, Cunningham AF, Cobbold M, Goodall M, Kingsley RA, van Oosterhout JJ, Msefula CL, Mandala WL (2010) Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults. Science 328(5977):508–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Maira-Litrán T, Kropec A, Goldmann DA, Pier GB (2005) Comparative opsonic and protective activities of Staphylococcus aureus conjugate vaccines containing native or deacetylated staphylococcal poly-N-acetyl-β-(1-6)-glucosamine. Infect Immun 73(10):6752–6762

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Martin WL, West AP, Gan L, Bjorkman PJ (2001) Crystal structure at 2.8 Å of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 7(4):867–877

    Article  CAS  PubMed  Google Scholar 

  86. Mathers AJ, Peirano G, Pitout JD (2015) The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev 28(3):565–591

    Article  PubMed  PubMed Central  Google Scholar 

  87. Melton-Celsa AR, O’Brien AD (2015) New therapeutic developments against Shiga toxin-producing Escherichia coli. Enterohemorrhagic Escherichia coli and other Shiga toxin-producing E. coli. Am Soc Microbiol 361–380

    Google Scholar 

  88. Migone T-S, Subramanian GM, Zhong J, Healey LM, Corey A, Devalaraja M, Lo L, Ullrich S, Zimmerman J, Chen A (2009) Raxibacumab for the treatment of inhalational anthrax. N Engl J Med 361(2):135–144

    Article  CAS  PubMed  Google Scholar 

  89. Milla CE, Chmiel JF, Accurso FJ, VanDevanter DR, Konstan MW, Yarranton G, Geller DE (2014) Anti-PcrV antibody in cystic fibrosis: a novel approach targeting Pseudomonas aeruginosa airway infection. Pediatr Pulmonol 49(7):650–658

    Article  PubMed  Google Scholar 

  90. Modi SR, Collins JJ, Relman DA (2014) Antibiotics and the gut microbiota. J Clin Invest 124(10):4212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Mosley JF, II LLS, Parke CK, Brown JA, Wilson AL, Gibbs LV (2016) Ceftazidime-avibactam (Avycaz): for the treatment of complicated intra-abdominal and urinary tract infections. Pharm Ther 41(8):479

    Google Scholar 

  92. Müller-Loennies S, Brade L, MacKenzie CR, Di Padova FE, Brade H (2003a) Identification of a cross-reactive epitope widely present in lipopolysaccharide from enterobacteria and recognized by the cross-protective monoclonal antibody WN1 222-5. J Biol Chem 278(28):25618–25627

    Article  PubMed  CAS  Google Scholar 

  93. Müller-Loennies S, Lindner B, Brade H (2003b) Structural analysis of oligosaccharides from lipopolysaccharide (LPS) of Escherichia coli K12 strain W3100 reveals a link between inner and outer core LPS biosynthesis. J Biol Chem 278(36):34090–34101

    Article  PubMed  CAS  Google Scholar 

  94. Nagy E, Badarau A, Rouha H, Stulik L, Mirkina I, Battles MB, Nielson N (2016) Antibody directed against immunoglobulin-binding proteins of s. aureus. Google Patents

    Google Scholar 

  95. Nayak S, Griffiss J, McKenzie R, Fuchs E, Jurao R, An A, Ahene A, Tomic M, Hendrix C, Zenilman J (2014) Safety and pharmacokinetics of XOMA 3AB, a novel mixture of three monoclonal antibodies against botulinum toxin A. Antimicrob Agents Chemother 58(9):5047–5053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Nazareth H, Genagon SA, Russo TA (2007) Extraintestinal pathogenic Escherichia coli survives within neutrophils. Infect Immun 75(6):2776–2785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Nguyen AW, Wagner EK, Laber JR, Goodfield LL, Smallridge WE, Harvill ET, Papin JF, Wolf RF, Padlan EA, Bristol A (2015) A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. Sci Transl Med 7(316):316ra195

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. 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):11346–11350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Nowling JM, Philipp MT (1999) Killing of Borrelia burgdorferi by antibody elicited by OspA vaccine is inefficient in the absence of complement. Infect Immun 67(1):443–445

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Obrig TG (2010) Escherichia coli Shiga toxin mechanisms of action in renal disease. Toxins 2(12):2769–2794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Ofosu A (2016) Clostridium difficile infection: a review of current and emerging therapies. Ann Gastroenterol 29(2):147

    Article  PubMed  PubMed Central  Google Scholar 

  102. Oganesyan V, Peng L, Damschroder MM, Cheng L, Sadowska A, Tkaczyk C, Sellman BR, Wu H, Dall’Acqua WF (2014) Mechanisms of neutralization of a human anti-α-toxin antibody. J Biol Chem 289(43):29874–29880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Pancari G, Fan H, Smith S, Joshi A, Haimbach R, Clark D, Li Y, Hua J, McKelvey T, Ou Y (2012) Characterization of the mechanism of protection mediated by CS-D7, a monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB). Front Cell Infect Microbiol 2:36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Park BS, Song DH, Kim HM, Choi B-S, Lee H, Lee J-O (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458(7242):1191–1195

    Article  CAS  PubMed  Google Scholar 

  105. Park IH, Lin J, Choi JE, Shin J-S (2014) Characterization of Escherichia coli K1 colominic acid-specific murine antibodies that are cross-protective against Neisseria meningitidis groups B, C, and Y. Mol Immunol 59(2):142–153

    Article  CAS  PubMed  Google Scholar 

  106. Pier GB, Boyer D, Preston M, Coleman FT, Llosa N, Mueschenborn-Koglin S, Theilacker C, Goldenberg H, Uchin J, Priebe GP (2004) Human monoclonal antibodies to Pseudomonas aeruginosa alginate that protect against infection by both mucoid and nonmucoid strains. J Immunol 173(9):5671–5678

    Article  CAS  PubMed  Google Scholar 

  107. Pinkston KL, Singh KV, Gao P, Wilganowski N, Robinson H, Ghosh S, Azhdarinia A, Sevick-Muraca EM, Murray BE, Harvey BR (2014) Targeting pili in enterococcal pathogenesis. Infect Immun 82(4):1540–1547

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Pohl MA, Rivera J, Nakouzi A, Chow S-K, Casadevall A (2013) Combinations of monoclonal antibodies to anthrax toxin manifest new properties in neutralization assays. Infect Immun 81(6):1880–1888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Que Y-A, Lazar H, Wolff M, François B, Laterre P-F, Mercier E, Garbino J, Pagani J-L, Revelly J-P, Mus E (2014) Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia. Eur J Clin Microbiol Infect Dis 33(10):1861–1867

    Article  CAS  PubMed  Google Scholar 

  110. Raff HV, Devereux D, Shuford W, Abbott-Brown D, Maloney G (1988) Human monoclonal antibody with protective activity for Escherichia coli K1 and Neisseria meningitidis group B infections. J Infect Dis 157(1):118–126

    Article  CAS  PubMed  Google Scholar 

  111. Rasmussen SK, Næsted H, Müller C, Tolstrup AB, Frandsen TP (2012) Recombinant antibody mixtures: production strategies and cost considerations. Arch Biochem Biophys 526(2):139–145

    Article  CAS  PubMed  Google Scholar 

  112. Ritts R (1990) Antibiotics as biological response modifiers. J Antimicrob Chemother 26(suppl_C):31–36

    Article  CAS  PubMed  Google Scholar 

  113. Robbie GJ, Criste R, Dall’Acqua WF, Jensen K, Patel NK, Losonsky GA, Griffin MP (2013) A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother 57(12):6147–6153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Rouha H, Badarau A, Visram ZC, Battles MB, Prinz B, Magyarics Z, Nagy G, Mirkina I, Stulik L, Zerbs M (2015) Five birds, one stone: neutralization of α-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single human monoclonal antibody. MAbs, Taylor & Francis

    Google Scholar 

  115. Rudolf M, Koch H (2011) Human monoclonal antibody against s. aureus derived alpha-toxin and its use in treating or preventing abscess formation. Google Patents

    Google Scholar 

  116. Rukavina T, Ticac B, Susa M, Jendrike N, Jonjíc S, Lucin P, Marre R, Doric M, Trautmann M (1997) Protective effect of antilipopolysaccharide monoclonal antibody in experimental Klebsiella infection. Infect Immun 65(5):1754–1760

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Salha D, Szeto J, Myers L, Claus C, Sheung A, Tang M, Ljutic B, Hanwell D, Ogilvie K, Ming M (2012) Neutralizing antibodies elicited by a novel detoxified pneumolysin derivative, PlyD1, provide protection against both pneumococcal infection and lung injury. Infect Immun 80(6):2212–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Sansonetti P (2001) Phagocytosis of bacterial pathogens: implications in the host response. Semin Immunol 13:381–390. Elsevier

    Article  CAS  PubMed  Google Scholar 

  119. Schelonka RL, Infante AJ (1998) Neonatal immunology. Semin Perinatol 22:2–14. Elsevier

    Article  CAS  PubMed  Google Scholar 

  120. Schuurman J, Parren PWHI (2016) Editorial overview: special section: new concepts in antibody therapeutics: what’s in store for antibody therapy? Curr Opin Immunol 40:vii–xiii

    Article  CAS  PubMed  Google Scholar 

  121. Sellman B, Tkaczyk C, Hua L, Chowdhury P, Varkey R, Damschroder M, Peng L, Oganesyan V, Hilliard JJ (2012) Antibodies that specifically bind staphylococcus aureus alpha toxin and methods of use. Google Patents

    Google Scholar 

  122. Simard J (2015) Compositions and methods for treating and preventing staphylococcus aureus infections. Google Patents

    Google Scholar 

  123. Smiley ST (2008) Immune defense against pneumonic plague. Immunol Rev 225(1):256–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Steeland S, Vandenbroucke RE, Libert C (2016) Nanobodies as therapeutics: big opportunities for small antibodies. Drug Discov Today 21(7):1076–1113

    Article  CAS  PubMed  Google Scholar 

  125. Steele J, Mukherjee J, Parry N, Tzipori S (2013) Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease. J Infect Dis 207(2):323–330

    Article  CAS  PubMed  Google Scholar 

  126. Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE (2007) Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis 195(2):202–211

    Article  CAS  PubMed  Google Scholar 

  127. Stork M, Bos MP, Jongerius I, de Kok N, Schilders I, Weynants VE, Poolman JT, Tommassen J (2010) An outer membrane receptor of Neisseria meningitidis involved in zinc acquisition with vaccine potential. PLoS Pathog 6(7):e1000969

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Szijártó V, Guachalla LM, Visram ZC, Hartl K, Varga C, Mirkina I, Zmajkovic J, Badarau A, Zauner G, Pleban C (2015) Bactericidal monoclonal antibodies specific to the lipopolysaccharide O antigen from multidrug-resistant Escherichia coli clone ST131-O25b: H4 elicit protection in mice. Antimicrob Agents Chemother 59(6):3109–3116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Szijártó V, Guachalla LM, Hartl K, Varga C, Banerjee P, Stojkovic K, Kaszowska M, Nagy E, Lukasiewicz J, Nagy G (2016) Both clades of the epidemic KPC-producing Klebsiella pneumoniae clone ST258 share a modified galactan O-antigen type. Int J Med Microbiol 306(2):89–98

    Article  PubMed  CAS  Google Scholar 

  130. Szijártó V, Guachalla LM, Hartl K, Varga C, Badarau A, Mirkina I, Visram ZC, Stulik L, Power CA, Nagy E (2017) Endotoxin neutralization by an O-antigen specific monoclonal antibody: a potential novel therapeutic approach against Klebsiella pneumoniae ST258. Virulence 8:1203–1215

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Thammavongsa V, Rauch S, Kim HK, Missiakas DM, Schneewind O (2015) Protein A-neutralizing monoclonal antibody protects neonatal mice against Staphylococcus aureus. Vaccine 33(4):523–526

    Article  CAS  PubMed  Google Scholar 

  132. Tkaczyk C, Hamilton M, Sadowska A, Shi Y, Chang C, Chowdhury P, Buonapane R, Xiao X, Warrener P, Mediavilla J (2016) Targeting alpha toxin and ClfA with a multimechanistic monoclonal-antibody-based approach for prophylaxis of serious Staphylococcus aureus disease. MBio 7(3):e00528–e00516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Torres VJ, Brezski RJ, Lynch A, Strohl W, Whitaker B, Chiu M, Buckley PT, Dorn K, Kinder M (2017) Compositions and methods for phagocyte delivery of anti-staphylococcal agents. Google Patents

    Google Scholar 

  134. Underhill DM, Ozinsky A (2002) Phagocytosis of microbes: complexity in action. Annu Rev Immunol 20(1):825–852

    Article  CAS  PubMed  Google Scholar 

  135. Voth DE, Ballard JD (2005) Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 18(2):247–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Vrieling M, Boerhout EM, van Wigcheren GF, Koymans KJ, Mols-Vorstermans TG, de Haas CJC, Aerts PC, Daemen IJJM, van Kessel KPM, Koets AP, Rutten VPMG, Nuijten PJM, van Strijp JAG, Benedictus L (2016) LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis. Sci Rep 6:37759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Vu DM, Pajon R, Reason DC, Granoff DM (2012) A broadly cross-reactive monoclonal antibody against an epitope on the N-terminus of meningococcal fHbp. Sci Rep 2:341

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Vuong C, Yeh AJ, Cheung GY, Otto M (2016) Investigational drugs to treat methicillin-resistant Staphylococcus aureus. Expert Opin Investig Drugs 25(1):73–93

    Article  CAS  PubMed  Google Scholar 

  139. Wang Q, Chang C-s, Pennini M, Pelletier M, Rajan S, Zha J, Chen Y, Cvitkovic R, Sadowska A, Heidbrink Thompson J (2016) Target-agnostic identification of functional monoclonal antibodies against Klebsiella pneumoniae multimeric MrkA fimbrial subunit. J Infect Dis 213(11):1800–1808

    Article  CAS  PubMed  Google Scholar 

  140. Warrener P, Varkey R, Bonnell JC, DiGiandomenico A, Camara M, Cook K, Peng L, Zha J, Chowdury P, Sellman B (2014) A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models. Antimicrob Agents Chemother 58(8):4384–4391

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. West AP, Bjorkman PJ (2000) Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor. Biochemistry 39(32):9698–9708

    Article  CAS  PubMed  Google Scholar 

  142. Whaley K, Schwaeble W (1997) Complement and complement deficiencies. Seminars in liver disease, © 1997 by Thieme Medical Publishers, Inc

    Google Scholar 

  143. Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T, Cornely OA, Rahav G, Bouza E, Lee C (2017) Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med 376(4):305–317

    Article  CAS  PubMed  Google Scholar 

  144. Woodford N, Turton JF, Livermore DM (2011) Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol Rev 35(5):736–755

    Article  CAS  PubMed  Google Scholar 

  145. Wu H-J, Wang AH, Jennings MP (2008) Discovery of virulence factors of pathogenic bacteria. Curr Opin Chem Biol 12(1):93–101

    Article  CAS  PubMed  Google Scholar 

  146. XBiotech I (2017) XBiotech announces top-line results for 514G3 antibody therapy in serious Staphylococcus aureus infections. Retrieved April, 03, 2017, from https://globenewswire.com/news-release/2017/04/03/953500/0/en/XBiotech-Announces-Top-Line-Results-for-514G3-Antibody-Therapy-in-Serious-Staphylococcus-aureus-Infections.html

  147. Xenopoulos A (2015) A new, integrated, continuous purification process template for monoclonal antibodies: process modeling and cost of goods studies. J Biotechnol 213:42–53

    Article  CAS  PubMed  Google Scholar 

  148. Yamada T (2011) Therapeutic monoclonal antibodies. Keio J Med 60(2):37–46

    Article  CAS  PubMed  Google Scholar 

  149. Yang Z, Ramsey J, Hamza T, Zhang Y, Li S, Yfantis HG, Lee D, Hernandez LD, Seghezzi W, Furneisen JM (2015) Mechanisms of protection against Clostridium difficile infection by the monoclonal antitoxin antibodies actoxumab and bezlotoxumab. Infect Immun 83(2):822–831

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Yu X-Q, Robbie GJ, Wu Y, Esser MT, Jensen K, Schwartz HI, Bellamy T, Hernandez-Illas M, Jafri HS (2017) Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-Staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrob Agents Chemother 61(1):e01020–e01016

    Article  CAS  PubMed  Google Scholar 

  151. Zaidi T, Pier GB (2008) Prophylactic and therapeutic efficacy of a fully human immunoglobulin G1 monoclonal antibody to Pseudomonas aeruginosa alginate in murine keratitis infection. Infect Immun 76(10):4720–4725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, Lazar GA, Roopenian DC, Desjarlais JR (2010) Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Arsanis Biosciences GmbH/Arsanis, Inc, Vienna, Austria

    Eszter Nagy, Gábor Nagy, Christine A. Power, Adriana Badarau & Valéria Szijártó

Authors
  1. Eszter Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gábor Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine A. Power
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adriana Badarau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Valéria Szijártó
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eszter Nagy .

Editor information

Editors and Affiliations

  1. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia

    Theam Soon Lim

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nagy, E., Nagy, G., Power, C.A., Badarau, A., Szijártó, V. (2017). Anti-bacterial Monoclonal Antibodies. In: Lim, T. (eds) Recombinant Antibodies for Infectious Diseases. Advances in Experimental Medicine and Biology, vol 1053. Springer, Cham. https://doi.org/10.1007/978-3-319-72077-7_7

Download citation

Publish with us

Policies and ethics

Search

Navigation