Single-Shot ChAd3-MARV Vaccine in Modified Formulation Buffer Shows 100% Protection of NHPs.

Marburg virus (MARV) is a virus of high human consequence with a case fatality rate of 24-88%. The global health and national security risks posed by Marburg virus disease (MVD) underscore the compelling need for a prophylactic vaccine, but no candidate has yet reached regulatory approval. Here, we evaluate a replication-defective chimpanzee adenovirus type 3 (ChAd3)-vectored MARV Angola glycoprotein (GP)-expressing vaccine against lethal MARV challenge in macaques. The ChAd3 platform has previously been reported to protect against the MARV-related viruses, Ebola virus (EBOV) and Sudan virus (SUDV), and MARV itself in macaques, with immunogenicity demonstrated in macaques and humans. In this study, we present data showing 100% protection against MARV Angola challenge (versus 0% control survival) and associated production of GP-specific IgGs generated by the ChAd3-MARV vaccine following a single dose of 1 × 1011 virus particles prepared in a new clinical formulation buffer designed to enhance product stability. These results are consistent with previously described data using the same vaccine in a different formulation and laboratory, demonstrating the reproducible and robust protective efficacy elicited by this promising vaccine for the prevention of MVD. Additionally, a qualified anti-GP MARV IgG ELISA was developed as a critical pre-requisite for clinical advancement and regulatory approval.

Development of a Well-Characterized Cynomolgus Macaque Model of Sudan Virus Disease for Support of Product Development.

The primary objective of this study was to characterize the disease course in cynomolgus macaques exposed to Sudan virus (SUDV), to determine if infection in this species is an appropriate model for the evaluation of filovirus countermeasures under the FDA Animal Rule. Sudan virus causes Sudan virus disease (SVD), with an average case fatality rate of approximately 50%, and while research is ongoing, presently there are no approved SUDV vaccines or therapies. Well characterized animal models are crucial for further developing and evaluating countermeasures for SUDV. Twenty (20) cynomolgus macaques were exposed intramuscularly to either SUDV or sterile phosphate-buffered saline; 10 SUDV-exposed animals were euthanized on schedule to characterize pathology at defined durations post-exposure and 8 SUDV-exposed animals were not part of the scheduled euthanasia cohort. Survival was assessed, along with clinical observations, body weights, body temperatures, hematology, clinical chemistry, coagulation, viral load (serum and tissues), macroscopic observations, and histopathology. There were statistically significant differences between SUDV-exposed animals and mock-exposed animals for 26 parameters, including telemetry body temperature, clinical chemistry parameters, hematology parameters, activated partial thromboplastin time, serum viremia, and biomarkers that characterize the disease course of SUDV in cynomolgus macaques.

Development of a Well-Characterized Cynomolgus Macaque Model of Marburg Virus Disease for Support of Vaccine and Therapy Development.

Marburg virus (MARV) is a filovirus that can infect humans and nonhuman primates (NHPs), causing severe disease and death. Of the filoviruses, Ebola virus (EBOV) has been the primary target for vaccine and therapeutic development. However, MARV has an average case fatality rate of approximately 50%, the infectious dose is low, and there are currently no approved vaccines or therapies targeted at infection with MARV. The purpose of this study was to characterize disease course in cynomolgus macaques intramuscularly exposed to MARV Angola variant. There were several biomarkers that reliably correlated with MARV-induced disease, including: viral load; elevated total clinical scores; temperature changes; elevated ALT, ALP, BA, TBIL, CRP and decreased ALB values; decreased lymphocytes and platelets; and prolonged PTT. A scheduled euthanasia component also provided the opportunity to study the earliest stages of the disease. This study provides evidence for the application of this model to evaluate potential vaccines and therapies against MARV and will be valuable in improving existing models.

Transboundary Animal Diseases, an Overview of 17 Diseases with Potential for Global Spread and Serious Consequences.

Animals provide food and other critical resources to most of the global population. As such, diseases of animals can cause dire consequences, especially disease with high rates of morbidity or mortality. Transboundary animal diseases (TADs) are highly contagious or transmissible, epidemic diseases, with the potential to spread rapidly across the globe and the potential to cause substantial socioeconomic and public health consequences. Transboundary animal diseases can threaten the global food supply, reduce the availability of non-food animal products, or cause the loss of human productivity or life. Further, TADs result in socioeconomic consequences from costs of control or preventative measures, and from trade restrictions. A greater understanding of the transmission, spread, and pathogenesis of these diseases is required. Further work is also needed to improve the efficacy and cost of both diagnostics and vaccines. This review aims to give a broad overview of 17 TADs, providing researchers and veterinarians with a current, succinct resource of salient details regarding these significant diseases. For each disease, we provide a synopsis of the disease and its status, species and geographic areas affected, a summary of in vitro or in vivo research models, and when available, information regarding prevention or treatment.

Comparison of oral, nebulized and combination antibiotic treatment of Bordetella bronchiseptica in baboons (Papio spp.).

Incidence of Bordetella pertussis, the causative agent of whooping cough, is rising in some global human populations despite high vaccination rates, and significant research is underway to address the issue. Baboons are an established model for pertussis research, but like many mammals, they can be naturally infected with Bordetella bronchiseptica. Because B. bronchiseptica interferes with B. pertussis research, it must be excluded from baboons under consideration for enrollment in pertussis studies. In addition to research-related concerns, B. bronchiseptica can sometimes cause clinical disease in baboons and other nonhuman primates. This study examined the use of antibiotics to clear B. bronchiseptica in naturally infected baboons. Thirty-five juvenile baboons were divided into five treatment groups: oral sulfamethoxazole/trimethoprim (TMS), nebulized gentamicin (gentamicin), combination (TMS + gentamicin) in positive animals, combination (TMS + gentamicin) as a prophylactic in exposed animals and no treatment (control). Combination of oral TMS and nebulized gentamicin given to positive animals was most effective, producing long-term clearance in 11 out of 12 treated animals. To avoid unnecessary use of antibiotics, our primary management strategy is screening and separating to allow natural clearance and limiting exposure to non-infected animals, but this study investigates an antibiotic regimen that could be used in special circumstances.

Myeloproliferative Disorder with Intraoral Lesions in an Olive Baboon (Papio anubis).

Spontaneous myeloid leukemia is rarely reported in non-human primates. We report a case of myeloproliferative disorder suggestive of acute myeloid leukemia with intraoral lesions in an olive baboon (Papio anubis). Clinical pathology, radiology, gross examination (pre-mortem and post-mortem), histopathology, and immunohistochemistry findings are provided.

Compassion Fatigue, Euthanasia Stress, and Their Management in Laboratory Animal Research.

This review is designed to assist both individuals and organizations involved in animal-based research to understand and appreciate the importance and potential risks of compassion fatigue and euthanasia stress. We reviewed current literature regarding compassion fatigue and euthanasia stress as they relate to the laboratory animal science community. Definitions, recognition, and mitigation steps are clarified. We offer educational and mitigation advice and present needs for future research on these topics that is related directly to the laboratory animal science community.

Booklice (Liposcelis spp.), Grain Mites (Acarus siro), and Flour Beetles (Tribolium spp.): 'Other Pests' Occasionally Found in Laboratory Animal Facilities.

Pests that infest stored food products are an important problem worldwide. In addition to causing loss and consumer rejection of products, these pests can elicit allergic reactions and perhaps spread disease-causing microorganisms. Booklice (Liposcelis spp.), grain mites (Acarus siro), and flour beetles (Tribolium spp.) are common stored-product pests that have previously been identified in our laboratory animal facility. These pests traditionally are described as harmless to our animals, but their presence can be cause for concern in some cases. Here we discuss the biology of these species and their potential effects on human and animal health. Occupational health risks are covered, and common monitoring and control methods are summarized.

Accuracy of Human and Veterinary Point-of-Care Glucometers for Use in Rhesus Macaques (Macaca mulatta), Sooty Mangabeys (Cercocebus atys), and Chimpanzees (Pan troglodytes).

Handheld, point-of-care glucometers are commonly used in NHP for clinical and research purposes, but whether these devices are appropriate for use in NHP is unknown. Other animal studies indicate that glucometers should be species-specific, given differences in glucose distribution between RBC and plasma; in addition, Hct and sampling site (venous compared with capillary) influence glucometer readings. Therefore, we compared the accuracy of 2 human and 2 veterinary glucometers at various Hct ranges in rhesus macaques (Macaca mulatta), sooty mangabeys (Cercocebus atys), and chimpanzees (Pan troglodytes) with that of standard laboratory glucose analysis. Subsequent analyses assessed the effect of hypoglycemia, hyperglycemia, and sampling site on glucometer accuracy. The veterinary glucometers overestimated blood glucose (BG) values in all species by 26 to 75 mg/dL. The mean difference between the human glucometers and the laboratory analyzer was 7 mg/dL or less in all species. The human glucometers overestimated BG in hypoglycemic mangabeys by 4 mg/dL and underestimated BG in hyperglycemic mangabeys by 11 mg/dL; similar patterns occurred in rhesus macaques. Hct did not affect glucometer accuracy, but all samples were within the range at which glucometers generally are accurate in humans. BG values were significantly lower in venous than capillary samples. The current findings show that veterinary glucometers intended for companion-animal species are inappropriate for use in the studied NHP species, whereas the human glucometers showed clinically acceptable accuracy in all 3 species. Finally, potential differences between venous and capillary BG values should be considered when comparing and evaluating results.

Self-Injurious Behavior Secondary to Cytomegalovirus-Induced Neuropathy in an SIV-Infected Rhesus Macaque (Macaca mulatta).

A 3.5-y-old, female rhesus macaque (Macaca mulatta) inoculated with SIVmac239 presented 8 mo later for inappetence and facial bruising. Physical examination revealed a superficial skin abrasion below the left eye, bruising below the left brow, and epistaxis of the left nostril. There were no significant findings on CBC, serum chemistry, urinalysis, or radiographs. Differential diagnoses included infectious etiologies, self-injurious behavior, immune-mediated dermatitis, and neoplasia. Lack of response to antibiotic and analgesic therapy and observations of the macaque made it apparent that the skin lesions were self-inflicted. The excoriations rapidly progressed to extend over the nose, and the left palpebrae became edematous. Euthanasia was elected because the macaque appeared to be experiencing continued discomfort despite analgesic therapy. Histopathologic examination revealed systemic cytomegalovirus (CMV) infection involving the facial nerves, periocular nerves, meninges, and perimesenteric lymph nodes. CMV is a common infection in macaques, with adult seroprevalence close to 100% in most colonies. Infection in immunocompetent animals is usually asymptomatic but can cause significant clinical disease in immunodeficient hosts. CMV is associated with a painful peripheral neuropathy in human AIDS patients, and analgesic treatment is often unsatisfactory. Peripheral neuropathy secondary to CMV should be considered as an underlying cause of self-injurious behavior in SIV-infected macaques. Macaques affected by other diseases and disorders may also be at risk for development of painful peripheral neuropathies.

Extraintestinal campylobacteriosis in rhesus macaques (Macaca mulatta).

Two cases of clinical disease associated with extraintestinal Campylobacter infection were recently encountered in rhesus macaques (Macaca mulatta). The first case was that of a 3-y-old, male, rhesus macaque experimentally infected with SIV, who presented with abdominal pain and a midabdominal mass and was euthanized. Pathology findings included an abscess within the median liver lobe, fibrinopurulent peritonitis, and intestinal serositis with isolation of Campylobacter fetus from the blood, liver, and the hepatic abscess. The second case was that of a 1-mo-old, female, rhesus macaque who died with no apparent history of illness. Gross pathology findings included thin body condition and diarrheic staining of the perineum; histologically, acute multifocal hepatitis with intralesional bacteria was noted. Campylobacter coli was isolated from the liver and colon. Extraintestinal Campylobacter infection is uncommon in humans, usually occurring in immunocompromised subjects and most commonly manifesting as bacteremia. Extraintestinal Campylobacter infections in animals are rare but have been associated with bacteremia and cholecystitis. The macaques presented here were either immunocompromised due to SIV infection (case 1) or more vulnerable due to young age (case 2). These factors likely contributed to the extraintestinal spread of Campylobacter.