AAPS PharmSci

, Volume 4, Issue 4, pp 119–125 | Cite as

Evolving importance of biologics and novel delivery systems in the face of microbial resistance

  • Terry L. BowersockEmail author


Methods to control infectious diseases in livestock are growing in importance. As the size of the average farm increases-for poultry, dairy and beef cattle, swine, and fish-the risk of rapid spread of infectious diseases increases as well. This increases the need for alternative methods of control of infectious agents. Improvements in specific immunogens, adjuvants, and delivery systems are needed to meet the demand for vaccines to ensure a healthy and safe meat supply. This article explores the challenges, trends, and recent advances in the control of infectious diseases through the use of biologics.


biologics vaccines animal health novel delivery systems 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Prescott JF, Dowling PM. Agriculture's role in managing antimicrobial resistance: conference report. Can Vet J. 2000;41:191–197.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Aherne F. Antibiotics-Pro or Con? International Pigletter. 2001;21:55–56.Google Scholar
  3. 3.
    Levy SB. Multidrug resistance-sign of the times. N Engl J Med. 1998;338:1376–1378.CrossRefPubMedGoogle Scholar
  4. 4.
    The Changing Face of the Beef Industry. Cattle Fax. Jan. 2002; Available at: www.cattle-fax.orgGoogle Scholar
  5. 5.
    Ferber D. Drugless chickens make for healthier people. ScienceNow. December 19, 2001. Available at: Scholar
  6. 6.
    National Chicken Council. Antibiotic treatment surges in Denmark as growth promotion ends. December 2001; Available at: Scholar
  7. 7.
    USDA APHIS Veterinary Services. Vaccination of Cattle Against Respiratory Disease Pathogens in U.S. Feedlots. Info Sheet. Washington, DC: Government Printing Office: 2000.Google Scholar
  8. 8.
    Ferber D. Superbugs on the hoof? Science 2000;2889:792–794.CrossRefGoogle Scholar
  9. 9.
    Dho-Moulin M, Fairbrother JM. Avian pathogenic Escherichia coli (APEC). Veter Res. (France). 1999;30:299–316.Google Scholar
  10. 10.
    Chapman PA, Ellin M, Ashton R, Shafique W. Comparison of culture, PCR and immunoassays for detecting Escherichia coli 0157 following enrichment culture and immunomagnetic separation performed on naturally contaminated raw meat products. Int J Food Microbiol. 2001;68:11–20.CrossRefPubMedGoogle Scholar
  11. 11.
    Wang H, Li Y, Slavik MF. Efficacy of cetylpyridinium chloride in immersion treatment for reducing populations of pathogenic bacteria on fresh-cut vegetables. J Food Prot. 2001;64:2071–2074.CrossRefPubMedGoogle Scholar
  12. 12.
    Kramer JM, Frost JA, Bolton FJ, Wareing DR. Campylobacter contamination of raw meat and poultry at retail sale: identification of multiple types and comparison with isolates from human infection. J Food Prot. 2000;63:1654–1659.CrossRefPubMedGoogle Scholar
  13. 13.
    Grave K, Lingaas E, Bangen M, Ronning M. Surveillance of the overall consumption of antibacterial drugs in humans, domestic animals and farmed fish in Norway in 1992 and 1996. J Antimicrob Chemother. 1999;4:243–252.CrossRefGoogle Scholar
  14. 14.
    Bilic V, Lipej Z, Valpotic I, Habrun B, Humski A, Njari B. Mycoplasmal pneumonia in pigs in Croatia: first evaluation of a vaccine in fattening pigs. Acta Veterinaria Hungarica. 1996;44:287–293.PubMedGoogle Scholar
  15. 15.
    Le Grand A, Kobisch M. Comparison of the effects of vaccination and pulse medication in a pig herd infected with Mycoplasma hyopneumoniae. Veter Res. (Paris). 1996;27:241–253.Google Scholar
  16. 16.
    Roof MB, Doitchinoff DD. Safety, efficacy, and duration of immunity induced in swine by use of an avirulent live Salmonella choleraesuiscontaining vaccine. Am J Vet Res. 1995;56:39–44.PubMedGoogle Scholar
  17. 17.
    Methner U, Barrow PA, Berndt A, Steinbach G. Combination of vaccination and competitive exclusion to prevent salmonella colonization in chickens: experimental studies. J Food Microbiol. 1999;49:35–42.CrossRefGoogle Scholar
  18. 18.
    Zhang-Barber L, Turner AK, Barrow PA. Vaccination for control of salmonella in poultry. Vaccine. 1999;17:2538–2545.CrossRefPubMedGoogle Scholar
  19. 19.
    Slauch JM, Mahan MJ, Mekalanos JJ. In vivo expression technology for selection of bacterial genes specifically induced in host tissues. Methods Enzymol. 1994;235:481–492.CrossRefPubMedGoogle Scholar
  20. 20.
    Shea JE, Hensel M, Gleeson C, Holden DW. Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc Natl Acad Sci USA. 1996;93:2593–2597.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Chatfield SN, Strahan K, Pickard D, Charles IG, Hormaeche CE, Dougan G. Evaluation of Salmonella typhimurium strains harbouring defined mutations in htrA and aroA in the murine salmonellosis model. Microb Pathog. 1992;12:145–151.CrossRefPubMedGoogle Scholar
  22. 22.
    Chatfield SN, Roberts M, Dougan G, Hormaeche C, Khan CM. The development of oral vaccines against parasitic diseases utilizing live attenuated Salmonella. Parasitology. 1995;110 Suppl:S17–24CrossRefGoogle Scholar
  23. 23.
    Bowersock TL, Martin S. Vaccine delivery to animals. Adv Drug Deliv Rev. 1999;38:167–194.CrossRefPubMedGoogle Scholar
  24. 24.
    Zhao Z, Leong KW. Controlled delivery of antigens and adjuvants in vaccine development. J Pharm Sci. 1996;85:1261–1270.CrossRefPubMedGoogle Scholar
  25. 25.
    Estuningsih SE, Smooker PM, Wiedosari E, et al. Evaluation ofo antigens of Fascioloa gigantica as vaccines against tropical fasciolosis in cattle. Int J Parasitol. 1997;27:1419–1428.CrossRefPubMedGoogle Scholar
  26. 26.
    Krieg AM, Yi AK, Matson S, et al. CpG motifs in bacterial DNA trigger B-cell activation. Nature 1995;374:546–549.CrossRefPubMedGoogle Scholar
  27. 27.
    Sundquist B, Lovgren K, Morein B. Influenza virus ISCOMS, antibody response in animals. Vaccine. 1988;6:49–53.CrossRefPubMedGoogle Scholar
  28. 28.
    Mumford JA, Jessett DM, Rollinson EA, Hannant, D, Draper ME. Duration of protective efficacy of equine influenza immunostimulating complex/tetanus vaccines. Vet Rec 1994;134:158–162.CrossRefPubMedGoogle Scholar
  29. 29.
    Pizza M, Giuliani MM, Fontana MR, et al. Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants. Vaccine. 2001;19:2534–2541.CrossRefPubMedGoogle Scholar
  30. 30.
    Freytag LC, Clements JD. Bacterial toxins as mucosal adjuvants. Curr Top Microbiol Immunol 1999;2356:215–236.Google Scholar
  31. 31.
    Mrsny RJ, Daugherty AL, McKee ML, Fitzgerald DJ. Bacterial toxins as tools for mucosal vaccination. Drug Discov Today. 2001;7:247–258.CrossRefGoogle Scholar
  32. 32.
    Bowersock TL, Shalaby WSW, Levy M, et al. Evaluation of an orally administered vaccine, sing hydrogels containing bacterial exotoxins of Pasteurella haemolytica, in cattle. Am J Vet Res. 1994;55:502–509.PubMedGoogle Scholar
  33. 33.
    Weng CN, Tzan YL, Liu SD, Lin SY, Lee CJ. Protective effects of an oral microencapsulated Mycoplasma hyopneumoniae vaccine against experimental infection in pigs. Res Vet Sci. 1992;53:42–46.CrossRefPubMedGoogle Scholar
  34. 34.
    Liao CW, Cheng IC, Heh KS, Lin FY, Weng CN. Release characteristics of microspheres prepared by co-spray drying Actinobacillus pleuropneumoniae antigens and aqueous ethylcellulose dispersion. J Microencapsul. 2001;18:285–297.CrossRefPubMedGoogle Scholar
  35. 35.
    Hensel A, Stockhole-Zurwieden N, Petzoldt K, Lubitz W. Oral immunization of pigs with viable or inactivated Actinobacillus pleuropneumoniae serotype 9 induces pulmonary and systemic antibodies against homologous aerosol challenge. Infect Immun. 1995;63:3048–3053.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Lee RW, Strommer J, Hodgins D, Shewen PE, Niu Y, Lo RY. Towards development of an edible vaccine against bovine pneumonic pasteurellosis using transgenic white clover expressing a Mannheimia haemolytica A 1 leukotoxin in 50 fusion protein. Infect Immun. 2001;69:5786–5793.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Hood EE, Witcher DR, Maddock S, et al. Commercial production of avidin from transgenic malze: characterization of transformant, production, processing, extraction and purification. Mol Breed 1998;4:301–312.CrossRefGoogle Scholar
  38. 38.
    Bowersock TL, Martin S. Controlled release vaccines in veterinary medicine. In: Rathbone MJ, Gurny R, eds. Controlled Release Veterinary Drug Delivery: Biological and Pharmaceutical Considerations. Amsterdam, The Netherlands: Elsevier; 2000:269–310CrossRefGoogle Scholar
  39. 39.
    Nally JE, Artiushin S, Sheoran AS, et al. Induction of mucosal and systemic antibody specific for SeMF3 of Streptococcus equi by intranasal vaccination using a sucrose acetate isobutyrate based delivery system. Vaccine. 2000;19:492–497.CrossRefPubMedGoogle Scholar
  40. 40.
    Singh M, Briones M, O'Hagan DT. A novel bioadhesive intranasal delivery system for inactivated influenza vaccines. J Control Release. 2001;70:267–276.CrossRefPubMedGoogle Scholar
  41. 41.
    Opdebeeck JP, Tucker IG. A cholesterol implant used as delivery system to immunize mice with bovine serum albumin. J Control Release. 1993;23:271–279.CrossRefGoogle Scholar
  42. 42.
    Ulmer JB, Donnelly JJ, Parker SE, et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 1993;259:1745–1749.CrossRefPubMedGoogle Scholar
  43. 43.
    Cox GJM, Zamb TJ, Babiuk LA. Bovine herpesvirus 1: immune responses in mice and cattle infected with plasmid DNA. J Virol. 1993;67:5664–5667.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Krishnan BR. Current status of DNA vaccines in veterinary medicine. Adv Drug Deliv Rev. 2000;43:3–11.CrossRefPubMedGoogle Scholar
  45. 45.
    Chen SC, Jones DH, Fynan EF, et al. Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles. J Virol. 1998;72:5757–5761.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Halbur P, Thanawongnuwech R, Brown G, et al. Efficacy of antimicrobial treatments and vaccination regimens for control of porcine reproductive and respiratory syndrome virus and Streptococcus suis coinfection of nursery pigs. J Clin Microbiol. 2000;38:1156–1160.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Greene CE, Schultz RD, Ford RB. Canine vaccination. Vet. Clin North Am Small Anim Pract. 2001;31:473–494.CrossRefPubMedGoogle Scholar
  48. 48.
    Ford RB. Vaccines and vaccinations: the strategic issues. Vet Clin North Am Small Anim Pract. 2001;31:439–453.CrossRefPubMedGoogle Scholar
  49. 49.
    Shao ZJ. Aquaculture pharmaceuticals and biologicals: current perspectives and future possibilities. Adv Drug Deliv Rev. 2001;50:229–243.CrossRefPubMedGoogle Scholar
  50. 50.
    Van Oirschot JT. Present and future of veterinary viral vaccinology: a review. Vet Q. 2001;23:100–108.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2002

Authors and Affiliations

  1. 1.Pharmacia Animal HealthKalamazooUSA

Personalised recommendations