The Importance of Animal Models in the Development of Vaccines

  • Tadele G. Kiros
  • Benoît Levast
  • Gaël Auray
  • Stacy Strom
  • Jill van Kessel
  • Volker GerdtsEmail author


Efficient translation of basic vaccine research into clinical therapies greatly depends upon the availability of appropriate animal models. Testing novel vaccine candidates in animal models is a critical step in the development of modern vaccines. Animal models are being used to assess the quality and quantity of the immune response, to identify the optimal route of delivery and formulation, to determine protection from infection and disease transmission, and to evaluate the safety and toxicity of the vaccine formulation. Animal models help to make the translation from basic research to clinical application, and they often allow prediction of the vaccine potential, which helps in predicting the financial risks for vaccine manufacturers. Choosing an appropriate animal model has become increasingly important for the field, as each model has its own advantages and disadvantages. In this review, the criteria for selecting the right animal model, the advantages and disadvantages of various animal models, as well as the future needs for animal models are being discussed.


Animal model Vaccine development Vaccine delivery Infectious disease 


  1. Aich P, Wilson HL, Kaushik RS, Potter AA, Babiuk LA, Griebel P (2007) Comparative analysis of innate immune responses following infection of newborn calves with bovine rotavirus and bovine coronavirus. J Gen Virol 88:2749–2761PubMedCrossRefGoogle Scholar
  2. Baron C, Coombes B (2007) Targeting bacterial secretion systems: benefits of disarmament in the microcosm. Infect Disord Drug Targets 7:19–27PubMedCrossRefGoogle Scholar
  3. Bishop SC, Lunney JK, Pinard-van der Laan MH MH, Gay CG (2011) Report from the second international symposium on animal genomics for animal health: critical needs, challenges and potential solutions. BMC Proc 5(Suppl 4):S1PubMedCrossRefGoogle Scholar
  4. Blanchard-Rohner G, Siegrist CA (2011) Vaccination during pregnancy to protect infants against influenza: why and why not? Vaccine 29:7542–7550PubMedCrossRefGoogle Scholar
  5. Dobrescu L, Huygelen C (1976) Protection of piglets against neonatal E. coli enteritis by immunization of the sow with a vaccine containing heat-labile enterotoxin (LT) I. Protection against experimentally induced diarrhoea. Zentralb Veterinarmed B 23:79–88CrossRefGoogle Scholar
  6. Edwards KM (2003) Pertussis: an important target for maternal immunization. Vaccine 21:3483–3486PubMedCrossRefGoogle Scholar
  7. Elahi S, Brownlie R, Korzeniowski J, Buchanan R, O’Connor B, Peppler MS, Halperin SA, Lee SF, Babiuk LA, Gerdts V (2005) Infection of newborn piglets with Bordetella pertussis: a new model for pertussis. Infect Immun 73:3636–3645PubMedCrossRefGoogle Scholar
  8. Elahi S, Holmstrom J, Gerdts V (2007) The benefits of using diverse animal models for studying pertussis. Trends Microbiol 15:462–468PubMedCrossRefGoogle Scholar
  9. Gerdts V, Babiuk LA, van Drunen Littel-van den H, Griebel PJ (2000) Fetal immunization by a DNA vaccine delivered into the oral cavity. Nat Med 6:929–932PubMedCrossRefGoogle Scholar
  10. Gerdts V, Uwiera RR, Mutwiri GK, Wilson DJ, Bowersock T, Kidane A, Babiuk LA, Griebel PJ (2001) Multiple intestinal ‘loops’ provide an in vivo model to analyse multiple mucosal immune responses. J Immunol Methods 256:19–33PubMedCrossRefGoogle Scholar
  11. Gerdts V, Snider M, Brownlie R, Babiuk LA, Griebel PJ (2002) Oral DNA vaccination in utero induces mucosal immunity and immune memory in the neonate. J Immunol 168:1877–1885PubMedGoogle Scholar
  12. Gerdts V, Mutwiri GK, Tikoo SK, Babiuk LA (2006) Mucosal delivery of vaccines in domestic animals. Vet Res 37:487–510PubMedCrossRefGoogle Scholar
  13. Gerdts V, Littel-van den Hurk SD, Griebel PJ, Babiuk LA (2007) Use of animal models in the development of human vaccines. Future Microbiol 2:667–675PubMedCrossRefGoogle Scholar
  14. Girard-Misguich F, Cognie J, Delgado-Ortega M, Berthon P, Rossignol C, Larcher T, Melo S, Bruel T, Guibon R, Cherel Y, Sarradin P, Salmon H, Guillen N, Meurens F (2011) Towards the establishment of a porcine model to study human amebiasis. PLoS One 6:e28795PubMedCrossRefGoogle Scholar
  15. Gracia A, Polewicz M, Halperin SA, Hancock RE, Potter AA, Babiuk LA, Gerdts V (2011) Antibody responses in adult and neonatal Balb/c mice to immunization with novel Bordetella pertussis vaccine formulations. Vaccine 29:1595–1604PubMedCrossRefGoogle Scholar
  16. Hall RA, Khromykh AA (2004) West Nile virus vaccines. Expert Opin Biol Ther 4:1295–1305PubMedCrossRefGoogle Scholar
  17. Hein WR, Griebel PJ (2003) A road less travelled: large animal models in immunological research. Nat Rev Immunol 3:79–84PubMedCrossRefGoogle Scholar
  18. Jalal S, Arsenault R, Potter AA, Babiuk LA, Griebel PJ, Napper S (2009) Genome to kinome: species-specific peptide arrays for kinome analysis. Sci Signal 2:pl1PubMedCrossRefGoogle Scholar
  19. Kohara J, Hirai T, Mori K, Ishizaki H, Tsunemitsu H (1997) Enhancement of passive immunity with maternal vaccine against newborn calf diarrhea. J Vet Med Sci 59:1023–1025PubMedCrossRefGoogle Scholar
  20. Kovacs-Nolan J, Latimer L, Landi A, Jenssen H, Hancock RE, Babiuk LA, van Drunen Littel-van den Hurk S (2009) The novel adjuvant combination of CpG ODN, indolicidin and polyphosphazene induces potent antibody- and cell-mediated immune responses in mice. Vaccine 27:2055–2064PubMedCrossRefGoogle Scholar
  21. Lambert PH, Liu M, Siegrist CA (2005) Can successful vaccines teach us how to induce efficient protective immune responses? Nat Med 11:S54–S62PubMedCrossRefGoogle Scholar
  22. Lang PO, Govind S, Mitchell WA, Siegrist CA, Aspinall R (2011) Vaccine effectiveness in older individuals: what has been learned from the influenza-vaccine experience. Ageing Res Rev 10:389–395PubMedCrossRefGoogle Scholar
  23. Macchiarini F, Manz MG, Palucka AK, Shultz LD (2005) Humanized mice: are we there yet? J Exp Med 202:1307–1311PubMedCrossRefGoogle Scholar
  24. McNulty MS, Logan EF (1987) Effect of vaccination of the dam on rotavirus infection in young calves. Vet Rec 120:250–252PubMedCrossRefGoogle Scholar
  25. Meurens F, Berri M, Auray G, Melo S, Levast B, Virlogeux-Payant I, Chevaleyre C, Gerdts V, Salmon H (2009) Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops. Vet Res 40:5PubMedCrossRefGoogle Scholar
  26. Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V (2012) The pig: a model for human infectious diseases. Trends Microbiol 20:50–57PubMedCrossRefGoogle Scholar
  27. Mostl K, Burki F (1988) Incidence of diarrhoea and of rotavirus- and coronavirus-shedding in calves, whose dams had been vaccinated with an experimental oil-adjuvanted vaccine containing bovine rotavirus and bovine coronavirus. Zentralb Veterinarmed B 35:186–196Google Scholar
  28. Moxon ER, Siegrist CA (2011) The next decade of vaccines: societal and scientific challenges. Lancet 378:348–359PubMedCrossRefGoogle Scholar
  29. Mutwiri G, Bowersock T, Kidane A, Sanchez M, Gerdts V, Babiuk LA, Griebel P (2002) Induction of mucosal immune responses following enteric immunization with antigen delivered in alginate microspheres. Vet Immunol Immunopathol 87:269–276PubMedCrossRefGoogle Scholar
  30. Mutwiri G, Bowersock TL, Babiuk LA (2005) Microparticles for oral delivery of vaccines. Expert Opin Drug Deliv 2:791–806PubMedCrossRefGoogle Scholar
  31. Mutwiri G, Gerdts V, van Drunen Littel-van den Hurk S, Auray G, Eng N, Garlapati S, Babiuk LA, Potter A (2011) Combination adjuvants: the next generation of adjuvants? Expert Rev Vaccines 10:95–107PubMedCrossRefGoogle Scholar
  32. Osterrieder N, Kamil JP, Schumacher D, Tischer BK, Trapp S (2006) Marek’s disease virus: from miasma to model. Nat Rev Microbiol 4:283–294PubMedCrossRefGoogle Scholar
  33. Poehling KA, Szilagyi PG, Staat MA, Snively BM, Payne DC, Bridges CB, Chu SY, Light LS, Prill MM, Finelli L, Griffin MR, Edwards KM (2011) Impact of maternal immunization on influenza hospitalizations in infants. Am J Obstet Gynecol 204:S141–S148PubMedCrossRefGoogle Scholar
  34. Polewicz M, Gracia A, Buchanan R, Strom S, Halperin SA, Potter AA, Babiuk LA, Gerdts V (2011) Influence of maternal antibodies on active pertussis toxoid immunization of neonatal mice and piglets. Vaccine 29:7718–7726PubMedCrossRefGoogle Scholar
  35. Potter AA, Klashinsky S, Li Y, Frey E, Townsend H, Rogan D, Erickson G, Hinkley S, Klopfenstein T, Moxley RA, Smith DR, Finlay BB (2004) Decreased shedding of Escherichia coli O157:H7 by cattle following vaccination with type III secreted proteins. Vaccine 22:362–369PubMedCrossRefGoogle Scholar
  36. PrabhuDas M, Adkins B, Gans H, King C, Levy O, Ramilo O, Siegrist CA (2011) Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol 12:189–194PubMedCrossRefGoogle Scholar
  37. Prysliak T, van der Merwe J, Lawman Z, Wilson D, Townsend H, van Drunen Littel-van den Hurk S, Perez-Casal J (2011) Respiratory disease caused by Mycoplasma bovis is enhanced by exposure to bovine herpes virus 1 (BHV-1) and not to bovine viral diarrhea virus (BVDV) type 2. Can Vet J 52:1195–1202PubMedGoogle Scholar
  38. Rodriguez-Inigo E, Bartolome J, Ortiz-Movilla N, Platero C, Lopez-Alcorocho JM, Pardo M, Castillo I, Carreno V (2005) Hepatitis C virus (HCV) and hepatitis B virus (HBV) can coinfect the same hepatocyte in the liver of patients with chronic HCV and occult HBV infection. J Virol 79:15578–15581PubMedCrossRefGoogle Scholar
  39. Rothel JS, Corner LA, Lightowlers MW, Seow HF, McWaters P, Entrican G, Wood PR (1998) Antibody and cytokine responses in efferent lymph following vaccination with different adjuvants. Vet Immunol Immunopathol 63:167–183PubMedCrossRefGoogle Scholar
  40. Rouse BT, Kaistha SD (2006) A tale of 2 alpha-herpesviruses: lessons for vaccinologists. Clin Infect Dis 42:810–817PubMedCrossRefGoogle Scholar
  41. Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130PubMedCrossRefGoogle Scholar
  42. Storz J, Lin X, Purdy CW, Chouljenko VN, Kousoulas KG, Enright FM, Gilmore WC, Briggs RE, Loan RW (2000) Coronavirus and Pasteurella infections in bovine shipping fever pneumonia and Evans’ criteria for causation. J Clin Microbiol 38:3291–3298PubMedGoogle Scholar
  43. van Drunen Littel-van den Hurk S, Hannaman D (2010) Electroporation for DNA immunization: clinical application. Expert Rev Vaccines 9:503–517PubMedCrossRefGoogle Scholar
  44. van Drunen Littel-van den Hurk S, Babiuk S, Babiuk LA (2006) Needle-free delivery of veterinary DNA vaccines. Methods Mol Med 127:91–105PubMedGoogle Scholar
  45. van Drunen Littel-van den Hurk S, Luxembourg A, Ellefsen B, Wilson D, Ubach A, Hannaman D, van den Hurk JV (2008) Electroporation-based DNA transfer enhances gene expression and immune responses to DNA vaccines in cattle. Vaccine 26:5503–5509PubMedCrossRefGoogle Scholar
  46. van Drunen Littel-van den Hurk S, Lawman Z, Wilson D, Luxembourg A, Ellefsen B, van den Hurk JV, Hannaman D (2010) Electroporation enhances immune responses and protection induced by a bovine viral diarrhea virus DNA vaccine in newborn calves with maternal antibodies. Vaccine 28:6445–6454PubMedCrossRefGoogle Scholar
  47. Wiles S, Hanage WP, Frankel G, Robertson B (2006) Modelling infectious disease - time to think outside the box? Nat Rev Microbiol 4:307–312PubMedCrossRefGoogle Scholar
  48. Wilkie B, Mallard B (1999) Selection for high immune response: an alternative approach to animal health maintenance? Vet Immunol Immunopathol 72:231–235PubMedCrossRefGoogle Scholar
  49. Xu M, Wang S, Li L, Lei L, Liu Y, Shi W, Wu J, Rong F, Sun G, Xiang H, Cai X (2010) Secondary infection with Streptococcus suis serotype 7 increases the virulence of highly pathogenic porcine reproductive and respiratory syndrome virus in pigs. Virol J 7:184PubMedCrossRefGoogle Scholar
  50. Yardley JH, Keren DF, Hamilton SR, Brown GD (1978) Local (immunoglobulin A) immune response by the intestine to cholera toxin and its partial suppression with combined systemic and intra-intestinal immunization. Infect Immun 19:589–597PubMedGoogle Scholar
  51. Yates WD (1982) A review of infectious bovine rhinotracheitis, shipping fever pneumonia and viral-bacterial synergism in respiratory disease of cattle. Can J Comp Med 46:225–263PubMedGoogle Scholar
  52. Yen HH, Scheerlinck JP, Gekas S, Sutton P (2006) A sheep cannulation model for evaluation of nasal vaccine delivery. Methods 38:117–123PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Tadele G. Kiros
    • 1
  • Benoît Levast
    • 1
  • Gaël Auray
    • 1
  • Stacy Strom
    • 1
  • Jill van Kessel
    • 1
  • Volker Gerdts
    • 1
    Email author
  1. 1.Vaccine and Infectious Disease Organization-InterVac, and Department of Veterinary MicrobiologyUniversity of SaskatchewanSaskatoonCanada

Personalised recommendations