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The NIH Institutional Biosafety Committee (IBC)[1] formally reviews any NIH intramural research proposing to use recombinant and/or synthetic nucleic acid molecules in accordance with the NIH Guidelines, in the context of research involving potentially infectious human, plant, or animal materials; human pathogens; and human and non-human primate blood, tissues, and body fluids, including primary human cell cultures. The NIH IBC also determines the required biosafety level and biocontainment measures for any proposed research during this review. Such proposed research then undergoes review by any other appropriate entities, including the Dual Use Research of Concern (DURC) Institutional Review Entity (IRE), if appropriate.
The DURC-IRE is the NIL authority for the oversight and evaluation for proposed research that may fall under the Department of Health and Human Services’ (HHS) Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (HHS P3CO Framework).[2] As noted in the HHS P3CO Framework, proposed intramural and extramural life sciences research that is being considered for funding and that has been determined by the funding agency as reasonably anticipated to create, transfer, or use enhanced potential pandemic pathogens is subject to additional HHS department-level review.
NIH research involving select agent strains and recombinant work is always performed in close collaboration with the Federal Select Agent Program (FSAP)—which is managed jointly by the Centers for Diseases Control and Prevention and the Department of Agriculture[3]—and the entity Responsible Official to ensure compliance with applicable regulations and subjected to any reviews FSAP deems appropriate.
Your letter inquired about research involving the mpox virus. By way of background, the mpox virus is made up of two genetically distinct clades. Clade I mpox viruses, endemic in the Congo Basin, cause more severe disease than the Clade II mpox viruses, which are endemic to Western Africa. The Clade II mpox virus also consists of two subclades—Clade IIa and IIb. The current global mpox outbreak is driven by a Clade IIb virus, but circulation of both Clade I and Clade IIa in Africa presents an ongoing risk of future regional and global outbreaks of these viruses. The genetic basis for the variability in disease outcomes of the two clades is unknown. Additional research to identify the viral components that account for the observed differences in mpox disease severity between the two clades could help determine key targets within the mpox virus genome for the development of medical countermeasures.
Your letter also referenced a specific NIAID intramural project—Poxvirus Host Interactions, pathogenesis and immunity, 1ZIAAI000979. This project includes research on several orthopoxviruses including vaccinia virus, cowpox virus, and mpox virus. The mpox projects include development of a small animal model, investigation of the basis for mpox pathogenicity, assessment of mpox vaccines, and analysis of mpox clade differences. One approach to studying mpox clade differences was proposed and approved in 2015 and involves the generation of chimeric viruses—viruses that incorporate genes from two mpox strains. This ongoing sub-project includes only chimeric viruses created by replacing genes in the more virulent Clade I
- ↑ NIH Policy Manual — Chapter 3035. https://policymanual.nih.gov/3035
- ↑ HHS Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens. https://www.phe.gov/s3/dualuse/documents/p3co.pdf
- ↑ Federal Select Agent Program. https://www.selectagents.gov/
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