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Volume 2, Number 3—July 1996

Antibody-Based Therapies for Emerging Infectious Diseases

Arturo CasadevallComments to Author 
Author affiliation: Albert Einstein College of Medicine, Bronx, New York, USA

Main Article

Table 1

Serum therapy, human MAbs, and antimicrobial chemotherapy

Antibody therapy
Chemotherapy Comment
Immune serum Human MAb
Specificity Narrow Narrow Broad Narrow specificity avoids selection of resistant organims among nontargeted microbes.
Narrow specificity requires a precise diagnosis before use.
Source Animals
Humans Tissue culture
Fermentation Fermentation
synthesis Before antibiotics, most serum preparations were from horses and rabbits. MAbs are produced by tissue culture techniques.
Industrial production of MAbs may utilize immunoglobulin synthesis in yeast, bacteria, or plants.
Toxicity High Low Low Toxicity of serum was due to allergic reactions to animals protein. Human immunoglobulin preparations are well tolerated (42). Antiidiotypic responses remain a problem for humanized MAb therapy.
Cost High High Low Serum therapy for pneumococcal pneumonia in the 1930s was costly (6). Immunoglobulin therapy remains very expensive.
Administration Difficult Easy Easy Serum therapy required considerable expertise, and because of life-threatening allergic reactions, dosage was often based on clinical experience.
Pharmacokinetics Variable Consistent Consistent Pharmacokinetics of hererologous polyclonal antibody depends on multiple variables, e.g., animal source, isotype composition, and immune status of the recipient.
Human MAbs are homogeneous reagents and can be expected to have more consistent pharmacokinetics.
of action Antimicrobia
Toxin neutralization Antimicrobial
Toxin neutralization Antimicrobial Conventional antimicrobial chemotherapy kills or inhibits the replication of microorganisms. Antibodies function through a variety of mechanisms, e.g., promoting complement-mediated lysis, enhancing antimicrobial efficacy of host effector cells, promoting phagocytosis, preventing attachment, and neutralizing toxins.

Main Article

  1. Service  RF. Antibiotics that resist resistance. Science. 1995;270:7247. DOIPubMedGoogle Scholar
  2. Berkelman  RL, Bryan  RT, Osterholm  MT, LeDuc  JW, Hughes  JM. Infectious disease surveillance: a crumbling foundation. Science. 1994;264:36870. DOIPubMedGoogle Scholar
  3. Joshi  N, Milfred  D. The use and misuse of new antibiotics. Arch Intern Med. 1995;155:56977. DOIPubMedGoogle Scholar
  4. Mumford  RS, Murphy  TV. Antimicrobial resistance in Streptococcus pneumoniae: can immunization prevent its spread. J Investig Med. 1994;42:61321.PubMedGoogle Scholar
  5. Roilides  E, Pizzo  PA. Modulation of host defenses by cytokines: evolving adjuncts in prevention and treatment of serious infections in immunocompromised hosts. Clin Infect Dis. 1992;15:50824.PubMedGoogle Scholar
  6. Casadevall  A, Scharff  MD. “Serum therapy” revisited: animal models of infection and the development of passive antibody therapy. Antimicrob Agents Chemother. 1994;38:1695702.PubMedGoogle Scholar
  7. Casadevall  A, Scharff  MD. Return to the past: the case for antibody-based therapies in infectious diseases. Clin Infect Dis. 1995;21:15061.PubMedGoogle Scholar
  8. Rackemann  FM. Allergy: serum reactions, with particular reference to the prevention and treatment of tetanus. JAMA. 1942;226:72633.
  9. Feinberg  SM. The therapy of (horse) serum reactions. general rules in the administration of therapeutic serums. JAMA. 1936;107:17179.
  10. Finland  M. The use of serum, sulfanilamide, and sulfapyridine in the treatment of pneumococcic infections. Med Clin North Am. 1939;:12059.
  11. Colebrook  L, Maxted  WR. Streptococcal infections in mice treated by chemotherapy and serum. Lancet. 1940;1:218. DOIGoogle Scholar
  12. MacLeod  CM. Chemotherapy of pneumococcic pneumonia. JAMA. 1939;113:140510.
  13. Branham  SE. Sulphanilamide, serum, and combined drug and serum therapy in experimental meningococcus and pneumococcus infections in mice. Public Health Rep. 1938;52:68595.
  14. Sako  W, Dwan  PF, Platou  ES. Sulfanilamide and serum in the treatment and prophylaxis of scarlet fever. JAMA. 1938;111:9957.
  15. Alexander  HE. Treatment of Haemophilus influenzae infections and of meningococcic and pneumococcic meningitis. Am J Dis Child. 1943;66:17287.
  16. Waghelstein  JM. Sulfanilamide in the treatment of 106 patients with meningococcic infections. JAMA. 1938;111:21724.
  17. Dowling  HF, Abernethy  TJ. The treatment of pneumococcus pneumonia: a comparison of the results obtained with specific serum and sulfapyridine. Am J Med Sci. 1940;199:5562. DOIGoogle Scholar
  18. Cory  CW, Abbot  CE, Truszkowski  EG. Treatment of meninogococcic meningitis and septicemia. J Pediatr. 1944;25:3548. DOIGoogle Scholar
  19. Kohler  G, Milstein  C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:4957. DOIPubMedGoogle Scholar
  20. Wright  A, Shin  S-U, Morrison  SL. Genetically engineered antibodies: progress and prospects. Crit Rev Immunol. 1992;12:12568.PubMedGoogle Scholar
  21. Felton  LD. The units of protective antibody in antipneumococcus serum and antibody solution. J Infect Dis. 1928;43:53142.
  22. Weisman  LE, Cruess  DF, Fischer  GW. Opsonic activity of commercially available standard intravenous immunoglobulin preparations. Pediatr Infect Dis J. 1994;13:11225.PubMedGoogle Scholar
  23. Slade  HB. Human immunoglobulins for intravenous use and hepatitis C viral transmission. Clin Diagn Lab Immunol. 1994;1:6139.PubMedGoogle Scholar
  24. Lang  AB, Cryz  SJ, Schurch  U, Ganss  MT, Bruderer  U. Immunotherapy with human monoclonal antibodies. . J Immunol. 1993;151:46672.PubMedGoogle Scholar
  25. French  DL, Laskov  R, Scharff  MD. The role of somatic hypermutation in the generation of antibody diversity. Science. 1989;244:11527. DOIPubMedGoogle Scholar
  26. Casadevall  A. Antibody immunity and invasive fungal infections. Infect Immun. 1995;63:42118.PubMedGoogle Scholar
  27. Mukherjee  J, Zuckier  L, Scharff  MD, Casadevall  A. Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B. Antimicrob Agents Chemother. 1994;38:5807.PubMedGoogle Scholar
  28. Dromer  F, Charreire  J. Improved amphotericin B activity by a monoclonal anti-Cryptococcus neoformans antibody: study during murine cryptococcosis and mechanisms of action. J Infect Dis. 1991;163:111420.PubMedGoogle Scholar
  29. Mukherjee  J, Feldmesser  M, Scharff  MD, Casadevall  A. Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole activity. Antimicrob Agents Chemother. 1995;39:1398405.PubMedGoogle Scholar
  30. Feldmesser  M, Mukherjee  J, Casadevall  A. Combination of 5-flucytosine and capsule binding monoclonal antibody in therapy of murine Cryptococcus neoformans infections and in vitro. J Antimicrob Chemother. 1996. In press.PubMedGoogle Scholar
  31. Mazanec  MB, Kaetzel  CS, Lamm  ME, Fletcher  D, Nedrud  JG. Intracellular neutralization of virus by immunoglobulin A antibodies. Proc Natl Acad Sci U S A. 1992;89:69015. DOIPubMedGoogle Scholar
  32. Mineo  JR, Khan  IA, Kasper  LH. Toxoplasma gondii: A monoclonal antibody that inhibits intracellular replication. Exp Parasitol. 1994;79:35161. DOIPubMedGoogle Scholar
  33. Yanase  K, Smith  RM, Cizman  B, Foster  MH, Peahy  LD, Jarret  L, . A subgroup of murine monoclonal antideoxyribonucleic acid antibodies traverse the cytoplasm and enter the nucleous in a time and temperature-dependent manner. Lab Invest. 1994;71:5260.PubMedGoogle Scholar
  34. Heinzel  FP. Antibodies. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. New York: Churchill Livingstone, 1995:36-57.
  35. J Delaet  I, Boeye  A. Monoclonal antibodies that disrupt poliovirus only at fever temperatures. Virol. 1993;67:5299302.
  36. Smith  TW, Butler  VP, Haber  E, Fozzard  H, Marcus  FI, Bremmer  WF, Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. N Engl J Med. 1982;307:135762.PubMedGoogle Scholar
  37. Bobmer  M, Fournel  MA, Hinshaw  LB. Preclinical review of anti-tumor necrosis factor monoclonal antibodies. Crit Care Med. 1993;21:S4416.PubMedGoogle Scholar
  38. Zuckier  LS, Rodigues  LD, Scharff  MD. Immunologic and pharmacologic concepts of monoclonal antibodies. Semin Nucl Med. 1989;19:16686. DOIPubMedGoogle Scholar
  39. Waldman  TA, Strober  W. Metabolism of immunoglobulins. Prog Allergy. 1969;14:1110.
  40. Reilly  RM, Sandhu  J, Alvarez-Diez  TM, Gallinger  S, Kirsh  J, Stern  H. Problems of delivery of monoclonal antibodies: pharmaceutical and pharmacokinetic solutions. Clin Pharmacokinet. 1995;28:12642. DOIPubMedGoogle Scholar
  41. LoBuglio  AF, Wheeler  RH, Trang  J, Haynes  A, Rogers  K, Harvey  EB, . Mouse/human chimeric monoclonal antibody in man:kinetics and immune response. Proc Natl Acad Sci U S A. 1989;86:42204. DOIPubMedGoogle Scholar
  42. Pennington  JE. Newer uses of intravenous immunoglobulins as anti-infective agents. Antimicrob Agents Chemother. 1990;34:14636.PubMedGoogle Scholar
  43. Pasatiempo  AMG, Kroser  JA, Rudnick  M, Hoffman  BI. Acute renal failure after intravenous immunoglobulin therapy. J Rheumatol. 1994;21:3479.PubMedGoogle Scholar
  44. Sekul  EA, Cupler  EJ, Dalakas  MC. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy: frequency and risk factors. Ann Intern Med. 1994;121:25962.PubMedGoogle Scholar
  45. Wolff  SN, Fay  JW, Herzig  RH, Greer  JP, Dummer  S, Brown  RA, High-dose weekly intravenous immunoglobulin to prevent infections in patients undergoing autologous bone marrow transplantation orsevere myelosuppressive therapy. Ann Intern Med. 1993;118:93742.PubMedGoogle Scholar
  46. Bullowa  JGM. The management of the pneumonias. New York:Oxford University Press, 1937.
  47. Bullowa  JGM. The reliability of sputum typing and its relation to serum therapy. JAMA. 1935;105:15128.
  48. Sadziene  A, Rosa  PA, Thompson  PA, Hogan  DM, Barbour  AG. Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization. J Exp Med. 1992;176:799809. DOIPubMedGoogle Scholar
  49. Halter  R, Pohlner  J, Meyer  TF. Mossaic-like organization of IgA protease genes in Neisseria gonorrhoeae generated by horizontal genetic exchange in vivo. EMBO J. 1989;8:273744.PubMedGoogle Scholar
  50. Barnes  GL, Doyle  LW, Hewson  PH, A randomised trial of oral gammaglobulin in low-birth-weight infants infected with rotavirus. Lancet. 1982;1:13713. DOIPubMedGoogle Scholar
  51. Borowitz  SM, Saulsbury  FT. Treatment of chronic cryptosporidial infection with orally admininstered human serum immune globulin. J Pediatr. 1991;119:5935. DOIPubMedGoogle Scholar
  52. Schroff  RW, Foon  KA, Beatty  SM, Oldham  RK, Morgan  AC. Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res. 1985;45:87985.PubMedGoogle Scholar
  53. Lazarovits  AI, Rochon  J, Banks  L, Hollomby  DJ, Muirhead  N, Jevnikar  AM, . Human mouse chimeric CD7 monoclonal antibody (SDZCHH380) for the prophylaxis of kidney transplant rejection. J Immunol. 1993;150:516374.PubMedGoogle Scholar
  54. Issacs  JD, Watts  RA, Hazleman  BL, Hale  G, Keogan  MT, Cobbold  SP, Humanized monoclonal antibody therapy for rheumatoid arthritis. Lancet. 1992;340:74852. DOIPubMedGoogle Scholar
  55. Hoyne  AL. Intravenous treatment of meningococcic meningitis with meningococcus antitoxin. JAMA. 1936;107:47881.
  56. Flexner  S. The results of the serum treatment in thirteen hundred cases of epidemic meningitis. J Exp Med. 1913;17:553. DOIPubMedGoogle Scholar
  57. Triguro  D, Buciak  JB, Yang  J, Pardridge  WM. Blood-brain barrier transport of cationized immunoglobulin G: enhanced delivery compared to native protein. Proc Natl Acad Sci U S A. 1989;86:47615. DOIPubMedGoogle Scholar
  58. Friden  PM, Walus  LR, Musso  GF, Taylor  MA, Malfroy  B, Starzyk  RM. Anti-transferrin receptor antibody and antibody-drug complexes cross the blood-brain barrier. Proc Natl Acad Sci U S A. 1991;88:47715. DOIPubMedGoogle Scholar
  59. Conti  DJ, Freed  BM, Gruber  SA, Lempert  N. Prophylaxis of primary cytomegalovirus disease in renal transplant recipients. Arch Surg. 1994;129:4437.PubMedGoogle Scholar
  60. Wolff  SM. Monoclonal antibodies and the treatment of gram-negative bacteremia and shock. N Engl J Med. 1991;324:4867.PubMedGoogle Scholar
  61. Fink  MP. Adoptive immunotherapy of gram-negative sepsis:use of monoclonal antibodies to lipopolysaccharide. Crit Care Med. 1994;21:S329.
  62. Loewenthal  L, Berlin  MD. Combined serum and sulphanilamide in the treatment of streptococcal infections in mice. Lancet. 1939;1:1979. DOIGoogle Scholar
  63. Klemperer  G, Klemperer  F. Versuche uber immunisirung und heilung bei der pneumokokkeninfection. Berl Klin Wochenschr. 1891;28:8335.
  64. Bullowa  JGM. Serum therapy. In: The management of the pneumonias, New York: Oxford University Press, 1937:283-362.
  65. Watson  DA, Musher  DM, Jacobson  JW, Verhoef  J. A brief history of the pneumococcus in biomedical research: a panoply of scientific discovery. Clin Infect Dis. 1993;17:91324.PubMedGoogle Scholar
  66. Devi  SJN, Schneerson  R, Egan  W, Ulrich  TJ, Bryla  D, Robbins  JB, Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity. Infect Immun. 1991;59:37007.PubMedGoogle Scholar
  67. Mukherjee  J, Scharff  MD, Casadevall  A. Protective murine monoclonal antibodies to Cryptococcus neoformans. Infect Immun. 1992;60:453441.PubMedGoogle Scholar
  68. Pier  GB, Thomas  D, Small  G, Siadak  A, Zweerink  H. In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeroginosa lipopolysaccharide. Infect Immun. 1989;57:1749.PubMedGoogle Scholar

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