The Final (Oral Ebola) Vaccine Trial on Captive Chimpanzees?

Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested that, although sedation induced acute stress, experimental housing conditions did not induce traumatic levels of chronic stress. Acute behavioral and physiological responses to sedation were strongly correlated with immune responses to vaccination. These results suggest that oral vaccination holds great promise as a tool for the conservation of apes and other endangered tropical wildlife. They also imply that vaccine and drug trials on other captive species need to better account for the effects of stress on immune response

Semen evaluation for verification of azoospermia after vasectomy in chimpanzees (Pan troglodytes)

Standards for the reproductive management of captive chimpanzees stipulate that chimpanzees admitted into the National Chimpanzee Sanctuary System must undergo vasectomy followed by laboratory confirmation of azoospermia. In light of the observations of ourselves and others, we questioned whether azoospermia is a necessary indicator of successful vasectomy. Therefore, the objectives of the present study were to assess how much time is required between vasectomy and semen evaluation for azoospermia to be reached and to determine the percentage of vasectomized chimpanzees that actually are azoospermic. The study population comprised 39 adult male chimpanzees that underwent vasectomy and subsequent semen examination at 0.5 to 24 mo afterward. Overall, spermatozoa were found in the semen of at least 1 chimpanzee in almost every month in which animals were evaluated. Of the animals evaluated repeatedly after vasectomy, 20% had no sperm at any examination, 60% were azoospermic then positive during at least 1 subsequent examination, 13.3% were positive at least once and then azoospermic, and 6.7% were positive at every examination. After 0.5 mo postvasectomy, all sperm observed were nonmotile. The results suggest that azoospermia is not a necessary indicator of successful vasectomy

Tuberculosis detection in nonhuman primates is enhanced by use of testing algorithms that include an interferon-γ release assay.

ObjectiveTo develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates.AnimalsCohorts of captive-bred and wild-caught macaques from 5 different geographic regions.ProceduresMacaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks.ResultsSensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks.Clinical relevanceThe detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay

Variable Patterns of Programmed Death-1 Expression on Fully Functional Memory T Cells after Spontaneous Resolution of Hepatitis C Virus Infection▿

The inhibitory receptor programmed death-1 (PD-1) is present on CD8+ T cells in chronic hepatitis C virus (HCV), but expression patterns in spontaneously resolving infections are incompletely characterized. Here we report that PD-1 was usually absent on memory CD8+ T cells from chimpanzees with resolved infections, but sustained low-level expression was sometimes observed in the absence of apparent virus replication. PD-1-positive memory T cells expanded and displayed antiviral activity upon reinfection with HCV, indicating conserved function. This animal model should facilitate studies of whether PD-1 differentially influences effector and memory T-cell function in resolved versus persistent human infections

Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection.

The inhibitory receptor programmed death-1 (PD-1) is present on CD8(+) T cells in chronic hepatitis C virus (HCV), but expression patterns in spontaneously resolving infections are incompletely characterized. Here we report that PD-1 was usually absent on memory CD8(+) T cells from chimpanzees with resolved infections, but sustained low-level expression was sometimes observed in the absence of apparent virus replication. PD-1-positive memory T cells expanded and displayed antiviral activity upon reinfection with HCV, indicating conserved function. This animal model should facilitate studies of whether PD-1 differentially influences effector and memory T-cell function in resolved versus persistent human infections