Skip to main content
NCBI home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2019 Dec 11;84(4):660–666. doi: 10.1093/ps/84.4.660

Antibodies: an alternative for antibiotics?

LR Berghman *,†,1, D Abi-Ghanem *, SD Waghela †, SC Ricke *,†
PMCID: PMC7107177  PMID: 15844826

Abstract

In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that “it was time to close the books on infectious diseases.” We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as “serum therapy,” the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and “molecular farming of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases.

Key words: recombinant antibody, plant, alternative, antibiotic, expression system

REFERENCES

  1. Almeida C.M., Kanashiro M.M., Rangel Filho F.B., Mata M.F., Kipnis T.L., da Silva. W.D. Development of snake antivenom antibodies in chickens and their purification from yolk. Vet. Rec. 1998;143:579–584. doi: 10.1136/vr.143.21.579. [DOI] [PubMed] [Google Scholar]
  2. Baldry P.E. The Battle Against Bacteria: A History of the Development of Antibacterial Drugs for the General Reader. Cambridge University Press; Cambridge, UK: 1965. [Google Scholar]
  3. Barrington G.M., Parish. S.M. Bovine neonatal immunology. Vet. Clin. North Am. Food Anim. Pract. 2001;17:463–476. doi: 10.1016/S0749-0720(15)30001-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Behring E., Kitasako. S. Ueber das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren. Dtsch. Med. Wochenschr. 1890;16:1113–1114. [PubMed] [Google Scholar]
  5. Bird R.E., Hardman K.D., Jacobson J.W., Johnson S., Kaufman B.M., Lee S.M., Lee T., Pope S.H., Riordan G.S., Whitlow. M. Single-chain antigen-binding proteins. Science. 1988;242:423–426. doi: 10.1126/science.3140379. [DOI] [PubMed] [Google Scholar]
  6. Buchwald U.K., Pirofski. L. Immune therapy for infectious diseases at the dawn of the 21st century: The past, present and future role of antibody therapy, therapeutic vaccination and biological response modifiers. Curr. Pharm. Des. 2003;9:945–968. doi: 10.2174/1381612033455189. [DOI] [PubMed] [Google Scholar]
  7. Carlander D., Kollberg H., Larsson. A. Retention of specific yolk IgY in the human oral cavity. BioDrugs. 2002;16:433–437. doi: 10.2165/00063030-200216060-00004. [DOI] [PubMed] [Google Scholar]
  8. Carlander D., Kollberg H., Wejaker P.E., Larsson. A. Peroral immunotherapy with yolk antibodies for the prevention and treatment of enteric infections. Immunol. Res. 2000;21:1–6. doi: 10.1385/IR:21:1:1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carroll S.B., Thalley B.S., Theakston R.D., Laing. G. Comparison of the purity and efficacy of affinity purified avian antivenoms with commercial equine crotalid antivenoms. Toxicon. 1992;30:1017–1025. doi: 10.1016/0041-0101(92)90046-8. [DOI] [PubMed] [Google Scholar]
  10. Casadevall A. Antibody-based therapies for emerging infectious diseases. Emerg. Infect. Dis. 1996;2:200–208. doi: 10.3201/eid0203.960306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Casadevall A., Scharff. M.D. Serum therapy revisited: Animal models of infection and development of passive antibody therapy. Antimicrob. Agents Chemother. 1994;38:1695–1702. doi: 10.1128/aac.38.8.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Casalvilla R., Duenas M., Ayala M., Cruz S., Cruz L., Buurman W.A., Gavilondo. J.V. A bacterial single-chain Fv antibody fragment that inhibits binding of its parental anti-E-selectin monoclonal antibody to activated human endothelial cells. J. Biotechnol. 1999;72:1–12. doi: 10.1016/s0168-1656(99)00005-x. [DOI] [PubMed] [Google Scholar]
  13. Cirino N.M., Sblattero D., Allen D., Peterson S.R., Marks J.D., Jackson P.J., Bradbury A., Lehnert. B.E. Disruption of anthrax toxin binding with the use of human antibodies and competitive inhibitors. Infect. Immun. 1999;67:2957–2963. doi: 10.1128/iai.67.6.2957-2963.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Conn H.W., Conn H.J., editors. Bacteriology. Williams and Wilkins Co.; Baltimore, MD: 1929. [Google Scholar]
  15. Davidson G.P., Whyte P.B., Daniels E., Franklin K., Nunan H., McCloud P.I., Moore A.G., Moore. D.J. Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus. Lancet. 1989;2:709–712. doi: 10.1016/s0140-6736(89)90771-x. [DOI] [PubMed] [Google Scholar]
  16. De Jaeger, G., Buys E., Eeckhout D., De Wilde C., Jacobs A., Kapila J., Angenon G., Van Montagu M., Gerats T., Depicker. A. High level accumulation of single-chain variable fragments in the cytosol of transgenic Petunia hybrida. Eur. J. Biochem. 1999;259:426–434. doi: 10.1046/j.1432-1327.1999.00060.x. [DOI] [PubMed] [Google Scholar]
  17. Devi C.M., Bai M.V., Lal A.V., Umashankar P.R., Krishnan. L.K. An improved method for isolation of antiviper venom antibodies from chicken egg yolk. J. Biochem. Biophys. Methods. 2002;51:129–138. doi: 10.1016/s0165-022x(02)00002-7. [DOI] [PubMed] [Google Scholar]
  18. Dyck M.K., Lacroix D., Pothier F., Sirard. M.A. Making recombinant proteins in animals—different systems, different applications. Trends Biotechnol. 2003;21:394–399. doi: 10.1016/S0167-7799(03)00190-2. [DOI] [PubMed] [Google Scholar]
  19. Ebina T., Sato A., Umezu K., Ishida N., Ohyama S., Ohizumi A., Aikawa K., Katagiri S., Katsushima N., Imai A. Prevention of rotavirus infection by cow colostrum antibody against human rotaviruses. Lancet. 1983;2:1029–1030. doi: 10.1016/s0140-6736(83)91016-4. [DOI] [PubMed] [Google Scholar]
  20. Ebina T., Sato A., Umezu K., Ishida N., Ohyama S., Oizumi A., Aikawa K., Katagiri S., Katsushima N., Imai A. Prevention of rotavirus infection by oral administration of cow colostrum containing anti-humanrotavirus antibody. Med. Microbiol. Immunol. Berl. 1985;174:177–185. doi: 10.1007/BF02123694. [DOI] [PubMed] [Google Scholar]
  21. Ehrlich P. Ueber Immunität durch Verebung und Zeugung. Z. Hyg. Infektionskr. 1892;12:183–203. [Google Scholar]
  22. Filler S.J., Gregory R.L., Michalek S.M., Katz J., McGhee. J.R. Effect of immune bovine milk on Streptococcus mutans in human dental plaque. Arch. Oral Biol. 1991;36:41–47. doi: 10.1016/0003-9969(91)90052-v. [DOI] [PubMed] [Google Scholar]
  23. Fischer R., Schumann D., Zimmermann S., Drossard J., Sack M., Schillberg. S. Expression and characterization of bispecific single-chain Fv fragments produced in transgenic plants. Eur. J. Biochem. 1999;262:810–816. doi: 10.1046/j.1432-1327.1999.00435.x. [DOI] [PubMed] [Google Scholar]
  24. Fischer R., Twyman R.M., Schillberg. S. Production of antibodies in plants and their use for global health. Vaccine. 2003;21:820–825. doi: 10.1016/s0264-410x(02)00607-2. [DOI] [PubMed] [Google Scholar]
  25. Freedman D.J., Tacket C.O., Delehanty A., Maneval D.R., Nataro J., Crabb. J.H. Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli. J. Infect. Dis. 1998;177:662–667. doi: 10.1086/514227. [DOI] [PubMed] [Google Scholar]
  26. Grundbacher F.J. Behring’s discovery of diphtheria and tetanus antitoxins. Immunol. Today. 1992;13:188–190. doi: 10.1016/0167-5699(92)90125-Q. [DOI] [PubMed] [Google Scholar]
  27. Hatta H., Ozeki M., Tsuda. K. In: Egg yolk antibody IgY and its application. Page 151–178 in Hen Eggs: Their Basic and Applied Science. Yamamoto T., Juneja L.R., Hatta H., Kim M., editors. CRC Press; New York: 1997. a. [Google Scholar]
  28. Hatta H., Tsuda K., Ozeki M., Kim M., Yamamoto T., Otake S., Hirasawa M., Katz J., Childers N.K., Michalek. S.M. Passive immunization against dental plaque formation in humans: Effect of a mouth rinse containing egg yolk antibodies IgY specific to Streptococcus mutans. Caries Res. 1997;31:268–274. doi: 10.1159/000262410. b. [DOI] [PubMed] [Google Scholar]
  29. Hayden M.S., Gilliland L.K., Ledbetter. J.A. Antibody engineering. Curr. Opin. Immunol. 1997;9:201–212. doi: 10.1016/s0952-7915(97)80136-7. [DOI] [PubMed] [Google Scholar]
  30. Hennig-Pauka, I., Stelljes I., Waldmann. K.H. Studies on the effect of specific egg antibodies against Escherichia coli infections in piglets. Dtsch. Tierarztl. Wochenschr. 2003;110:49–54. [PubMed] [Google Scholar]
  31. Henrichsen J. Typing of Streptococcus pneumoniae: Past, present, and future. Am. J. Med. 1999;107:50S–54S. doi: 10.1016/s0002-9343(99)00100-x. [DOI] [PubMed] [Google Scholar]
  32. Hiatt A., Cafferkey R., Bowdish. K. Production of antibodies in transgenic plants. Nature. 1989;342:76–78. doi: 10.1038/342076a0. [DOI] [PubMed] [Google Scholar]
  33. Hood E.E., Woodard S.L., Horn. M.E. Monoclonal antibody manufacturing in transgenic plants—Myths and realities. Curr. Opin. Biotechnol. 2002;13:630–635. doi: 10.1016/s0958-1669(02)00351-8. [DOI] [PubMed] [Google Scholar]
  34. Huston J.S., Levinson D., Mudgett-Hunter M., Tai M.S., Novotny J., Margolies M.N., Ridge R.J., Bruccoleri R.E., Haber E., Crea R. Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli. Proc. Natl. Acad. Sci. USA. 1988;85:5879–5883. doi: 10.1073/pnas.85.16.5879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ikemori Y., Kuroki M., Peralta R.C., Yokoyama H., Kodama. Y. Protection of neonatal calves against fatal enteric colibacillosis by administration of egg yolk powder from hens immunized with K99-piliated enterotoxigenic Escherichia coli. Am. J. Vet. Res. 1992;53:2005–2008. [PubMed] [Google Scholar]
  36. Ikemori Y., Ohta M., Umeda K., Icatlo F.C., Jr., Kuroki M., Yokoyama H., Kodama. Y. Passive protection of neonatal calves against bovine coronavirus-induced diarrhea by administration of egg yolk or colostrum antibody powder. Vet. Microbiol. 1997;58:105–111. doi: 10.1016/S0378-1135(97)00144-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Keller M.A., Stiehm. E.R. Passive immunity in prevention and treatment of infectious diseases. Clin. Microbiol. Rev. 2000;13:602–614. doi: 10.1128/cmr.13.4.602-614.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kipriyanov S.M., Le Gall. F. Generation and production of engineered antibodies. Mol. Biotechnol. 2004;26:39–60. doi: 10.1385/MB:26:1:39. [DOI] [PubMed] [Google Scholar]
  39. Korhonen H., Marnila P., Gill. H.S. Bovine milk antibodies for health. Br. J. Nutr. 2000;84(Suppl. 1):S135–S146. doi: 10.1017/s0007114500002361. a. [DOI] [PubMed] [Google Scholar]
  40. Korhonen H., Marnila P., Gill. H.S. Milk immunoglobulins and complement factors. Br. J. Nutr. 2000;84(Suppl. 1):S75–S80. doi: 10.1017/s0007114500002282. b. [DOI] [PubMed] [Google Scholar]
  41. Krause R.M., Dimmock N.J., Morens. D.M. Summary of antibody workshop: The role of humoral immunity in the treatment and prevention of emerging and extant infectious diseases. J. Infect. Dis. 1997;176:549–559. doi: 10.1086/514074. [DOI] [PubMed] [Google Scholar]
  42. Kuby J. Immunoglobulins: Structure and function. Page 111 in Immunology. W. H. Freeman and Company; New York: 1992. [Google Scholar]
  43. Kuroki M., Ohta M., Ikemori Y., Peralta R.C., Yokoyama H., Kodama. Y. Passive protection against bovine rotavirus in calves by specific immunoglobulins from chicken egg yolk. Arch. Virol. 1994;138:143–148. doi: 10.1007/BF01310045. [DOI] [PubMed] [Google Scholar]
  44. Ma J.K., Hiatt A., Hein M., Vine N.D., Wang F., Stabila P., van Dolleweerd C., Mostov K., Lehner. T. Generation and assembly of secretory antibodies in plants. Science. 1995;268:716–719. doi: 10.1126/science.7732380. [DOI] [PubMed] [Google Scholar]
  45. Marquardt R.R., Jin L.Z., Kim J.W., Fang L., Frohlich A.A., Baidoo. S.K. Passive protective effect of egg-yolk antibodies against enterotoxigenic Escherichia coli K88+ infection in neonatal and early-weaned piglets. FEMS Immunol. Med. Microbiol. 1999;23:283–288. doi: 10.1111/j.1574-695X.1999.tb01249.x. [DOI] [PubMed] [Google Scholar]
  46. Maya Devi, C., Vasantha Bai M., Krishnan. L.K. Development of viper-venom antibodies in chicken egg yolk and assay of their antigen binding capacity. Toxicon. 2002;40:857–861. doi: 10.1016/s0041-0101(01)00258-6. [DOI] [PubMed] [Google Scholar]
  47. McCafferty J., Griffiths A.D., Winter G., Chiswell. D.J. Phage antibodies: Filamentous phage displaying antibody variable domains. Nature. 1990;348:552–554. doi: 10.1038/348552a0. [DOI] [PubMed] [Google Scholar]
  48. McFadden T.B., Besser T.E., Barringon. G.M. In: Regulation of immunoglobulin transfer into mammary secretions of ruminants. Pages 133–152 in Milk, Composition, Production and Biotechnology. Welch R.A.S., Burns D.J.W., Davis S.R., Popay A.I., Prosser C.G., editors. CAB International; Wallingford, UK: 1997. [Google Scholar]
  49. Mine Y., Kovacs-Nolan. J. Chicken egg yolk antibodies as therapeutics in enteric infectious disease: A review. J. Med. Food. 2002;5:159–169. doi: 10.1089/10966200260398198. [DOI] [PubMed] [Google Scholar]
  50. Nagesha H.S., Wang L.F., Shiell B., Beddome G., White J.R., Irving. R.A. A single chain Fv antibody displayed on phage surface recognises conformational group-specific epitope of bluetongue virus. J. Virol. Methods. 2001;91:203–207. doi: 10.1016/S0166-0934(00)00266-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Oral H.B., Ozakin C., Akdis. C.A. Back to the future: Antibody-based strategies for the treatment of infectious diseases. Mol. Biotechnol. 2002;21:225–239. doi: 10.1385/MB:21:3:225. [DOI] [PubMed] [Google Scholar]
  52. Owusu-Asiedu, A., Nyachoti C.M., Baidoo S.K., Marquardt R.R., Yang. X. Response of early-weaned pigs to an enterotoxigenic Escherichia coli K88 challenge when fed diets containing spray-dried porcine plasma or pea protein isolate plus egg yolk antibody. J. Anim. Sci. 2003;81:1781–1789. doi: 10.2527/2003.8171781x. [DOI] [PubMed] [Google Scholar]
  53. Pini A., Bracci. L. Phage display of antibody fragments. Curr. Protein Pept. Sci. 2000;1:155–169. doi: 10.2174/1389203003381397. [DOI] [PubMed] [Google Scholar]
  54. Pluckthun A. Antibody engineering. Curr. Opin. Biotechnol. 1991;2:238–246. doi: 10.1016/0958-1669(91)90016-x. [DOI] [PubMed] [Google Scholar]
  55. Reilly R.M., Domingo R., Sandhu. J. Oral delivery of antibodies. Future pharmacokinetic trends. Clin. Pharmacokinet. 1997;32:313–323. doi: 10.2165/00003088-199732040-00004. [DOI] [PubMed] [Google Scholar]
  56. Rose M.E., Orlans E., Buttress. N. Immunoglobulin classes in the hen’s egg: Their segregation in yolk and white. Eur. J. Immunol. 1974;4 doi: 10.1002/eji.1830040715. [DOI] [PubMed] [Google Scholar]
  57. Shimamoto C., Tokioka S., Hirata I., Tani H., Ohishi H., Katsu. K. Inhibition of Helicobacter pylori infection by orally administered yolk-derived anti-Helicobacter pylori antibody. Hepatogastroenterology. 2002;49:709–714. [PubMed] [Google Scholar]
  58. Shin J.H., Yang M., Nam S.W., Kim J.T., Myung N.H., Bang W.G., Roe. I.H. Use of egg yolk-derived immunoglobulin as an alternative to antibiotic treatment for control of Helicobacter pylori infection. Clin. Diagn. Lab. Immunol. 2002;9:1061–1066. doi: 10.1128/CDLI.9.5.1061-1066.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Stoger E., Vaquero C., Torres E., Sack M., Nicholson L., Drossard J., Williams S., Keen D., Perrin Y., Christou P., Fischer. R. Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant. Mol. Biol. 2000;42:583–590. doi: 10.1023/a:1006301519427. [DOI] [PubMed] [Google Scholar]
  60. Tacket C.O., Losonsky G., Link H., Hoang Y., Guesry P., Hilpert H., Levine. M.M. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. N. Engl. J. Med. 1988;318:1240–1243. doi: 10.1056/NEJM198805123181904. [DOI] [PubMed] [Google Scholar]
  61. Thalley B.S., Carroll. S.B. Rattlesnake and scorpion antivenoms from the egg yolks of immunized hens. Biotechnology (N. Y.) 1990;8:934–938. doi: 10.1038/nbt1090-934. [DOI] [PubMed] [Google Scholar]
  62. Torres E., Vaquero C., Nicholson L., Sack M., Stoger E., Drossard J., Christou P., Fischer R., Perrin. Y. Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies. Transgenic Res. 1999;8:441–449. doi: 10.1023/a:1008969031219. [DOI] [PubMed] [Google Scholar]
  63. Van de Perre, P. Transfer of antibody via mother’s milk. Vaccine. 2003;21:3374–3376. doi: 10.1016/s0264-410x(03)00336-0. [DOI] [PubMed] [Google Scholar]
  64. Vaquero C., Sack M., Chandler J., Drossard J., Schuster F., Monecke M., Schillberg S., Fischer. R. Transient expression of a tumor-specific single-chain fragment and a chimeric antibody in tobacco leaves. Proc. Natl. Acad. Sci. USA. 1999;96:11128–11133. doi: 10.1073/pnas.96.20.11128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Warzecha H., Mason. H.S. Benefits and risks of antibody and vaccine production in transgenic plants. J. Plant Physiol. 2003;160:755–764. doi: 10.1078/0176-1617-01125. [DOI] [PubMed] [Google Scholar]
  66. Weisse M.E. The fourth disease, 1900-2000. Lancet. 2001;357:299–301. doi: 10.1016/S0140-6736(00)03623-0. [DOI] [PubMed] [Google Scholar]
  67. Winau F., Winau. R. Emil von Behring and serum therapy. Microbes Infect. 2002;4:185–188. doi: 10.1016/s1286-4579(01)01526-x. [DOI] [PubMed] [Google Scholar]
  68. Winter G., Griffiths A.D., Hawkins R.E., Hoogenboom. H.R. Making antibodies by phage display technology. Annu. Rev. Immunol. 1994;12:433–455. doi: 10.1146/annurev.iy.12.040194.002245. [DOI] [PubMed] [Google Scholar]
  69. Yokoyama H., Peralta R.C., Umeda K., Hashi T., Icatlo F.C., Jr., Kuroki M., Ikemori Y., Kodama. Y. Prevention of fatal salmonellosis in neonatal calves, using orally administered chicken egg yolk Salmonella-specific antibodies. Am. J. Vet. Res. 1998;59:416–420. [PubMed] [Google Scholar]

Articles from Poultry Science are provided here courtesy of Elsevier

RESOURCES