Horizontal transmission of endemic viruses among rhesus macaques (Macaca mulatta): Implications for human cytomegalovirus vaccine/challenge design.

INTRODUCTION: Rhesus macaques are natural hosts to multiple viruses including rhesus cytomegalovirus (RhCMV), rhesus rhadinovirus (RRV), and Simian Foamy Virus (SFV). While viral infections are ubiquitous, viral transmissions to uninfected animals are incompletely defined. Management procedures of macaque colonies include cohorts that are Specific Pathogen Free (SPF). Greater understanding of viral transmission would augment SPF protocols. Moreover, vaccine/challenge studies of human viruses would be enhanced by leveraging transmission of macaque viruses to recapitulate expected challenges of human vaccine trials. MATERIALS AND METHODS: This study characterizes viral transmissions to uninfected animals following inadvertent introduction of RhCMV/RRV/SFV-infected adults to a cohort of uninfected juveniles. Following co-housing with virus-positive adults, juveniles were serially evaluated for viral infection. RESULTS: Horizontal viral transmission was rapid and absolute, reaching 100% penetrance between 19 and 78 weeks. CONCLUSIONS: This study provides insights into viral natural histories with implications for colony management and modeling vaccine-mediated immune protection studies.

Development of a generic real-time PCR assay for simultaneous detection of proviral DNA of simian Betaretrovirus serotypes 1, 2, 3, 4 and 5 and secondary uniplex assays for specific serotype identification.

Simian betaretroviruses (formerly Type D retroviruses; SRV) are a group of closely related retroviruses for which the natural host species are Asian monkeys of the genus Macaca. Five serotypes have been identified by classical neutralization assays and three additional untyped variants have been reported (SRV(Tsukuba), SRV-6, SRV-7). These viruses may be significant pathogens in macaque colonies, causing a broad spectrum of clinical disease secondary to viral-induced immune suppression. Undetected SRV infections in research macaques also represent a potential confounding variable in research protocols and a concern for human caretakers. Intensive testing efforts have been implemented to identify infected animals in established colonies. A real-time quantitative generic multiplex PCR assay was developed that is capable of simultaneous detection of proviral DNA of SRV serotypes 1, 2, 3, 4 and 5. This assay incorporates amplification of the oncostatin M (OSM) gene for confirmation of amplifiable DNA and allows quantitation of the number of proviral copies per cell analyzed in each multiplex reaction. Detection of multiple serotypes by PCR increases the efficiency and cost-effectiveness of SRV screening programs. A panel of SRV serotype-specific uniplex real-time PCR assays for discrimination among the five recognized serotypes is also described.

Comparative efficacy of a canine distemper-measles and a standard measles vaccine for immunization of rhesus macaques (Macaca mulatta).

Measles virus (MV), a highly infective paramyxovirus, has caused sporadic epizootics characterized by high morbidity and increased mortality in nonhuman primates. Measles vaccines for human use, although effective, are cost prohibitive for use in primate colonies. We compared the efficacy of one or two doses of Vanguard D-M, a canine distemper-measles (CD-M) vaccine, with a single dose of Attenuvax, a human measles vaccine. Compared with 81% of animals inoculated with Attenuvax, all animals inoculated with one or two doses of Vanguard developed detectable MV antibodies. One year after immunization, six juveniles from each vaccine group, along with three unvaccinated controls, were challenged with pathogenic MV and were monitored for clinical signs of disease, viremia, viral shedding, and immune response. All uninoculated controls developed clinical disease and viremia, and shed virus in nasopharangeal secretions. Subclinical viremia without viral shedding was identified in two Attenuvax- and two single-dose Vanguard-inoculated animals. Viremia was not detected in any two-dose Vanguard-inoculated animals. Significantly higher neutralization antibody titers were observed in animals receiving Vanguard. Results of this study indicate that Vanguard is at least as efficacious as Attenuvax for protection of rhesus macaques. The considerably lower cost of Vanguard makes vaccination against measles in large breeding colonies economically feasible.