Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colonystimulating factor were administered by the respiratory route to rhesus monkeys-in which HPIV3 infection is mild and asymptomatic-and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV) and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s). In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera (Cricetomys, Graphiurus, Funisciurus) shown to be infected with MPXV. Here, we examine the course of MPXV infection in Cricetomys gambianus (pouched Gambian rats) and this rodent species’ competence as a host for the virus. We obtained ten Gambian rats from an introduced colony in Grassy Key, Florida and infected eight of these via scarification with a challenge dose of 4X104 plaque forming units (pfu) from either of the two primary clades of MPXV: Congo Basin (C-MPXV: n = 4) or West African (W-MPXV: n = 4); an additional 2 animals served as PBS controls. Viral shedding and the effect of infection on activity and physiological aspects of the animals were measured. MPXV challenged animals had significantly higher core body temperatures, reduced activity and increased weight loss than PBS controls. Viable virus was found in samples taken from animals in both experimental groups (C-MPXV and W-MPXV) between 3 and 27 days post infection (p.i.) (up to 1X108 pfu/ml), with viral DNA found until day 56 p.i. The results from this work show that Cricetomys gambianus (and by inference, probably the closely related species, Cricetomys emini) can be infected with MPXV and shed viable virus particles; thus suggesting that these animals may be involved in the maintenance of MPXV in wildlife mammalian populations. More research is needed to elucidate the epidemiology of MPXV and the role of Gambian rats and other species.

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Preparing for the wide variety of disasters that can occur is challenging for any animal research facility, but the level of concern for human and animal health rises significantly when infectious agents and toxins are part of the scenario. Federal regulations provide detailed requirements for the development of an incident response plan (IRP) when select agents and toxins (SATs) are used. In addition to the usual issues associated with disaster planning, the IRP must address concerns associated with the potential theft, loss, or release of SATs that may affect both institutional personnel and the surrounding community. The level of detail in the IRP and the intensity of training should be appropriate for the level of risk involved. Regulations describe certain basic requirements but do not address the risks of SAT-exposed animals, which have been the subject of additional guidance to help implement regulatory requirements. A 2008 joint publication of the Centers for Disease Control and Prevention and the Animal and Plant Health Inspection Service describes scenarios in which SAT-exposed animals are handled in the same manner as the agent or toxin itself for the purpose of reporting a SAT theft, loss, or release. Events that resulted from the impact of Hurricane Ike at the University of Texas Medical Branch in Galveston provide a valuable opportunity to evaluate the effectiveness of the federal regulations and to build on lessons learned from this disaster. These lessons can help to supplement the regulatory requirements and improve the safety and security of handling both SATs and animals exposed to them during and after an emergency situation.