Specific Pathogen Free (SPF) Colonies

Specific Pathogen Free (SPF) macaques are valuable, highly utilized, and well-characterized animal models for biomedical research. In 1989, the National Center for Research Resources (now Office of Research Infrastructure Programs ORIP) of the National Institutes of Health initiated experimental research contracts to establish and maintain SPF colonies. Over the past 25 years SPF colonies have 1) improved animal health and reproduction by elimination of potential animal pathogens, 2) improved the quality of nonhuman primates (NHP) used in biomedical research by providing animals free of potentially confounding intercurrent infections, and 3) reduced potential sources of human occupational exposure to selected NHP viruses (1). These goals have been successfully achieved for the original four selected NHP viruses: Macacine herpesvirus 1, formerly known as Cercopithecine herpesvirus 1 and also known as B virus or Herpes B virus (BV), simian immunodeficiency virus (SIV), simian betaretrovirus formerly known as simian retrovirus type D (SRV), and simian T-cell lymphotropic virus (STLV-1) by employing a test and removal strategy. The strategy relies primarily on two basic requirements; 1) initial and ongoing surveillance testing to correctly identify all infected animals, and 2) a barrier management system to prevent direct and indirect contact between SPF and non-SPF or untested animals (2,3). Today many colonies have successfully employed this strategy to eliminate or characterize infection not only for the original four target viruses, but also for additional pathogens such as simian foamy virus, rhesus cytomegalovirus, rhesus rhadinovirus, simian virus 40, lymphocryptovirus, simian varicella virus, and measles virus (4).

BCMC members contributed to a 2016 review paper (5) outlining current state-of-the-art viral testing programs for deriving and maintaining NHP SPF breeding colonies. This review presents general principles necessary to ensure accurate detection of infection as well as examples for applying these principles to design efficient step-wise algorithms using well-validated, quality-controlled diagnostic tests. In addition, the review discusses the importance of implementing a proficiency assessment program in the context of large multi-institutional SPF macaque breeding programs. The conclusion of this report provides a brief description of how results of viral testing can be applied to the management of SPF macaque breeding colonies.

1.Lerche NW, Yee JL, Jennings MB: Establishing specific retrovirus-free breeding colonies of macaques: an approach to primary screening and surveillance. Lab Anim Sci 1994; 44:217-221.

2.Lerche NW, Osborn KG: Simian retrovirus infections: potential confounding variables in primate toxicology studies. Toxicol Pathol 2003; 31 Suppl:103-110.

3.Morton WR, Agy MB, Capuano SV, Grant RF: Specific pathogen-free macaques: definition, history, and current production. ILAR journal / National Research Council, Institute of Laboratory Animal Resources 2008; 49:137-144.

4.Lerche NW, Simmons JH: Beyond specific pathogen-free: biology and effect of common viruses in macaques. Comp Med 2008; 58:8-10.

5.Yee, J. L., Vandeford, T. H., Didier, E. S., Gray, S., Lewis, A., Roberts, J., … Bohm, R. P. (2016). Specific Pathogen Free Macaque Colonies: A Review of Principles and Recent Advances for Viral Testing and Colony Management. Journal of Medical Primatology, 45(2), 55–78.