Maximum-containment laboratories are a unique and essential component of the bioeconomy of the United States. These facilities play a critical role in the national infrastructure, supporting research on a select set of especially dangerous pathogens, as well as novel, emerging diseases. Understanding the ecology, biology, and pathology at the human-animal interface of zoonotic spillover events is fundamental to efficient control and elimination of disease. The use of animals as human surrogate models or as target-host models in research is an integral part of unraveling the interrelated components involved in these dynamic systems. These models can prove vitally important in determining both viral- and host-factors associated with virus transmission, providing invaluable information that can be developed into better risk mitigation strategies. In this article, we focus on the use of livestock in maximum-containment, biosafety level-4 agriculture (BSL-4Ag) research involving zoonotic, risk group 4 pathogens and we provide an overview of historical associated research and contributions. Livestock are most commonly used as target-host models in high-consequence, maximum-containment research and are routinely used to establish data to assist in risk assessments. This article highlights the importance of animal use, insights gained, and how this type of research is essential for protecting animal health, food security, and the agriculture economy, as well as human public health in the face of emerging zoonotic pathogens. The utilization of animal models in high-consequence pathogen research and continued expansion to include available species of agricultural importance is essential to deciphering the ecology of emerging and re-emerging infectious diseases, as well as for emergency response and mitigation preparedness.
ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Evaluation Program (PEP), which focuses on microbial monitoring by and for laboratory animal diagnostic laboratories, and the Genetic Reference Monitoring Program (GENRef), which provides assay-ready reference DNA for genetic testing of mouse strains. Since 2008, PEP has grown to become a truly international program with participating laboratories in 5 continents. Launched in 2016, GENRef currently distributes DNA from 12 common inbred mouse strains for use in genetic monitoring of locally inbred colonies as well as for genetic testing of stocks, particularly genetically engineered stocks, of uncertain origins. GENRef has the capacity to include additional strains as well as additional species. PEP and GENRef provide the reagents at cost, as a resource to the international scientific community, in the interest of improving research quality in an environment of growing concern for research quality, rigor, and reproducibility.
This case report discusses Type I hypersensitivity in ferrets following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inoculum, observed during a study investigating the efficacy of candidate COVID-19 vaccines. Following a comprehensive internal root-cause investigation, it was hypothesized that prior prime-boost immunization of ferrets with a commercial canine C3 vaccine to protect against the canine distemper virus had resulted in primary immune response to fetal bovine serum (FBS) in the C3 preparation. Upon intranasal exposure to SARS-CoV-2 virus cultured in medium containing FBS, an allergic airway response occurred in 6 out of 56 of the ferrets. The 6 impacted ferrets were randomly dispersed across study groups, including different COVID-19 vaccine candidates, routes of vaccine candidate administration, and controls (placebo). The root-cause investigation and subsequent analysis determined that the allergic reaction was unrelated to the COVID-19 vaccine candidates under evaluation. Histological assessment suggested that the allergic response was characterized by eosinophilic airway disease; increased serum immunoglobulin levels reactive to FBS further suggested this response was caused by immune priming to FBS present in the C3 vaccine. This was further supported by in vivo studies demonstrating ferrets administered diluted FBS also presented clinical signs consistent with a hyperallergic response, while clinical signs were absent in ferrets that received a serum-free SARS-CoV-2 inoculum. It is therefore recommended that vaccine studies in higher order animals should consider the impact of welfare vaccination and use serum-free inoculum whenever possible.
Animals have been closely observed by humans for at least 17 000 years to gain critical knowledge for human and later animal survival. Routine scientific observations of animals as human surrogates began in the late 19th century driven by increases in new compounds resulting from synthetic chemistry and requiring characterization for potential therapeutic utility and safety. Statistics collected by the United States Department of Agriculture's Animal and Plant Health Inspection Service and United Kingdom Home Office show that animal usage in biomedical research and teaching activities peaked after the mid-20th century and thereafter fell precipitously until the early 21st century, when annual increases (in the UK) were again observed, this time driven by expansion of genetically modified animal technologies. The statistics also show a dramatic transfer of research burden in the 20th and 21st centuries away from traditional larger and more publicly sensitive species (dogs, cats, non-human primates, etc) towards smaller, less publicly sensitive mice, rats, and fish. These data show that new technology can produce multi-faceted outcomes to reduce and/or to increase annual animal usage and to redistribute species burden in biomedical research. From these data, it is estimated that annual total vertebrate animal usage in biomedical research and teaching in the United States was 15 to 25 million per year during 2001-2018. Finally, whereas identification and incorporation of non-animal alternatives are products of, but not an integral component of, the animal research cycle, they replace further use of animals for specific research and product development purposes and create their own scientific research cycles, but are not necessarily a substitute for animals or humans for discovery, acquisition, and application of new (eg, previously unknown and/or unsuspected) knowledge critical to further advance human and veterinary medicine and global species survival.
In accordance with the «Aims of ICLA» (ICLA Bulletin No. 26, March 1970) the Governing Board established in 1969 a Working Party to prepare an International Nomenclature System for Outbred Animals. The members were: Professor, Dr. A. Spiegel, Federal Republic of Germany, chairman.Dr. M. Festing, United KingdomDr. K. Kondo, JapanDr. R. Loosli, SwitzerlandMr. S. Poiley, U.S.A. The nomenclature rules, completed and approved by the ICLA Governing Board on 8 December 1971, are published herewith. I am convinced that this system will bring order out of the existing chaos. The system is an offer to the world laboratory animal science, particularly the breeders and users. Editors of scientific journals, catalogues, and indices all over the world are also encouraged to require and use animal stock identification by this system for outbred animals used in experimentation. The ICLA Governing Board would have preferred to have seen an international centralization of symbol registration. However, the ICLA Secretariat has not got the capacity necessary for such a task and some practical solution to the registration problem will have to be found by the Governing Board. A final aim should then be for ICLA to publish a comprehensive world list of breeder symbols at intervals. Oslo, January 1972 Stian Erichsen Secretary-General.