OHSU researchers study recent monkeypox outbreak

Researchers suspect that the number of people infected during the recent Midwest outbreak may be higher than first reported

Researchers at Oregon Health & Science University are trying to gain a better understanding of last summer’s monkeypox outbreak. The researchers traveled to the Midwest twice during the past few months to obtain blood samples from residents exposed to the disease. A third trip is planned for December. The samples will be used to better understand the human immune system’s ability to fight monkeypox, information that will be critical for future vaccine development.

“The recent monkeypox outbreak in the Midwest provides a unique and important opportunity for medical research,” explained Mark Slifka, Ph.D., assistant scientist at the OHSU Vaccine and Gene Therapy Institute (VGTI) and an assistant scientist at the Oregon National Primate Research Center. Slifka is also an assistant professor of Molecular Microbiology and Immunology in the OHSU School of Medicine. “Blood samples provided by those infected with monkeypox and those who were exposed but remained illness-free can give us insight into how the human body fights off poxviruses, including the number one killer — smallpox. Tracking immune responses as they occur is tremendously helpful not only in learning how to develop better vaccines, but in providing us an opportunity to observe firsthand how the immune system attacks and destroys an invading pathogen. Watching how these interactions unfold over time helps us to expand our basic understanding of this complex disease.”

In addition to a better understanding of monkeypox infections, researchers at the VGTI hope to learn whether one of their theories is true: more people were infected with monkeypox during this past year’s outbreak than initially reported.

“At the time of the outbreak, fairly strict criteria were used to determine which cases were ’suspect’ and which ones could be confirmed as monkeypox infections,” Slifka said. “However, we believe there’s a strong chance that some people who were immunized against smallpox back in their childhood may have still maintained cross-reactive resistance to monkeypox infection as well. If this occurred, then monkeypox infection would have resulted in very limited disease symptoms or even no symptoms at all. If the symptoms were very mild, then no ’pox’ lesions would develop on the skin and those people may have thought they were simply suffering from the common cold or may not have even noticed that they were sick. Therefore, it is possible that some cases of monkeypox went undiscovered or were under-reported.”

To obtain blood samples for this study, OHSU scientists have already made two trips to Milwaukee, Wis., where a number of the state’s 39 suspected cases and 18 confirmed cases of monkeypox appeared. The cases were the first outbreak outside of Africa. In the past, approximately 1 percent to 10 percent of monkeypox cases were lethal. During this outbreak, however, no deaths were reported. Matthew Lewis, a veteran of the Slifka smallpox/monkeypox research team, will be headed back to Wisconsin in December to obtain yet more blood samples that will be used to analyze the immune responses mounted against these dangerous viruses.

Slifka’s lab recently released a smallpox study that revealed new information about how long immunity can last after smallpox vaccination. The researchers compared antibody and T-cell immunity levels in people who received vaccinations very recently with those who were vaccinated decades ago. They found that T-cell immunity dropped off slowly over time, but antibody immunity could typically last for a lifetime. This indicates that the smallpox vaccine may provide protection that lasts far longer than the previously accepted 3 to 5 years. Fortunately, the smallpox vaccine not only protects against the smallpox virus, but also protects against other closely related pox viruses such as cowpox, camelpox and monkeypox.

The smallpox virus is extinct in nature, so it remains difficult to know what level of immunity is required for full protection. People who received smallpox vaccinations and were later exposed to monkeypox during the Wisconsin outbreak, however, may provide evidence of whether protective antiviral immunity was maintained since childhood. In their current study, Slifka and his colleagues are tracking monkeypox exposure in people previously vaccinated for smallpox and comparing their disease symptoms with people who were not previously vaccinated and were likely to be more vulnerable to infection by monkeypox. By studying the immune responses of these groups of people, scientists hope to learn whether smallpox vaccine provides effective protection during the course of many years or, possibly, for life.

Another important aspect of this research involves the development of a clearer understanding of the disease characteristics of monkeypox. Scott Wong, Ph.D., assistant scientist at the VGTI who is also working on monkeypox projects, is studying the disease process induced by this virus at the cellular level.

“By gaining a better understanding of the disease process, we can identify weaknesses or vulnerabilities of the disease upon which we can base new vaccines or therapies,’ Wong said.

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