Overview

Monkeypox is a viral disease that primarily spreads through skin to skin contact or through exposure to bodily fluids or respiratory secretions from an infected person, according to the World Health Organisation. People with the virus may initially experience flu-like symptoms, including a fever. A few days into the flu-like symptoms, many infected people develop a rash, which can lead to painful pustules on the skin (pox). The illness usually lasts between 6 and 13 days, though some people suffer symptoms for around 21 days. Most patients fully recover. Fatalities are very rare. Learn more about symptoms.

The monkeypox virus is a member of the Orthopoxvirus viral genus. Its relatives include smallpox virus, vaccinia virus, and cowpox virus. Monkeypox is a zoonotic disease, meaning it can spread between humans and animals. The virus was first identified in crab-eating macaque monkeys. The leading theory is that rodents serve as the main animal hosts.

In 2022, global health officials identified multiple outbreak clusters of monkeypox cases in 69 countries that do not normally report monkeypox, including the United States. The virus spread rapidly through summer 2022, leading to 21,272 U.S. cases and 56,026 global cases by the end of August 2022. Learn about communities most at risk.

Monkeypox vaccines are available in the United States, and are recommended for people who have been exposed to the virus and for people who have had sexual partners test positive. According to the CDC, you may also want to get vaccinated “if you are a man who has sex with other men or are a transgender or gender-diverse person who has sex with men and in the past 2 weeks.” More about the vaccines.The therapeutic Tecovirimat (or Tpoxx) has been used as a treatment for monkeypox in the United States and the European Union.

Our Approach

Scientists at La Jolla Institute for Immunology (LJI) are committed to better understanding how the human immune system targets monkeypox—and how vaccines can protect at-risk people. 

One concern is that if the current outbreak is not contained, the virus may spread to more communities, such as children and immunocompromised people. Another concern is that monkeypox may become endemic in rodents in the United States, making it very difficult to eradicate the disease and prevent future outbreaks. The 2022 monkeypox outbreak has also led many to wonder whether an emerging pox virus could cause a serious global pandemic if it proved more transmissible than the current monkeypox virus.

To best protect people, scientists need to know: How effective are the current vaccines—and how durable?

The current vaccines against monkeypox were not actually designed to treat the virus. Dryvax and the similar vaccinia virus vaccine Acambis 2000 were designed to lead the body to mount an immune response against a pox virus called vaccinia virus. Vaccinia virus is similar enough to smallpox (variola virus) that the vaccine proved critical for eradicating smallpox by 1980. When these two vaccines were largely discontinued 20 years ago, they were replaced by a “non-replicating” vaccine called MVA-BN (brand name JYNNEOS), which had a superior safety profile and induced almost equivalent levels of antibodies against variola virus.

Although the vaccines work well against variola virus, little is known about their effectiveness against monkeypox. The data showing vaccine efficacy in humans is limited to one study and on the older Dryvax vaccine. And although the JYNNEOS vaccine is approved to prevent monkeypox infection/disease, no clinical efficacy data is available in humans.

LJI scientists are working to fill these knowledge gaps. One critical tool in this effort is the LJI-run Immune Epitope Database (IEDB). The IEDB gives researchers a way to organize and analyze massive datasets to shed light on exactly how the immune system targets a pathogen such as monkeypox. Learn more about the IEDB.

In a recent study, the LJI team, led by by LJI Professors Alessandro Sette, Dr.Biol.Sci. and Instructor Alba Grifoni, Ph.D., leveraged T cell data in the IEDB to design “peptide pools” and measure how T cells isolated from Dryvax vaccinated people respond to monkeypox sequences. Understanding T cell responses is especially important for protecting patients, as T cells control and terminate pox virus infections.

In September 2022, the researchers reported effective T cell responses in banked samples from Dryvax vaccinated individuals. These T cells also showed cross-reactivity to monkeypox virus, meaning they could respond to monkeypox, even though it wasn’t as familiar to them. The Dryvax vaccine had given the T cells enough information to work with.

The LJI researchers also plan to give scientists worldwide an important look at different vaccination doses and routes, both for antibodies protection and T cell defenses. This is important as it is currently unknown whether the new generation “safer” vaccines are just as effective as the older ones with proven efficacy. This is even more key, because vaccines are currently limiting and different doses and sites of injection are being tried to stretch the vaccine supply further and vaccinate all that are at risk. 

Going forward, LJI scientists plan to study immune responses in newly collected human blood samples from volunteers either infected and recovered, or vaccinated. [You can get involved in this effort. Learn how to volunteer as a study participant.] Researchers here have also made their data, peptide pools, and reagents freely available to support the worldwide effort to stop the virus.