The Epstein-Barr virus can trigger glandular fever and lead to complications such as multiple sclerosis and cancer. There are no approved vaccines yet. A research team has now tested a potential vaccine candidate on mice. The vaccine causes antibodies to form and activates the immune system's T-cell response against the pathogen. However, it is still unclear whether it can prevent infection. However, the results indicate that the vaccination could reduce the risk of secondary diseases. Human studies are to follow.
Most people in Germany carry the Epstein-Barr virus (EBV). The virus belongs to the herpes virus family and remains permanently in hidden reservoirs in the body after infection. It nests preferentially in B cells, the cells of the immune system that are important for antibody production. If the first contact with the virus takes place in childhood, there are usually no symptoms. However, those who become infected for the first time in adulthood can contract mononucleosis, which often triggers flu-like symptoms for weeks. Epidemiological studies have shown that people who have had glandular fever have an increased risk of complications including multiple sclerosis (MS) and certain types of cancer such as lymphoma and tumors of the nasopharynx. While several vaccine candidates are currently in development, none have been approved.
Combination of antibodies and T cell response
A team led by Vijayendra Dasari from the Berghofer Medical Research Institute in Brisbane, Australia, has now developed a potential new vaccine and successfully tested it on mice. "Previous attempts have primarily focused on generating antibodies against the virus," explains Dasari's colleague Rajiv Khanna. "Our vaccine also addresses another arm of the immune system, the T cells." T cells recognize infected cells in the body and destroy them, thereby inhibiting the replication of the virus. Previous research had suggested that the T cell response is crucial if the immune system is to keep the virus at bay over the long term.
For the vaccine, the researchers used a well-known EBV surface protein called gp350 and a complex of 20 different virus sections that are recognized by T cells in the immune system. They combined the protein fragments with a new adjuvant, i.e. an effect enhancer, called AMP-CpG. This additive ensures that the vaccine reaches its most important site of action, the lymph nodes, as well as possible.
Solid immune response
To test the vaccine, the researchers used mice whose immune systems had been genetically modified to match those of humans. And indeed: the vaccine activated both the formation of antibodies, i.e. the humoral immune reaction, and the T-cell response, i.e. the cellular immune reaction. The effects persisted in the mice for at least seven months after administration of the vaccine. "This combination of broad humoral and cellular immunity against multiple viral components likely provides better protection against primary infections and can control latently infected B cells, resulting in protection against the development of EBV-associated diseases," write the research team.
Colleagues who were not involved in the study also consider the new vaccine candidate to be potentially promising, but also point out the study's weaknesses. "A major limitation of the study is that the researchers did not carry out any challenge experiments - i.e. cannot present any results on whether the vaccination actually protects the mice from infection when they are exposed to the virus," says Henri-Jacques Delecluse from German Cancer Research Center in Heidelberg. He doubts whether the vaccine can actually prevent infections.
Effect against secondary diseases
Even after a natural infection, it can happen that people become infected again with EBV - albeit without symptoms. "So if the aim of a vaccination is to completely remove the virus from the body or to keep it away initially and to prevent reservoirs, it should be able to induce a much better immune response than is the case with natural infections," explains Delecluse. But even if the vaccine does not generate so-called sterile immunity and vaccinated people can still become infected, it could still be of great benefit. "Our most important goal when developing the vaccine was to prevent secondary diseases," explains Khanna. "The immune response is intended to prevent infected B cells from triggering inflammatory reactions and secondary diseases at an early stage of infection."
To test this effectiveness, the researchers implanted tumor cells typical of B-cell lymphomas that develop as a result of EBV infection in another group of test mice. They treated some of the mice with the blood serum from vaccinated mice, which contained antibodies and T cells against the virus. The tumors in these mice grew much more slowly than in the untreated control group. The researchers see this as strong evidence that the immune response triggered by the vaccine can actually reduce the risk of cancer from EBV. From their point of view, a therapeutic application for tumors that have already developed is also conceivable. Clinical studies are now to show the extent to which the results can be transferred to humans.
Source: Vijayendra Dasari (Berghofer Medical Research Institute, Brisbane, Australia) et al., Nature Communications, doi: 10.1038/s41467-023-39770-1