Opportunities for Refinement of Non-Human Primate Vaccine Studies

Abstract

Non-human primates (NHPs) are used extensively in the development of vaccines and therapeutics for human disease. High standards in the design, conduct, and reporting of NHP vaccine studies are crucial for maximizing their scientific value and translation, and for making efficient use of precious resources. A key aspect is consideration of the 3Rs principles of replacement, reduction, and refinement. Funders of NHP research are placing increasing emphasis on the 3Rs, helping to ensure such studies are legitimate, ethical, and high-quality. The UK’s National Centre for the 3Rs (NC3Rs) and the Coalition for Epidemic Preparedness Innovations (CEPI) have collaborated on a range of initiatives to support vaccine developers to implement the 3Rs, including hosting an international workshop in 2019. The workshop identified opportunities to refine NHP vaccine studies to minimize harm and improve welfare, which can yield better quality, more reproducible data. Careful animal selection, social housing, extensive environmental enrichment, training for cooperation with husbandry and procedures, provision of supportive care, and implementation of early humane endpoints are features of contemporary good practice that should and can be adopted more widely. The requirement for high-level biocontainment for some pathogens imposes challenges to implementing refinement but these are not insurmountable.

Harmonisation of welfare indicators for macaques and marmosets used or bred for research

“…Within infectious disease, more than half of the indicators (33/56) were considered valid and reliable by three-quarters of respondents, with over 40% (14/33) of these being cage-based. Appetite, body weight, and mortality are in the top five, reflecting that many of the macaques used in such studies will experience disease (Prescott et al, 2021). Additionally, to round out the top five are stereotypy and self-harm behaviour.…”

“…Welfare assessment is also a component of the scientific method, because physiological and psychological responses to suffering can significantly affect data quality (Poole, 1997;Institute for Laboratory Animal Research, 2008). Minimising avoidable suffering is therefore necessary to ensure the validity of the scientific research performed (Novak & Petto, 1991;Graham & Prescott, 2015;Hannibal et al, 2017;Prescott et al, 2021).…”

Harmonisation of welfare indicators for macaques and marmosets used or bred for research

“…Within infectious disease, more than half of the indicators (33/56) were considered valid and reliable by three-quarters of respondents, with over 40% (14/33) of these being cage-based. Appetite, body weight, and mortality are in the top five, reflecting that many of the macaques used in such studies will experience disease ( Prescott et al ., 2021 ). Additionally, to round out the top five are stereotypy and self-harm behaviour.…”

“…Welfare assessment is also a component of the scientific method, because physiological and psychological responses to suffering can significantly affect data quality ( Poole, 1997 ; Institute for Laboratory Animal Research, 2008 ). Minimising avoidable suffering is therefore necessary to ensure the validity of the scientific research performed ( Novak & Petto, 1991 ; Graham & Prescott, 2015 ; Hannibal et al ., 2017 ; Prescott et al , 2021 ).…”

Improving rigor and reproducibility in nonhuman primate research

“…We next highlight specific lessons learned from a number of disciplines that use the NHP model at the National Primate Research Centers (NPRCs), with the goal of expanding these best practices to the wider biomedical research community. Rigor and reproducibility in NHP research have been addressed in a recent NIH workshop (https:// osp.od.nih.gov/wp-content/uploads/NHP_Workshop_Report_ FINAL_20200218.pdf), and some of these considerations with respect to NHP vaccine studies, in particular, have been recently discussed (Prescott et al, 2021).…”