Page:Interim Staff Report on Investigation into Risky MPXV Experiment at the National Institute of Allergy and Infectious Diseases.pdf/54

As prepared Bernard Moss, MD, PhD

Good afternoon. My name is Bernard Moss. I am an Investigator and Section Chief in the National Institute of Allergy and Infectious Diseases. I joined NIAID as a Medical Officer in 1966. For more than 50 years I have investigated the biology and host interactions of poxviruses including mpox for the last 15 years.

My current mpox research has two major goals.

The first, which has taken precedence since the 2022 outbreak of mpox, is to develop improved vaccines using mRNA and protein lipid nanoparticles. I am happy to say that the mRNA vaccine is now recruiting subjects for a clinical trial.

The second and longer-term goal is to determine the genetic basis for the difference in virulence of mpox virus clades. Such information could open new opportunities for managing and treating mpox and predicting the impact of new strains should they arise.

To achieve both goals, we developed a small animal model that mimics the severity of disease caused by mpox virus in humans (clade I>IIa>II2bIIb [sic]). My laboratory previously developed ways of deleting and replacing genes of vaccinia virus, the prototype poxvirus used as the smallpox vaccine. Such studies had allowed us to determine the roles of genes involved in virus replication and host interactions using a mouse model.

Similarly, I am now investigating the genetic basis for differences in the virulence of clade I and clade IIa mpox virus by replacing genes of the clade I virus with genes of a clade IIa virus. I want to emphasize that clade IIa viruses have caused few human mpox cases in Africa and human-to-human transmission has never been reported anywhere, in contrast to the clade I and clade IIb current outbreak strain.

Following institutional approval, we began to replace genes of the virulent clade I with the corresponding genes of clade IIa, with the expectation that virulence of the chimeric virus would be less than that of clade I. Since there is evidence for human-to-human transmission of clade I, but none for clade IIa, the expectation is that the chimeric virus would also be less transmissible.

To date, we have exchanged approximately 50 of the 200 genes but have seen no effect on virulence. We are considering three main possibilities: (1) we have not yet exchanged the individual genes most important for the difference in virulence, (2) virulence is due to multiple genes acting together, or (3) two or more genes have redundant functions. Replacement of additional clade I genes will be necessary to evaluate these possibilities.

Depending on the results of those experiments, I will consider additional gene exchanges that might include transfers in the opposite direction or involve clade Ilb. I have not planned or proposed such experiments for approval since we have not completed the current experiments and therefore do not yet know which genes might be best to transfer. However, should it appear in the future that such an experiment would greatly contribute to understanding the basis for