On July 21, 2022, the White House Office of Science and Technology Policy published the U.S. Monkeypox Research Priorities to speed science and accelerate the domestic and global monkeypox outbreak response. Publicly identifying research priorities will energize scientific communities to reduce critical gaps in our knowledge regarding monkeypox.
U.S. government departments and agencies, with international allies and partners, are accelerating efforts to answer critical monkeypox research questions to inform the outbreak response and strategically planning to launch further research. Insights from this work will guide swift action during this public health emergency.
Ongoing U.S. Government-supported domestic and global monkeypox research activities include:
- Conducting epidemiologic and clinical observational studies and modeling:
- The Centers for Disease Control and Prevention (CDC) is launching observational studies to examine epidemiological characteristics, the clinical course of the illness, and potential transmission routes in a congregate setting in Illinois and among persons receiving PEP++ in a large metropolitan area on the east coast. These studies started recruiting in early August. Additional studies are planned and more will be added to meet outbreak need.
- In collaboration with the Washington, D.C. Department of Health, the CDC is providing technical assistance to study transmission dynamics through network analysis and detailed contact tracing.
- Starting in early June, CDC initiated epidemiological and medical countermeasure (MCM) modeling to examine outbreak dynamics and MCM impacts on transmission in different deployment scenarios.
- Developing new serological tools: The National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Disease (NIAID) is developing a high throughput serologic assay, which can distinguish between individuals who have been infected with a poxvirus versus individuals who were vaccinated against smallpox.
- Conducting serological surveys to better understand transmission: The NIH/NIAID and CDC are conducting retrospective serological surveys involving research specimens collected during existing clinical research programs – conducted for other purposes – that span non-overlapping geographic areas, to better understand how long and where the virus has been potentially circulating in the United States. CDC also initiated a prospective serosurvey in collaboration with the San Francisco Department of Public Health on June 27.
- Conducting vaccine and therapeutic clinical trials: NIH/NIAID is standing up clinical trials to answer critical efficacy and safety questions around monkeypox therapeutics and vaccines to better understand how to most effectively deploy this outbreak toolkit for the response.
- Tecovirimat (TPOXX) randomized controlled trials:
- Democratic Republic of the Congo (DRC): NIH/NIAID, in collaboration with Institut National de Recherche Biomédicale of the DRC, is launching a double-blind, randomized controlled trial of the safety and efficacy of TPOXX for the treatment of adult and pediatric patients diagnosed with monkeypox.
- United States: NIH/NIAID is initiating a Phase 3 double-blind, randomized controlled trial of TPOXX for the treatment of monkeypox virus in the outpatient setting in the United States through the AIDS Clinical Trials Group. The study also will include an open-label cohort to ensure that certain high-risk populations (e.g., pregnant or breastfeeding individuals and those with severe immune-deficiencies) do not get randomized to placebo, while also providing a means to collect important data on the safety and pharmacokinetics of TPOXX in these populations.
- Monitoring monkeypox virus assays and developing positive controls: The National Institute of Standards and Technology (NIST) rapidly developed a research-grade monkeypox virus positive control to help users and manufacturers of monkeypox diagnostic tests assess that their tests are properly working. The CDC is continuously monitoring the performance characteristics of routine and specialized molecular assays for monkeypox virus detection.
- Next-generation orthopoxvirus therapeutics: Biomedical Advanced Research and Development Authority (BARDA) continues to support Biofactura to develop a monoclonal antibody (mAb) product for the smallpox indication, which will be evaluated in non-clinical studies. MAbs have the potential to serve as safe and effective countermeasures for special populations or to address orthopoxviruses resistant to approved therapeutics.
- Expanding wastewater surveillance to track monkeypox virus: The CDC National Wastewater Surveillance System is adding monkeypox virus tracking to some of its sites in the United States that were initially utilized to track SARS-CoV-2 for the COVID-19 pandemic.
- Evaluating monkeypox virus sequences through genomic analyses: The CDC, in collaboration with partners, is sequencing specimens submitted for testing that are both anticipated to be epidemiologically informative and have sufficient DNA quantity (~17%). These studies will inform understanding of virus circulation, identify new variants, and improve overall monkeypox genome interpretation.
- Nigeria is leveraging its U.S. President’s Emergency Plan for AIDS Relief (PEPFAR)-supported laboratory systems to diagnose and sequence endemic monkeypox.
- Examining global human-animal interfaces and potential animal reservoir species:
- The NIH/NIAID is conducting ecological studies in the Republic of the Congo to understand the monkeypox human-animal interface and to investigate suspect reservoir hosts such as Gambian pouch rats, rope squirrels, and dormice.
- The CDC is also conducting One Health research activities and ecological studies in DRC, Cameroon, and Nigeria to evaluate potential wild animal reservoir species and study interactions at critical human-animal interfaces.
- Strengthening global monkeypox surveillance and response activities:
- The Department of Defense’s Defense Threat Reduction Agency has engaged with several partner countries to mitigate the threat posed by monkeypox by providing monkeypox-related training to 70 animal and human health staff in Cameroon and 120 staff in Nigeria. Further monkeypox epidemiology, ecology, and detection training will be conducted in Cameroon, Nigeria, and Gabon. Investigators with NIH/NIAID’s Centers for Research in Emerging Infectious Diseases are supporting clinical surveillance in DRC, Nigeria, and Sierra Leone, and providing validated primers and probes to strengthen diagnostic capacity in Kenya, Tanzania, Panama, and Brazil.
- PEPFAR works in 55 countries and is engaging its human resources; surveillance and diagnostic platforms; and sample transportation, data, and waste management and biosafety systems to support monkeypox diagnostics, including in many endemic countries (Benin, Cameroon, Cote d’Ivoire, DRC, Ghana, Liberia, Nigeria, Sierra Leone, and South Sudan).
- Building capacity to safely and effectively prevent, detect, and respond to monkeypox in endemic and non-endemic countries: PEPFAR is leveraging its laboratory, surveillance and public health, and community infrastructure and programming to help prevent and respond to monkeypox in many endemic countries. In addition, PEPFAR teams are utilizing existing community and public health networks, as appropriate, for risk communication and prevention messaging to those populations most at-risk of monkeypox. The Department of State’s Bureau of International Security and Nonproliferation works with partners around the world to strengthen biosafety and biosecurity capacity to support safe and secure detection of, and response to, monkeypox.
While these studies are poised to generate knowledge that will accelerate the global monkeypox response effort, further research is needed to fill priority gaps. This includes conducting observational and randomized vaccine and therapeutic studies, assessing viral detection in different fluids and parts of the body, evaluating viral viability in various environments, further transmission studies, better characterizing perspectives of affected populations to strengthen public health communication and other interventions, evaluating equitable distribution and improving access to monkeypox countermeasures, and balancing outbreak response in non-endemic countries with those in endemic countries. Ultimately, outbreak response must ensure that everyone can be protected and the knowledge gained from such research has the potential to benefit Americans and affected partners around the world.
Just as the monkeypox outbreak continues to evolve, monkeypox research priorities and activities must be dynamic and refined to reflect the current stage of the outbreak and emerging response needs. Consequently, this list of ongoing activities in not exhaustive and will be updated to reflect the current landscape of monkeypox related research.