Smallpox Vaccine May Help Fight Monkeypox Outbreak

There is growing evidence that a vaccine developed to combat smallpox may also be effective against the monkeypox virus, according to a new study by researchers at the La Jolla Institute for Immunology. The study, published in Cell Host & Microbe, is the first to provide evidence that the JYNNEOS vaccine, also known as MVA-BN, could train the body's virus-fighting T cells to recognize monkeypox sequences.

The study comes at a time when more than 100 countries have reported unprecedented monkeypox outbreaks. In the United States alone, over 28,000 reported cases and 11 deaths have been attributed to the virus since May 2022.

The monkeypox virus is a member of the orthopox family of viruses, which includes the variola virus that causes smallpox. Smallpox was eradicated worldwide in 1980 thanks to a successful vaccination campaign using the Dryvax vaccine, which was based on a similar non-live attenuated orthopox virus called modified vaccine ankara (MVA).

The JYNNEOS vaccine, based on a similar MVA, is already approved to prevent monkeypox infection and severe disease. However, researchers do not yet have clinical efficacy data from human trials. Despite this, it is known that the monkeypox virus is similar enough to other orthopoxviruses that immunization against vaccinia, another orthopoxvirus, can also train the immune system to fight monkeypox.

For their work, the researchers used information about a related virus, vaccinia, to predict which parts of the monkeypox virus would be recognized by the immune system. They then tested this prediction by creating pools of peptides and using them to detect immune responses in a group of people vaccinated against the related virus. This allowed the researchers to identify the parts of the monkeypox virus that are most important for triggering an immune response, as well as help them understand how the body fights the virus and how well vaccines against it work.

"This study gives us confidence that T cell response induced by the JYNNEOS vaccine should be able to also recognize monkeypox virus," says LJI Professor Alessandro Sette, who co-led the study.

The Dryvax vaccine was effective because it had many immune system targets in common with the variola virus. This meant that training the body to recognize the vaccine also taught immune cells to recognize the variola virus. However, the Dryvax vaccine had harmful side effects, especially in immunocompromised people.

JYNNEOS was designed to have a better safety profile, but because smallpox was eradicated, scientists couldn't see how the vaccine performed in human patients in real-world infection scenarios. The new study from the La Jolla Institute shows that the known targets of T cell responses seen in the VACV proven-efficacy vaccine are also found in JYNNEOS and monkeypox, suggesting that the JYNNEOS vaccine can trigger an effective T cell response against monkeypox infection.

"Vaccines such as JYNNEOS should be able to induce T cells that also recognize monkeypox and can provide protection from severe disease," explains co-author Alba Grifoni, an instructor at LJI.