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virus with genes from the less virulent Clade IIa virus. The project was conceived and approved years before the recent mpox outbreak, and it does not include any studies with the circulating Clade IIb virus.
When the sub-project was proposed in 2015, the proposed experiments were subject to a rigorous review process and were subsequently approved. Since 2009, mpox research within the NIAID intramural program has been registered with the FSAP. As required by the FSAP, the NIAID intramural program FSAP registration was updated to reflect the mpox research when the experiments were approved. During FSAP inspections, all NIH IBC-related documents and minutes are reviewed. This work would not meet the definition of a restricted experiment and was not reviewed by the Intragovernmental Select Agents and Toxins Technical Advisory Committee (ISATTAC), all strains created were inventoried and treated as select agents, and the FSAP did not determine ISATTAC review was required based on the project description and detail included in our select agent registration.
After the approval of the proposed experiments in the mpox sub-project investigating clade differences, NIAID investigators generated chimeric viruses by replacing certain genes of Clade I mpox virus with the corresponding genes of Clade IIa virus and infecting an appropriate mouse model with them to determine if any of the genetic changes could decrease the severity of mpox disease caused by the Clade I virus. To date, these experiments have not identified the genetic underpinnings of the observed increased pathogenicity of the Clade I mpox viruses, indicating that further research is necessary to determine these critical genetic factors.
Throughout these experiments, all viruses—including the new chimeric viruses—were handled and inventoried as select agents, and all work with select agent strains was performed in compliance with the requirements in the Federal Select Agent Regulations and NIH policies regarding biological materials. For these experiments, all live viruses were handled at a Biosafety Level 3 (BSL-3) laboratory, in select agent registered facilities, by personnel with approved security risk assessments, and with approval through the NIH Biological Surety Program.[1] While the experiments were subject to the Federal Select Agent Regulations, including registration of planned recombinant work, none of the experiments meet the definition of a restricted experiment as outlined in Federal regulations.[2]
As stated above, the September 2022 Science article noted in your letter referenced a potential sub-project, which your letter refers to as the “clade I study,” that has not been formally proposed. This potential sub-project would include the generation of chimeric viruses by replacing genes in the less virulent Clade IIa virus with those in the more virulent Clade I virus. To reiterate, NIAID has no plans to move forward with this research. As detailed above, this type of research would require a formal proposal to be submitted for review, and the proposal would need to undergo the rigorous review process described in this letter before it could be initiated. This review process would specifically include an assessment of whether the research may be subject to the HHS P3CO Framework.
- ↑ NIH Policy Manual — Chapter 3037. https://policymanual.nih.gov/3037
- ↑ Code of Federal Regulations. 42 CFR Part 73.13. https://www.ecfr.gov/current/title-42/chapter-I/subchapter-F/part-73/section-73.13
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