Smallpox's Return Would Cause Global Concerns

An ad hoc committee under the National Academies of Sciences, Engineering, and Medicine announced a study that analyzed the lessons derived from the recent pandemic and the mpox multi-country outbreak.

The Future State of Smallpox Medical Countermeasures report argues that the United States and the global community should prepare for smallpox to make an unfortunate return. 

According to the report, smallpox could return through an accidental leak or even an intentional act.

This study evaluated the current state of research, development, and stockpiling of smallpox medical countermeasures (MCMs).

The report also states that preparing for the return of smallpox is key to preventing the spread of other diseases caused by viruses within the Orthopoxvirus genus.

Smallpox, a disease that killed an estimated 500 million people in the 20th century alone, is the only human disease to be eradicated.

Since a monkey was identified in 1958 and a human in 1970, mpox virus-associated outbreaks have occurred primarily in Central and West Africa.

Since May 2022, an outbreak of mpox Clade 2b virus has impacted many countries, while Clade 1 has significantly impacted central Africa in 2024.

However, the country of Cameroon is an exception, as both clades concurrently circulate.

Dr. Zhilong Yang, an associate professor in the Texas A&M School of Veterinary Medicine & Biomedical Sciences Department of Veterinary Pathobiology, served on the committee that produced the report, commented in a press release on April 12, 2024, "Smallpox vaccines and drugs also hold the promises and potentials to prevent and treat mpox and other viruses within the same family of smallpox virus, which is another important reason that we should continue to research poxviruses and develop smallpox medical countermeasures, including diagnostics, vaccines, and therapeutics."

Only two laboratories, including the U.S. Centers for Disease Control and Prevention (CDC), have official collections of the virus that causes smallpox, making the chance of an accidental leak minimal.

However, there are enough publicly available genetic sequences of the smallpox virus to make it possible to recreate it, especially with the advancement of synthetic biology and artificial intelligence.

"Even one smallpox outbreak would be a huge global issue, so we must stay vigilant," Dr. Yang added.

"Scientists and medical professionals must also be aware that smallpox symptoms are very similar to diseases like mpox, which have been prevalent more recently. If there is a smallpox outbreak, we must quickly recognize it."

In November 2021, the U.S. CDC vaccine committee unanimously voted in favor of Bavarian NNordic's JYNNEOS® (MVA-BN®, IMVAMUNE®) vaccine as an alternative to the second-generation ACAM2000® vaccine for primary and booster doses against smallpox. 

As of April 2024, healthcare providers in the U.S. can order JYNNEOS through distributors to make it commercially available for at-risk individuals at local pharmacies, physician offices, and public health clinics.