Specific pathogen free macaque colonies: a review of principles and recent advances for viral testing and colony management

Abstract

Specific pathogen free (SPF) macaques provide valuable 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. The derivation and maintenance of SPF macaque colonies is a complex undertaking requiring knowledge of the biology of the agents for exclusion and normal physiology and behavior of macaques, application of the latest diagnostic technology, facilitiy management, and animal husbandry. This review provides information on the biology of the four viral agents targeted for exclusion in ORIP SPF macaque colonies, describes current state-of-the-art viral diagnostic algorithms, presents data from proficiency testing of diagnostic assays between laboratories at institutions participating in the ORIP SPF program, and outlines management strategies for maintaining the integrity of SPF colonies using results of diagnostic testing as a guide to decision making.

Keywords: herpes B virus; macaque colony management; simian T-cell lymphotropic virus; simian betaretrovirus; simian immunodeficiency virus; specific pathogen free; virus testing.

Figure 1

B virus testing algorithm. This example uses rELISA which includes Macacine herpesvirus 1 recombinant antigen or HSV-1 ELISA which includes human Herpes simplex virus 1 antigen. An alternate algorithm successfully uses Herpes virus papio type 2 in either an ELISA or multiplex format. Neg/Pos(2) indicates two consecutive negative or positive tests.

Figure 2

SIV testing algorithm

Figure 3

Example of temporal SRV test results shifts in an infected pig-tailed macaque.

Figure 4

SRV testing algorithm

Figure 5

STLV-1 testing algorithm. a) Testing for antibody (EIA, western blot) is enhanced when using assays containing HTLV recombinant p21e antigen. Early detection of STLV1 infections by EIA is improved by incorporating recombinant HTLV p21e antigen, which demonstrates increased sensitivity over testing that uses HTLV-infected cell lysates without recombinant antigens. b) PCR may be used to augment serology or when serology is not performed frequently or when a single serologic test is being used for selection for inclusion into a SPF colony. Seroconversion may not occur for months to years after infection so PCR testing of seronegative and seroindeterminate samples is warranted in the absence of antibody testing at multiple time points. c) In this example WB or IFA is used as the confirmatory test for non-negative antibody screening tests. To reduce non-specific viral lysate reactivity concerns, some algorithms have preferred and successfully incorporated PCR at this step. (Adapted from: References and 57).