Additional ACTIV Preclinical Resources
The ACTIV Preclinical Working Group has also produced the following sources to help researchers develop their COVID-19 projects:
1. Field Guide: Considerations for the Use of Primate Models for SARS-CoV-2 Treatments and Vaccines
SARS-CoV-2 burst onto the medical and scientific stage in late 2019,
a novel coronavirus that has taken the world by storm. One
of the most important activities in understanding virus infectivity,
life cycle, and pathogenicity of a new virus involves the use of animal models.
As investigators in academics and in the scientific industry grapple with developing effective therapies
and vaccines, it is critical to understand how different animal models may provide valuable information
to inform the science. This Nonhuman Primate Field Guide is designed as a companion
to the Small Animal Field Guide. The purpose of the Nonhuman Primate Field Guide is to inform investigators
of the current status of nonhuman primate (NHP) models, the availability of resources to perform studies,
and to provide some details about experimental design and sampling to guide scientific planning.
2. Field Guide: Best Practices for COVID-19 Research in Small Animal Models
The small animal model videos are a compendium of world expert guidance on best practices for the use of small animal models for COVID 19 research.
The videos were developed in an effort to support harmonization of best practices for the use of small animal models.
Since SARS-COV-2 was first reported in late 2019, researchers around the world shifted gears to conduct COVID-19 studies.
However, limited resources, including BSL 3 /4 facilities and COVID-19 animal models, have prompted an effort to harmonize
and streamline guidance to make the best use of available biomedical research resources and facilitate interpretation
and comparison of the results across studies. Using the Small Animal Model Field Guide and these videos as a guide,
researchers will be able to improve harmonization and make the best use of available biomedical research resources.
3. Accelerated Preclinical Paths to Support Rapid Development of COVID-19 Therapeutics
When SARS-CoV-2 emerged at the end of 2019, no approved therapeutics or vaccines were available.
An urgent need for countermeasures during this crisis challenges the current paradigm
of traditional drug discovery and development, which usually takes years from start to finish.
Approaches that accelerate this process need to be considered. Here we propose the minimum data package required
to move a compound into clinical development safely. We further define the additional data
that should be collected in parallel without impacting the rapid path to clinical development.
Accelerated paths for antivirals, immunomodulators, anticoagulants
and other agents have been developed and can serve as "roadmaps" to support prioritization of compounds
for clinical testing. These accelerated paths are fueled by a skewed risk-benefit ratio and are necessary
to advance therapeutic agents into human trials rapidly and safely for COVID-19.
Such paths are adaptable to other potential future pandemics.
4. ACTIVating Resources for the COVID-19 Pandemic: In vivo Models for Vaccines and Therapeutics
The Preclinical Working Group of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV),
a public-private partnership spearheaded by the National Institutes of Health,
was charged with identifying, prioritizing, and communicating SARS-CoV-2 preclinical resources.
Reviewing SARS-CoV-2 animal model data facilitates standardization and harmonization
and informs knowledge gaps and prioritization of limited resources. To date, mouse, hamster, ferret,
guinea pig, and non-human primates have been investigated. Several species are permissive for SARS-CoV-2 replication,
often exhibiting mild disease with resolution, reflecting most human COVID-19 cases. More severe disease develops
in a few models, some associated with advanced age, a risk factor for human disease.
This review provides a snapshot that recommends the suitability of models for testing vaccines and therapeutics,
which may evolve as our understanding of COVID-19 disease biology improves. COVID-19 is a complex disease
and individual models recapitulate certain aspects of disease; therefore, the coordination and assessment
of animal models is imperative.