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Antibody production in rabbits administered Freund's complete adjuvant and carprofen concurrently

An Erratum to this article was published on 17 February 2016

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Abstract

Freund's complete adjuvant (FCA) is a commonly used immunopotentiator that can boost polyclonal antibody production in animal models such as rabbits, but FCA is also known to cause inflammation and pain. It is important to balance the welfare of animals with the goal of efficiently producing antibodies, but little is known about how common treatments for pain and inflammation, such as non-steroidal anti-inflammatory drugs (NSAIDs), affect the production of polyclonal antibodies. The purpose of this study was to measure polyclonal antibody production in rabbits that were administered FCA either with or without a concurrent treatment of a NSAID, carprofen. Rabbits were divided into two groups and were administered identical treatments of an antigen with adjuvant, and the treatment group also received carprofen injections at different stages of the study. Carprofen treatment did not significantly affect polyclonal antibody production, which suggests that carprofen and other NSAIDs can be used alongside FCA in rabbits to achieve desired levels of antibody production while minimizing pain and distress associated with the use of FCA.

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Figure 1: Timeline of treatments and sampling for rabbits that received no analgesia (control) or carprofen (NSAID) during the experiment.
Figure 2: Mean ± standard error of the mean (s.e.m.) binding antibody titers of rabbits during polyclonal antibody production with and without concurrent treatment with carprofen, as estimated using indirect ELISA.

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  • 27 January 2016

    In the version of this article published in print, the affiliation for the five authors was omitted. The error was corrected in the HTML and PDF versions of the article before online publication.

References

  1. Legge, T.M. & Oxon, M.D. The Milroy lectures on industrial anthrax: delivered before the Royal College of Physicians of London. BMJ 1, 589–593 (1905).

    Article  CAS  Google Scholar 

  2. Leenaars, P.P., Hendriksen, C.F.M., Angulo, A.F., Koedam, M.A. & Claassen, E. Evaluation of several adjuvants as alternatives to the use of Freund's adjuvant in rabbits. Vet. Immunol. Immunopathol. 40, 225–241 (1994).

    Article  CAS  Google Scholar 

  3. Lipman, N.S., Trudel, L.J., Murphy, J.C. & Sahali, Y. Comparison of immune response potentiation and in vivo inflammatory effects of Freund's and RIBI adjuvants in mice. Lab. Anim. Sci. 42, 193–197 (1992).

    CAS  Google Scholar 

  4. Johnston, B.A., Eisen, H. & Fry, D. An evaluation of several adjuvant emulsion regimens for the production of polyclonal antisera in rabbits. Lab. Anim. Sci. 41, 15–21 (1991).

    CAS  Google Scholar 

  5. Mallon, F.M., Graichen, M.E., Conway, B.R., Landi, M.S. & Hughes, H.C. Comparison of antibody response by use of synthetic adjuvant system and Freund complete adjuvant in rabbits. Am. J. Vet. Res. 52, 1503–1506 (1991).

    CAS  Google Scholar 

  6. Smith, D.E., O'Brien, M.E., Palmer, V.J. & Sadowski, J.A. The selection of an adjuvant emulsion for polyclonal antibody production using a low-molecular-weight antigen in rabbits. Lab. Anim. Sci. 42, 599–601 (1992).

    CAS  Google Scholar 

  7. Stills, H.F. Adjuvants and antibody production: dispelling the myths associated with Freund's complete and other adjuvants. ILAR J. 46, 280–293 (2005).

    Article  CAS  Google Scholar 

  8. Stills, H.F. & Bailey, M.Q. The use of Freund's complete adjuvant. Lab. Anim. Sci. 20, 25–31 (1991).

    Google Scholar 

  9. Broderson, J.R. A retrospective review of lesions associated with the use of Freund's adjuvant. Lab. Anim. Sci. 39, 400–405 (1989).

    CAS  Google Scholar 

  10. Jackson, L.R. & Fox, J.G. Institutional policies and guidelines on adjuvants and antibody production. ILAR J. 37, 141–152 (1995).

    Article  Google Scholar 

  11. Amyx, H.L. Control of animal pain and distress in antibody production and infectious disease studies. J. Am. Vet. Med. Assoc. 191, 1287–1289 (1987).

    CAS  PubMed  Google Scholar 

  12. US Department of Agriculture. Animal Care Policy Manual. (USDA, Riverdale, MD, 2015).

  13. Animal Welfare Regulations. 2008. Code of Federal Regulations. Title 9, Part 2, Subpart C.

  14. Animal Welfare Act as Amended. 2008. United States Code. Title 7, Chapter 54, Section 2143.

  15. National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals. Recognition and Alleviation of Pain in Laboratory Animals (National Academies Press, Washington, DC, 2009).

  16. Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals 8th edn. (National Academies Press, Washington, DC, 2011).

  17. American College of Laboratory Animal Medicine. Guidelines for the Assessment and Management of Pain in Rodents and Rabbits (American College of Laboratory Animal Medicine, 2006). http://www.aclam.org/Content/files/files/Public/Active/position_pain-rodent-rabbit.pdf.

  18. Kolstad, A.M., Rodriguiz, R.M., Kim, C.J. & Hale, L.P. Effect of pain management on immunization efficacy in mice. J. Am. Assoc. Lab. Anim. Sci. 51, 448–457 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Halliday, L.C., Artwohl, J.E., Hanly, W.C., Bunte, R.M. & Bennett, B.T. Physiologic and behavioral assessment of rabbits immunized with Freund's complete adjuvant. Contemp. Top. Lab. Anim. Sci. 39, 8–13 (2000).

    CAS  PubMed  Google Scholar 

  20. Halliday, L.C., Artwohl, J.E., Bunte, R.M., Ramakrishnan, V. & Bennett, B.T. Effects of Freund's complete adjuvant on the physiology, histology, and activity of New Zealand White Rabbits. Contemp. Top. Lab. Anim. Sci. 43, 8–13 (2004).

    CAS  PubMed  Google Scholar 

  21. Ben-Baruch, A. Inflammation-associated immune suppression in cancer: The roles played by cytokines, chemokines and additional mediators. Semin. Cancer Biol. 16, 38–52 (2006).

    Article  CAS  Google Scholar 

  22. Cho, J.Y. Immunomodulatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) at the clinically available doses. Arch. Pharm. Res. 30, 64–74 (2007).

    Article  CAS  Google Scholar 

  23. Hussain, M., Javeed, A., Ashraf, M., Al-Zaubai, N., Stewart, A. & Mahmood-Mukhtar, M. Non-steroidal anti-inflammatory drugs, tumour immunity and immunotherapy. Pharmacol. Res. 66, 7–18 (2012).

    Article  CAS  Google Scholar 

  24. Vane, J.R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat. New Biol. 231, 232–235 (1971).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Ms. Sabrina Stronsky, Dr. Pamela Glass, MAJ Amy Carlson and Mr. William Discher for their assistance and support of this project. The opinions, interpretations, conclusions and recommendations are those of the authors and not necessarily endorsed by the US Army.

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Correspondence to Joanna E. Fishback.

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Fishback, J., Stronsky, S., Green, C. et al. Antibody production in rabbits administered Freund's complete adjuvant and carprofen concurrently. Lab Anim 45, 63–66 (2016). https://doi.org/10.1038/laban.937

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