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Volume 5, Number 1—February 1999
Synopsis

Using Monoclonal Antibodies to Prevent Mucosal Transmission of Epidemic Infectious Diseases

Larry Zeitlin*, Richard A. Cone*†, and Kevin J. Whaley*†Comments to Author 
Author affiliations: *ReProtect, LLC, Baltimore, Maryland, USA; †The Johns Hopkins University, Baltimore, Maryland, USA

Main Article

Table 2

Examples of highly effective topical passive immunization of mucosa

Pathogen Speciesa Routeb Anti-bodyc Prevention Ref.
Viruses
Herpes simplex mou v m 100% (64, 65)
r m 100% (66)
Influenza fer o p 100% (67)
mou n p > 4d (68)
Rotavirus hum o p 100% (69, 70)
Respiratory syncytial mon n m 3-4d (71)
Bacteria
Chlamydia trachomatis mou v m 90% (72)
Clostridium difficule ham o p 100% (73)
Escherichia coli hum o p 100% (74)
Porphyromonas gingivalis hum o m 100% (75)
Shigella flexneri hum o p 100% (76)
Staphylococcus aureus mou n p 3-4e (77)
Streptococcus mutans hum o m 100% (78)
Vibrio cholerae mou o m 100% (79)
Fungi
Candida albicans mou v p >50f (80)
Parasites
Cryptosporidium parvum mou o m 77g (81)

aSpecies tested in: mou=mouse; fer=ferret; hum=human; mon=monkey; ham=hamster.
bDelivery route of pathogen and antibody: v=vaginal; r=rectal; o=oral; n=nasal.
cAntibody: m=monoclonal; p=polyclonal.
d log10 reduction in virus titer.
e log10 reduction in cfu.
f % reduction in cfu.
g % reduction in number of parasites.

Main Article

References
  1. Kohler  G, Milstein  C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–7. DOIPubMedGoogle Scholar
  2. Casadevall  A, Scharff  M. Return to the past: the case for antibody-based therapies in infectious diseases. Clin Infect Dis. 1995;21:150–61.PubMedGoogle Scholar
  3. Casadevall  A. Antibody-based therapies for emerging infectious diseases. Emerg Infect Dis. 1996;2:200–8. DOIPubMedGoogle Scholar
  4. Cross  A. Intravenous immunoglobulins to prevent and treat infectious diseases. In: Atassi MZ, GS Bixler GSJ, editors. Immunobiology of proteins and peptides VIII. New York: Plenum Press; 1995.
  5. Lederberg  J, Shope  R, Oaks  S. Emerging Infections. Washington: National Academy Press; 1992.
  6. Mims  C, Dimmock  N, Nash  A, Stephen  J. Mims' pathogenesis of infectious disease. 4th ed. San Diego: Academic Press; 1995.
  7. Mo  H, Stamatatos  L, Ip  JE, Barbas  CF, Parren  PWHI, Burton  DR, Human immunodeficiency virus type 1 mutants that escape neutralization by human monoclonal antibody IgG1b12. J Virol. 1997;71:6869–74.PubMedGoogle Scholar
  8. Mandrell  RE, Apicella  MA. Lipo-oligosaccharides (LOS) of mucosal pathogens: molecular mimicry and host-modification of LOS. Immunobiology. 1993;187:382–402.PubMedGoogle Scholar
  9. Anderson  D, Yunis  E. "Trojan horse" leukocytes in AIDS. N Engl J Med. 1983;309:984–5.
  10. Ogra  P. Mucosal immunoprophylaxis: an introductory overview. In: Kiyono H, Ogra P, McGhee J, editors. Mucosal vaccines. New York: Academic Press; 1996. p. 1-14.
  11. Cone  RA, Whaley  KJ. Monoclonal antibodies for reproductive health: Part I. Preventing sexual transmission of disease and pregnancy with topically applied antibodies. Am J Reprod Immunol. 1994;32:114–31.PubMedGoogle Scholar
  12. Saltzman  WM. Antibodies for treating and preventing disease: the potential role of polymeric controlled release. Crit Rev Ther Drug Carrier Syst. 1993;10:111–42.PubMedGoogle Scholar
  13. Silverstein  A. History of immunology. In: Paul W, editor. Fundamental immunology. 2nd ed. New York: Raven Press Ltd.; 1989.
  14. Dimmock  N. Neutralization of animal viruses. Curr Top Microbiol Immunol. 1993;183:1–149.PubMedGoogle Scholar
  15. Igarashi  A, Fukuoka  T, Fukai  K. Passive immunization of mice with rabbit antisera against Chikungunya virus and its components. Biken J. 1971;14:353–5.PubMedGoogle Scholar
  16. CytoGam package insert. Gaithersburg (MD): MedImmune Inc.
  17. Men  RH, Bray  M, Lai  CJ. Carboxy-terminally truncated dengue virus envelope glycoproteins expressed on the cell surface and secreted extracellularly exhibit increased immunogenicity in mice. J Virol. 1991;65:1400–7.PubMedGoogle Scholar
  18. Mikhailov  VV, Borisevich  IV, Chernikova  NK, Potryvaeva  NV, Krasnianskii  VP. The evaluation in hamadryas baboons of the possibility for the specific prevention of Ebola fever. Vopr Virusol. 1994;39:82–4.PubMedGoogle Scholar
  19. Arikawa  J, Yao  JS, Yoshimatsu  K, Takashima  I, Hashimoto  N. Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies. Arch Virol. 1992;126:271–81. DOIPubMedGoogle Scholar
  20. Eis-Hübinger  A, Schmidt  D, Schneweis  K. Anti-glycoprotein B monoclonal antibody protects mice against genital herpes simplex virus infection by inhibition of virus replication at the inoculated mucous membranes. J Gen Virol. 1993;74:379–85. DOIPubMedGoogle Scholar
  21. Atherton  SS. Protection from retinal necrosis by passive transfer of monoclonal antibody specific for herpes simplex virus glycoprotein D. Curr Eye Res. 1992;11:45–52. DOIPubMedGoogle Scholar
  22. Safrit  JT, Fung  MS, Andrews  CA, Braun  DG, Sun  WN, Chang  TW, hu-PBL-SCID mice can be protected from HIV-1 infection by passive transfer of monoclonal antibody to the principal neutralizing determinant of envelope gp120. AIDS. 1993;7:15–21. DOIPubMedGoogle Scholar
  23. Stapleton  JT. Passive immunization against hepatitis A. Vaccine. 1992;10:S45–7. DOIPubMedGoogle Scholar
  24. McGory  RW, Ishitani  MB, Oliveira  WM, Stevenson  WC, McCullough  CS, Dickson  RC, Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis with aggressive passive immunization. Transplantation. 1996;61:1358–64. DOIPubMedGoogle Scholar
  25. Okuno  Y, Matsumoto  K, Isegawa  Y, Ueda  S. Protection against the mouse-adapted A/FM/1/47 strain of influenza A virus in mice by a monoclonal antibody with cross-neutralizing activity among H1 and H2 strains. J Virol. 1994;68:517–20.PubMedGoogle Scholar
  26. Jahrling  PB, Peters  CJ. Passive antibody therapy of Lassa fever in cynomolgus monkeys: importance of neutralizing antibody and Lassa virus strain. Infect Immun. 1984;44:528–33.PubMedGoogle Scholar
  27. Giraudon  P, Wild  T. Correlation between epitopes on hemagglutinin of measles virus and biological activities: passive protection by monoclonal antibodies is related to their hemagglutination inhibiting activity. Virology. 1985;144:46–58. DOIPubMedGoogle Scholar
  28. Chanock  R, Crowe  J, Murphy  B, Burron  D. Human monoclonal antibody Fab fragments cloned from combinatorial libraries: potential usefulness in prevention and/or treatment of major human viral diseases. Infect Agents Dis. 1993;2:118–31.PubMedGoogle Scholar
  29. Dietzschold  B, Kao  M, Zheng  YM, Chen  ZY, Maul  G, Fu  ZF, Delineation of putative mechanisms involved in antibody-mediated clearance of rabies virus from the central nervous system [published erratum appears in Proc Natl Acad Sci U S A 1992;89:9365]. Proc Natl Acad Sci U S A 1992;89:7252-6. 630.
  30. Sherry  B, Li  XY, Tyler  KL, Cullen  JM, Virgin  HW IV. Lymphocytes protect against and are not required for reovirus-induced myocarditis. J Virol. 1993;67:6119–24.PubMedGoogle Scholar
  31. Niklasson  BS, Meadors  GF, Peters  CJ. Active and passive immunization against Rift Valley fever virus infection in Syrian hamsters. APMIS. 1984;92:197–200.
  32. MedImmune reports fourth set of clinical results evaluating MEDI-493 [press release]. Gaithersburg (MD): MedImmune; May 6, 1997.
  33. The PREVENT Study Group. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics. 1997;99:93–9. DOIPubMedGoogle Scholar
  34. Neumann-Haefelin  D, Neumann-Haefelin  C, Petersen  EE, Luthardt  T, Hass  R. Passive immunization against rubella: studies on the effectiveness of rubella-immuno-globulin after intranasal infection with rubella vaccination virus. Dtsch Med Wochenschr. 1975;100:177–81. DOIPubMedGoogle Scholar
  35. Brunell  P, Ross  A, Miller  L. B K. Prevention of varicella by zoster immune globulin. N Engl J Med. 1969;280:1191–4.PubMedGoogle Scholar
  36. Danes  L, Hruskova  J. Efficiency testing of passive immunization against Venezuelan equine encephalomyelitis in mice. Acta Virol. 1969;13:554–6.PubMedGoogle Scholar
  37. Johnson  RC, Kodner  C, Russell  M. Passive immunization of hamsters against experimental infection with the Lyme disease spirochete. Infect Immun. 1986;53:713–4.PubMedGoogle Scholar
  38. Sato  Y, Sato  H. Further characterization of Japanese acellular pertussis vaccine prepared in 1988 by 6 Japanese manufacturers. Tokai J Exp Clin Med. 1988;13:79–88.PubMedGoogle Scholar
  39. Kaukoranta-Tolvanen  SE, Laurila  AL, Saikku  P, Leinonen  M, Laitinen  K. Experimental Chlamydia pneumoniae infection in mice: effect of reinfection and passive immunization. Microb Pathog. 1995;18:279–88. DOIPubMedGoogle Scholar
  40. Cotter  TW, Meng  Q, Shen  ZL, Zhang  YX, Su  H, Caldwell  HD. Protective efficacy of major outer membrane protein-specific immunoglobulin A (IgA) and IgG monoclonal antibodies in a murine model of Chlamydia trachomatis genital tract infection. Infect Immun. 1995;63:4704–14.PubMedGoogle Scholar
  41. Raff  HV, Bradley  C, Brady  W, Donaldson  K, Lipsich  L, Maloney  G, Comparison of functional activities between IgG1 and IgM class-switched human monoclonal antibodies reactive with group B streptococci or Escherichia coli K1. J Infect Dis. 1991;163:346–54.PubMedGoogle Scholar
  42. Drabick  J, Narayanan  R, Williams  J, LeDuc  J, Nacy  C. Passive protection of mice against lethal Francisella tularensis (live tularemia vaccine strain) infection by the sera of human recipients of the live tularemia vaccine. Am J Med Sci. 1994;308:83–7. DOIPubMedGoogle Scholar
  43. Shigeoka  AO, Pincus  SH, Rote  NS, Hill  HR. Protective efficacy of hybridoma type-specific antibody against experimental infection with group-B Streptococcus. J Infect Dis. 1984;149:363–72.PubMedGoogle Scholar
  44. Schreiber  JR, Barrus  V, Cates  KL, Siber  GR. Functional characterization of human IgG, IgM, and IgA antibody directed to the capsule of Haemophilus influenzae type B. J Infect Dis. 1986;153:8–16.PubMedGoogle Scholar
  45. Hayatsu  E, Kawakubo  Y, Yayoshi  M, Araake  M, Wakai  M, Yoshida  A, Immunological responses of hamsters in the acquired immune state to Mycoplasma pneumoniae infection. Microbiol Immunol. 1981;25:1255–63.PubMedGoogle Scholar
  46. Brodeur  BR, Larose  Y, Tsang  P, Hamel  J, Ashton  F, Ryan  A. Protection against infection with Neisseria meningitidis group B serotype 2b by passive immunization with serotype-specific monoclonal antibody. Infect Immun. 1985;50:510–6.PubMedGoogle Scholar
  47. Harmon  RC, Rutherford  RL, Wu  HM, Collins  MS. Monoclonal antibody-mediated protection and neutralization of motility in experimental Proteus mirabilis infection. Infect Immun. 1989;57:1936–41.PubMedGoogle Scholar
  48. Fisher  MW. A polyvalent human gamma-globulin immune to Pseudomonas aeruginosa: passive protection of mice against lethal infection. J Infect Dis. 1977;136:S181–5.PubMedGoogle Scholar
  49. Svenson  SB, Nurminen  M, Lindberg  AA. Artificial Salmonella vaccines: O-antigenic oligosaccharide-protein conjugates induce protection against infection with Salmonella typhimurium. Infect Immun. 1979;25:863–72.PubMedGoogle Scholar
  50. Adamus  G, Mulczyk  M, Witkowska  D, Romanowska  E. Protection against keratoconjunctivitis shigellosa induced by immunization with outer membrane proteins of Shigella spp. Infect Immun. 1980;30:321–4.PubMedGoogle Scholar
  51. Scott  DF, Best  GK, Kling  JM, Thompson  MR, Adinolfi  LE, Bonventre  PF. Passive protection of rabbits infected with toxic shock syndrome-associated strains of Staphylococcus aureus by monoclonal antibody to toxic shock syndrome toxin 1. Reviews of Infectious Diseases 1989;11:S214-7; discussion S217-8.
  52. Swendsen  CL, Johnson  W. Humoral immunity to Streptococcus pneumoniae induced by a pneumococcal ribosomal protein fraction. Infect Immun. 1976;14:345–54.PubMedGoogle Scholar
  53. Azadegan  AA, Schell  RF, LeFrock  JL. Immune serum confers protection against syphilitic infection on hamsters. Infect Immun. 1983;42:42–7.PubMedGoogle Scholar
  54. Motin  V, Nakajima  R, Smirnov  G, Brubaker  R. Passive immunity to Yersiniae mediated by anti-recombinant V antigen and protein A-V antigen fusion peptide. Infect Immun. 1994;62:4192–201.PubMedGoogle Scholar
  55. Friedlander  AM, Welkos  SL, Worsham  PL, Andrews  GP, Heath  DG, Anderson  GW Jr, Relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis. Clin Infect Dis. 1995;21:S178–81.PubMedGoogle Scholar
  56. Tavares  D, Ferreira  P, Vilanova  M, Videira  A, Arala-Chaves  M. Immunoprotection against systemic candidiasis in mice. Int Immunol. 1995;7:785–96. DOIPubMedGoogle Scholar
  57. Nussbaum  G, Yuan  R, Casadevall  A, Scharff  MD. Immunoglobulin G3 blocking antibodies to the fungal pathogen Cryptococcus neoformans. J Exp Med. 1996;183:1905–9. DOIPubMedGoogle Scholar
  58. Diggs  CL, Hines  F, Wellde  BT. Plasmodium falciparum: passive immunization of Aotus lemurinus griseimembra with immune serum. Exp Parasitol. 1995;80:291–6. DOIPubMedGoogle Scholar
  59. Johnson  AM, McDonald  PJ, Neoh  SH. Monoclonal antibodies to Toxoplasma cell membrane surface antigens protect mice from toxoplasmosis. J Protozool. 1983;30:351–6.PubMedGoogle Scholar
  60. Garrett  L. The coming plague. New York: Penguin Books; 1995.
  61. Kraehenbuhl  JP, Neutra  MR. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev. 1992;72:853–79.PubMedGoogle Scholar
  62. Cone  R. Mucus. In: Ogra PL, Mestecky J, Lamm ME, Strober W, McGhee JR, Bienenstock J, editors. Mucosal immunology. 2nd ed. New York: Academic Press; 1999.
  63. Lamm  M. Interaction of antigens and antibodies at mucosal surfaces. Annu Rev Microbiol. 1997;51:311–40. DOIPubMedGoogle Scholar
  64. Whaley  KJ, Zeitlin  L, Barratt  RA, Hoen  TE, Cone  RA. Passive immunization of the vagina protects mice against vaginal transmission of genital herpes infections. J Infect Dis. 1994;169:647–9.PubMedGoogle Scholar
  65. Zeitlin  L, Whaley  KJ, Sanna  PP, Moench  TR, Bastidas  R, De Logu  A, Topically applied human recombinant monoclonal IgG1 antibody and its Fab and F(ab')2 fragments protect mice from vaginal transmission of HSV-2. Virology. 1996;225:213–5. DOIPubMedGoogle Scholar
  66. Zeitlin  L. Topical methods for preventing genital herpes infection in the mouse. Reproductive biology. [dissertation]. Baltimore: The Johns Hopkins University; 1996.
  67. Jakeman  K, Smith  H, Sweet  C. Mechanism of immunity to influenza: maternal and passive neonatal protection following immunization of adult ferrets with a live vaccinia-influenza virus hemagglutinin recombinant but not with recombinants containing other influenza virus proteins. J Gen Virol. 1989;70:1523–31. DOIPubMedGoogle Scholar
  68. Tamura  S, Funato  H, Hirabayashi  Y, Suzuki  Y, Nagamine  T, Aizawa  C, Cross-protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules. Eur J Immunol. 1991;21:1337–44. DOIPubMedGoogle Scholar
  69. Davidson  GP, Whyte  PB, Daniels  E, Franklin  K, Nunan  H, McCloud  PI, Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus [see comments]. Lancet. 1989;2:709–12. DOIPubMedGoogle Scholar
  70. Ebina  T. Prophylaxis of rotavirus gastroenteritis using immunoglobulin. Arch Virol Suppl. 1996;12:217–23.PubMedGoogle Scholar
  71. Weltzin  R, Traina-Dorge  V, Soike  K, Zhang  JY, Mack  P, Soman  G, Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection. J Infect Dis. 1996;174:256–61.PubMedGoogle Scholar
  72. Peterson  EM, Cheng  X, Motin  VL, de la Maza  LM. Effect of immunoglobulin G isotype on the infectivity of Chlamydia trachomatis in a mouse model of intravaginal infection. Infect Immun. 1997;65:2693–9.PubMedGoogle Scholar
  73. Lyerly  DM, Bostwick  EF, Binion  SB, Wilkins  TD. Passive immunization of hamsters against disease caused by Clostridium difficile by use of bovine immunoglobulin G concentrate. Infect Immun. 1991;59:2215–8.PubMedGoogle Scholar
  74. Tacket  CO, Losonsky  G, Link  H, Hoang  Y, Guesry  P, Hilpert  H, Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. N Engl J Med. 1988;318:1240–3.PubMedGoogle Scholar
  75. Booth  V, Ashley  F, Lehner  T. Passive immunization with monoclonal antibodies against Porphyromonas gingivalis in patients with periodontitis. Infect Immun. 1996;64:422–7.PubMedGoogle Scholar
  76. Tacket  C, Binion  S, Bostwick  E, Losonsky  G, Roy  M, Edelman  R. Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. Am J Trop Med Hyg. 1992;47:276–83.PubMedGoogle Scholar
  77. Ramisse  F, Szatanik  M, Binder  P, Alonso  J-M. Passive local immunotherapy of experimental staphylococcal pneumonia with human intravenous immunoglobulin. J Infect Dis. 1993;168:1030–3.PubMedGoogle Scholar
  78. Ma  JK, Hunjan  M, Smith  R, Kelly  C, Lehner  T. An investigation into the mechanism of protection by local passive immunization with monoclonal antibodies against Streptococcus mutans. Infect Immun. 1990;58:3407–14.PubMedGoogle Scholar
  79. Apter  FM, Michetti  P, Winner  LSD, Mack  JA, Mekalanos  JJ, Neutra  MR. Analysis of the roles of antilipopolysaccharide and anti-cholera toxin immunoglobulin A (IgA) antibodies in protection against Vibrio cholerae and cholera toxin by use of monoclonal IgA antibodies in vivo. Infect Immun. 1993;61:5279–85.PubMedGoogle Scholar
  80. Cassone  A, Boccanera  M, Adriani  D, Santoni  G, De Bernardis  F. Rats clearing a vaginal infection by Candida albicans acquire specific, antibody-mediated resistance to vaginal reinfection. Infect Immun. 1995;63:2619–24.PubMedGoogle Scholar
  81. Perryman  LE, Riggs  MW, Mason  PH, Fayer  R. Kinetics of Crytosporidium parvum sporozoite neutralization by monoclonal antibodies, immune bovine serum, and immune bovine colostrum. Infect Immun. 1990;58:257–9.PubMedGoogle Scholar
  82. Ma  JK, Hein  MB. Immunotherapeutic potential of antibodies produced in plants. Trends Biotechnol. 1995;13:522–7. DOIPubMedGoogle Scholar
  83. Chintalacharuvu  KR, Morrison  SL. Production of secretory immunoglobulin A by a single mammalian cell. Proc Natl Acad Sci U S A. 1997;94:6364–8. DOIPubMedGoogle Scholar
  84. Kilian  M, Russel  M. Function of mucosal immunoglobulins. In: Ogra P, Mestecky J, Lamm M, Strober W, McGhee J, Bienenstock J, editors. Handbook of mucosal immunology. San Diego: Academic Press; 1994. p. 127-37.
  85. Kraehenbuhl  JP, Neutra  MR. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev. 1992;72:853–79.PubMedGoogle Scholar
  86. Winter  G, Griffiths  A, Hawkins  R, Hoogenboom  H. Making antibodies by phage display technology. Annu Rev Immunol. 1994;12:433–55. DOIPubMedGoogle Scholar
  87. Burton  D, Barbas  C. Human antibodies from combinatorial libraries. Adv Immunol. 1994;57:191–280. DOIPubMedGoogle Scholar
  88. Williamson  R, Burioni  R, Sanna  P, Partridge  L, Barbas  C, Burton  D. Human monoclonal antibodies against a plethora of viral pathogens from single combinatorial libraries. Proc Natl Acad Sci U S A. 1993;90:4141–5. DOIPubMedGoogle Scholar
  89. Vaughan  T, Williams  A, Pritchard  K, Osbourn  J, Pope  A, Earnshaw  J, Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol. 1996;14:309–14. DOIPubMedGoogle Scholar
  90. Green  LL, Hardy  MC, Maynard-Currie  CE, Tsuda  H, Louie  DM, Mendez  MJ, Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs. Nat Genet. 1994;7:13–21. DOIPubMedGoogle Scholar
  91. Mendez  MJ, Green  LL, Corvalan  JR, Jia  XC, Maynard-Currie  CE, Yang  XD, Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice. Nat Genet. 1997;15:146–56. DOIPubMedGoogle Scholar
  92. Sherman-Gold  R. Monoclonal antibodies: the evolution from '80s magic bullets to mature, mainstream applications as clinical therapeutics. Genetic Engineering News 1997:17.
  93. Vaughan  TJ, Osbourn  JK, Tempest  PR. Human antibodies by design. Nat Biotechnol. 1998;16:535–9. DOIPubMedGoogle Scholar
  94. Barbas  C, Hu  D, Dunlop  N, Sawyer  L, Cababa  D, Hendry  R, In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity. Proc Natl Acad Sci U S A. 1994;91:3809–13. DOIPubMedGoogle Scholar
  95. Barbas  CF, Burton  DR. Selection and evolution of high-affinity human anti-viral antibodies. Trends Biotechnol. 1996;14:230–4. DOIPubMedGoogle Scholar
  96. Crothers  D, Metzger  H. The influence of polyvalency on the binding properties of antibodies. Immunochemistry. 1972;9:341–57. DOIPubMedGoogle Scholar
  97. Sherwood  JK, Zeitlin  L, Chen  X, Whaley  KJ, Cone  RA, Saltzman  WM. Residence half-life of IgG administered topically to the mouse vagina. Biol Reprod. 1996;54:264–9. DOIPubMedGoogle Scholar
  98. Glassy  M. Production: the rate-limiting step in obtaining human monoclonal antibody pharmaceuticals. In: Monoclonal antibody production. La Jolla (CA): International Business Communications; 1996.
  99. DeYoung  G. Monoclonal Ab processors/manufacturers stress costs and productivity. Genetic Engineering News 1996:8.
  100. Hiatt  A, Caffertey  R, Bowdish  K. Production of antibodies in transgenic plants. Nature. 1989;342:76–8. DOIPubMedGoogle Scholar
  101. Genzyme transgenic manufactures monoclonal antibody in goats' milk [press release]. Cambridge (MA): Genzyme; May, 1995.
  102. Hiatt  A. Antibodies produced in plants. Nature. 1990;344:469–70. DOIPubMedGoogle Scholar
  103. Seaver  S. Monoclonal antibodies: using new techniques to reduce development time. Genetic Engineering News 1997:13.
  104. Food and Drug Administration. International conference on harmonisation; guidance on preclinical safety evaluation of biotechnology-derived pharmaceuticals; availablity. Fed Regist. 1997;62:61515–9.
  105. OraVax Reports Results from Phase III Trial of HNK20 Nosedrop for Respiratory Syncytial Virus in Infants [press release]. Cambridge (MA): OraVax; March 19, 1997.
  106. Ma  J, Smith  R, Lehner  T. Use of monoclonal antibodies in local passive immunization to prevent colonization of human teeth by Streptococcus mutans. Infect Immun. 1987;55:1274–8.PubMedGoogle Scholar
  107. Beck  L, Boots  L, Stevens  V. Absorption of antibodies from the baboon vagina. Biol Reprod. 1975;13:10–6. DOIPubMedGoogle Scholar
  108. Corthesy  B, Kaufmann  M, Phalipon  A, Peitsch  M, Neutra  M, Kraehenbuhl  J-P. A pathogen-specific epitope inserted into recombinant secretory immunoglobulin A is immunogenic by the oral route. J Biol Chem. 1996;271:33670–7. DOIPubMedGoogle Scholar
  109. Tsume  Y, Taki  Y, Sakane  T, Nadai  T, Sezaki  H, Watabe  K, Quantitative evaluation of the gastrointestinal absorption of protein into the blood and lymph circulation. Biol Pharm Bull. 1996;19:1332–7.PubMedGoogle Scholar
  110. Kuo  PY, Sherwood  JK, Saltzman  WM. Topical antibody delivery systems produce sustained levels in mucosal tissue and blood. Nat Biotechnol. 1998;16:163–7. DOIPubMedGoogle Scholar
  111. Points to consider in the manufacture and testing of monoclonal antibody products for human use. Washington: U.S. Department of Health and Human Services, Food and Drug Administration; 1997.
  112. Ma  JK, Hein  MB. Plant antibodies for immunotherapy. Plant Physiol. 1995;109:341–6. DOIPubMedGoogle Scholar
  113. Ma  JK, Hikmat  BY, Wycoff  K, Vine  ND, Chargelegue  D, Yu  L, Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med. 1998;4:601–6. DOIPubMedGoogle Scholar
  114. Mo  H, Stamatatos  L, Ip  J, Barbas  C, Parren  P, Burton  D, Human immunodeficiency virus type 1 mutants that escape neutralization by human monoclonal antibody IgG1b12. J Virol. 1997;71:6869–74.PubMedGoogle Scholar
  115. Babcook  JS, Leslie  KB, Olsen  OA, Salmon  RA, Schrader  JW. A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities. Proc Natl Acad Sci U S A. 1996;93:7843–8. DOIPubMedGoogle Scholar
  116. Murray  C, Lopez  A. Global and regional cause-of-death patterns in 1990. In: Murray C, Lopez A, editors. Global comparative assessments in the health sector. Geneva: World Health Organization; 1994. p. 21-54.
  117. Eng  T, Butler  W. The hidden epidemic. Institute of Medicine. Washington: National Academy Press; 1997.
  118. Bogstedt  A, Johansen  K, Hatta  H, Kim  M, Casswall  T, Svensson  L, Passive immunity against diarrhoea. Acta Paediatr. 1996;85:125–8. DOIPubMedGoogle Scholar
  119. Eibl  M, Wolf  H, Furnkranz  H, Rosenkranz  A. Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA-IgA feeding. N Engl J Med. 1988;319:1–7.PubMedGoogle Scholar
  120. Petschow  B, Talbott  R. Reduction in virus-neutralizing activity of a bovine colostrum immunoglobulin concentrate by gastric acid and digestive enzymes. J Pediatr Gastroenterol Nutr. 1994;19:228–35. DOIPubMedGoogle Scholar
  121. Ogra  P, Fishaut  M. Human breast milk. In: Remington J, Klein J, editors. Infectious diseases of the fetus and newborn infant. 3rd ed. Philadelphia: W.B. Saunders Company; 1990. p. 68-84.
  122. Prince  G, Hemming  V, Horswood  R, Baron  P, Chanock  R. Effectiveness of topically administered neutralizing antibodies in experimental immunotherapy of respiratory syncytial virus infection in cotton rats. J Virol. 1987;61:1851–4.PubMedGoogle Scholar
  123. Radomsky  ML, Whaley  KJ, Cone  RA, Saltzman  WM. Controlled vaginal delivery of antibodies in the mouse. Biol Reprod. 1992;47:133–40. DOIPubMedGoogle Scholar
  124. Sherwood  J, Zeitlin  L, Whaley  K, Cone  R, Saltzman  W. Controlled release of antibodies for long-term topical passive immunoprotection of female mice against genital herpes. Nat Biotechnol. 1996;14:468–71. DOIPubMedGoogle Scholar
  125. Tjokronegoro  A, Sirisinha  S. Degradation of immunoglobulins by secretions of human reproductive tracts. J Reprod Fertil. 1974;38:221–4. DOIPubMedGoogle Scholar
  126. O'Hara  M. Ophthalmia neonatorum. Pediatr Clin North Am. 1993;40:715–25.PubMedGoogle Scholar
  127. Singh  M, Sugathan  PS, Bhujwala  RA. Human colostrum for prophylaxis against sticky eyes and conjunctivitis in the newborn. J Trop Pediatr. 1982;28:35–7.PubMedGoogle Scholar

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