Parainfluenza virus 5 (PIV5), formerly known as simian virus 5 (SV5), is a paramyxovirus often referred to as canine parainfluenza virus (CPI) in the veterinary field. PIV5 is thought to be a contributing factor to kennel cough. Kennel cough vaccines containing live PIV5 have been used in dogs for many decades. PIV5 is not known to cause any diseases in humans or other animals. PIV5 has been used as a vector for vaccine development for humans and animals. One critical question concerning the use of PIV5 as a vector is whether prior exposure to PIV5 would prevent the use of PIV5-based vaccines. In this work, we have examined immunogenicity of a recombinant PIV5 expressing hemagglutinin (HA) of influenza A virus subtype 3 (rPIV5-H3) in dogs that were immunized against PIV5. We found that vaccination of the dogs containing neutralizing antibodies against PIV5 with rPIV5-H3 generated immunity against influenza A virus, indicting that PIV5-based vaccine is immunogenic in dogs with prior exposure. Furthermore, we have examined exposure of PIV5 in human populations. We have detected neutralizing antibody (nAb) against PIV5 in 13 out of 45 human serum samples (about 29 percent). The nAb titers in humans were lower than that in vaccinated dogs, suggesting that nAb in humans is unlikely to prevent PIV5 from being an efficacious vector in humans.

BackgroundRabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.Methodology/Principal FindingsNon-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico) correlates with the presence of high level of virus neutralizing antibodies (VNA) in the cerebral spinal fluid (CSF) and mild immune cell accumulation in the central nervous system (CNS). By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.Conclusions/SignificanceNon-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

Rhesus macaques (Macaca mulatta) are the most commonly used NHP in biomedical research. 19 Their physiologic similarity to humans makes them an appealing model to study a variety of human conditions such as aging, reproduction, development, and neurology. 28 NHP facilities, especially those with outdoor housing, may house 5000 macaques or more at once. Considering that rhesus macaques are an aggressive and agonistic species, 37 animals experience traumatic injuries relatively commonly, especially with high-density group housing. One study at a national primate research center calculated that the percentage of animals presenting to the facility's hospital with injuries requiring sutures ranged from 5% to 9% annually. 23 In addition to encounters with conspecifics resulting in trauma, many studies using rhesus macaques have the potential to cause temporary pain or discomfort; therefore, adequate analgesia should be provided unless scientifically justified otherwise, as required by the Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act and Regulations. 2,3,21 Opioids play an integral part when developing pain management plans for NHP in research. In NHP medicine, opioids are often combined with NSAID as multimodal analgesia for perioperative and postoperative care, in addition to providing adequate pain control for animals that have sustained moderate to severe injuries. 4 In addition, opioids are considered when NSAID are contraindicated, for example, during gestation, due to project needs, and in animals having compromised liver or kidney function. 27 Despite the significance of opioids in pain management, the current human opioid epidemic has caused withdrawal of these drugs from the market, thus severely affecting veterinary medicine. 10 This shortage has driven clinicians to explore other opioid options, such as new formulations and different dosing regimens. 9 Buprenorphine is currently one of the most frequently prescribed opioid analgesics used by NHP facilities for the treatment of moderate acute and chronic pain. 32 It is a partial µ-agonist, κ-antagonist with high affinity for the µ-receptor and a slow dissociation rate. 25,34 These properties are responsible for the long half-life of buprenorphine and its ability to displace other µ-agonists, such as morphine, when given concomitantly. In addition, the ability of this analgesic to bind partially to the µ-receptor creates a ceiling effect; therefore, increasing

Measles virus causes a highly infectious disease in NHP. Clinical signs range from asymptomatic to fatal, although measles virus is most well-known for its characteristic generalized maculopapular rash. Along with appropriate quarantine practices, restricted human access, and appropriate personal protective equipment, vaccines are used to combat the risk of infection. The canine distemper-measles vaccine (CDMV), administered at the manufacturer's standard dose (1.0 mL IM), has been shown to be effective against clinical measles disease in rhesus macaques (Macaca mulatta). The goal of the current study was to test whether doses smaller than the manufacturer's recommended dose stimulated adequate antibody production to protect against infection. We hypothesized that either 0.25 or 0.5 mL IM of CDMV would stimulate antibody production comparable to the manufacturer's recommended dose. We found that the 0.25-mL dose was less effective at inducing antibodies than either the standard (1.0 mL) or 0.5-mL dose, which both yielded similar titers. The primary implication of this study informs balancing resource allocation and providing efficacious immunity. By using half the manufacturer-recommended dose, the 50% cost reduction may provide sufficient monetary incentive to implement, maintain, or modify measles vaccination programs at NHP facilities.

A female rhesus macaque developed two episodes of generalized convulsions during transcutaneous spinal cord stimulation (TSCS) and urodynamic studies under ketamine anesthesia. The seizures took place in the absence of active TSCS and bladder pressure elevation. Ketamine anesthesia remains the primary risk factor for the convulsions during these experimental procedures.