Researchers at the Yale School of Public Health have developed a sequencing approach for the human mpox virus that builds upon the genome sequencing methods that were so essential during the COVID-19 pandemic. Their work demonstrates how whole genome sequencing can be to be used for the surveillance of another emerging infectious disease.
The YSPH team and their colleagues began adapting SARS-CoV-2 sequencing for use with the human mpox virus following the detection of mpox cases in non-endemic countries in late May 2022. Mpox virus is a zoonotic DNA virus endemic to western and central Africa. Mpox was formerly known as monkeypox.
“We developed a sequencing approach for use with mpox clinical specimens and made our protocol public on July 15, 2022,” said Nicholas F.G. Chen, MPH ’23, who conducted his research as a member of the Grubaugh Lab. Chen, whose degree is in Epidemiology of Microbial Diseases with a concentration in Public Health Modeling, is one of the co-first authors of a research article in Plos Biology detailing the team’s findings. Chantal B.F. Vogels, research scientist in epidemiology (Microbial Diseases) and also of the Grubaugh Lab, is one of the co-senior authors.
The other co-first authors are Chrispin Chaguza, associate research scientist in Epidemiology (Microbial Diseases), and Luc Gagne of the Massachusetts Department of Public Health. The co-senior author is Glen Gallagher of the Massachusetts Department of Public Health and Rhode Island Department of Health.
"Our team quickly developed a human monkeypox virus-specific primer scheme that can be ‘plugged’ into existing sequencing methods that many labs established during the SARS-CoV-2 pandemic,” said Vogels. “By partnering with the Massachusetts Department of Public Health, we were able to quickly validate the primer scheme and share it with other public health labs across the country and internationally. This collaboration between academic and public health labs enabled us to quickly respond to a new public health emergency.”
Pathogen whole genome sequencing, which was used extensively during the COVID-19 pandemic, can provide insights into the spread, evolution, and characteristics of pathogens. “Pathogen sequencing is used most notably to detect and understand the emergence of viral variants,” said Chen. Large-scale investments into pathogen sequencing infrastructure throughout the world during the pandemic has accompanied an increased focus on pathogen sequencing, he said.
To expedite a rapid public health response to mpox, the researchers advertised their findings to public health and research laboratories on social media and then sent their primer scheme to 40 public health and research labs.
“Of these, 10 labs located across the U.S., U.K., Portugal, and Brazil provided data on the performance of our approach across a range of sample types, sample viral concentrations, and sequencing platforms,” Chen said. “With this data, we show that our approach can be successfully implemented across a variety of laboratory and resource settings.”
By leveraging existing SARS-CoV-2 sequencing infrastructure, the researchers show that their approach can be quickly and easily integrated into many of the genomic surveillance networks developed during the pandemic, Chen said.
The approach that the team developed has since been used to detect mutations that affect diagnostic analysis and antiviral effectiveness.
“We show that our sequencing approach can provide a rapidly deployable, cost-effective, and flexible approach to pathogen whole genome sequencing in response to newly emerging pathogens,” Chen said.
Initially rare outside endemic countries, mpox recently emerged as a global threat. The virus was first detected in the United Kingdom on May 7, 2022, quickly spreading to other continents through travel-related infections and sometimes unknown transmission chains.
“As of January 5, 2023, 84,075 cases of mpox across 103 non-endemic countries have been reported, often with atypical clinical presentations,” the team reported in its research article. “The lack of consistent clinical presentations, unknown transmission dynamics, and uncertainty surrounding animal reservoirs highlights the importance of establishing rapid genomic surveillance networks.”