Scientists at La Jolla Institute for Immunology (LJI) are committed to better understanding how the human immune system targets mpox—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 mpox may become endemic in rodents in the United States, making it very difficult to eradicate the disease and prevent future outbreaks. The 2022 mpox 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 mpox virus.
To best protect people, scientists need to know: How effective are the current vaccines—and how durable?
The current vaccines against mpox 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 mpox. 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 mpox 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 mpox. Learn more about the IEDB.
In a recent study, the LJI team, led by by LJI Professor Alessandro Sette, Dr.Biol.Sci. and LJI Research Assistant Professor 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 mpox 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 mpox virus, meaning they could respond to mpox, 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.