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Tick-borne encephalitis is a disease that is just as bad as it sounds. Once bitten by an infected tick, some people develop flu-like symptoms that quietly resolve but leave behind widespread neurological disorders – brain swelling, memory loss, and cognitive decline. Cases are increasing in Central Europe and Russia. Around 10,000 incidents are reported each year. Vaccines can provide protection, but only for a limited time. There is no cure.

Now, a new study describes antibodies that can neutralize the virus transmitted by tick bites. These so-called largely neutralizing antibodies have shown promise in preventing TBE in mice and could advance the development of better vaccines for humans. In addition, preliminary results suggest that the antibodies not only prevent tick-borne encephalitis, but can even treat the disease, as well as the related Powassan virus that occurs in the United States.

Lead author Marianna Agudelo and colleagues in Rockefeller’s Michel C. Nussenzweig laboratory examined nearly 800 antibodies from people who had recovered from TBE or had been vaccinated to prevent infection. The most effective antibodies, labeled VH3-48, were found to be the best at warding off future infections. They found that VH3-48 neutralized laboratory-grown strains of the TBE virus as well as other tick-borne diseases, including Langat, Louping’s disease, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan virus.

The researchers also showed that these strong antibodies are not common; In fact, most of the antibodies produced by people exposed to the TBE virus are of poor quality, with the coveted VH3-48 antibodies occurring only occasionally. In addition, vaccinated patients in the study failed at all to develop VH3-48 antibodies. “You would expect the most widely used antibodies to be the absolute best, but we didn’t find that with TBE,” says Agudelo. “This could explain how the virus tricked the immune system into making poor quality antibodies.”

The discovery of VH3-48 gives hope for a more effective TBE vaccine. Current vaccines require three doses two years apart and only provide about five years of protection before a booster shot is needed. Next-generation vaccines, designed to persuade the body to produce the rare antibody VH3-48, could be more effective, require fewer booster vaccinations, and also protect against a range of tick-borne viruses.

“Such a vaccine would not only be more elegant, but also better focused,” says Michel C. Nussenzweig, Professor of Zanvil A. Cohn and Ralph M. Steinman and Head of the Laboratory for Molecular Immunology at Rockefeller. “Now that we have the structures for these antibodies, we know what to aim for in order to develop more effective vaccines.”

Largely neutralizing antibodies can also be the first specific treatment for TBE. Nussenzweig, Agudelo and colleagues found that mice infected with TBE recover after antibody therapy, although it remains to be seen whether this finding can be transferred to humans.

“The next step is a clinical study of the antibodies,” says Nussenzweig, “maybe in Europe, where there are many cases, to see if we can relieve the symptoms of people with encephalitis.”

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More information:
Marianna Agudelo et al., Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease, Journal of Experimental Medicine (2021). DOI: 10.1084 / jem.20210236 Provided by Rockefeller University

Quote: Brain diseases transmitted by tick bites can be treated (2021, April 9) and accessed on April 9, 2021 at

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