The findings, published in the journal Cell, indicate that the antibodies were effective against all alphaviruses tested, implying that they could serve as the basis for therapies or as a template for a universal vaccine.
Alphaviruses are a group of about 30 species divided into two branches. Historically, viruses such as chikungunya, Mayaro, O’nyong-nyong, and Ross River, which all cause fever, rash, and arthritis, were restricted to Africa, Asia, and Europe.
Chikungunya, however, began spreading throughout the Caribbean and areas of North and South America in 2013.
The other subgroup of alphaviruses is located in the Americas and is comprised of Eastern, Western, and Venezuelan equine encephalitis viruses. These viruses cause brain diseases.
The team previously found a class of antibodies that neutralises a large number of members of the alphavirus group that cause arthritis. However, such antibodies were ineffective against all viruses.
To find potential antibodies, they evaluated a collection of antibodies produced by two patients infected with chikungunya virus. They evaluated the antibodies against a panel of alphaviruses representing both subgroups. Two antibodies were capable of recognising all alphaviruses tested.
They then tested if the antibodies could protect mice from developing arthritis or brain illness. They tested each antibody against two alphaviruses that cause rheumatoid arthritis and three alphaviruses that cause brain infections using mice. Both antibodies provided protection against all viruses.
Additional investigations demonstrated that the antibodies worked by preventing virus particles in development from exiting one cell and infecting another. Antibodies bind to a segment of the viral protein E1 that is exposed exclusively during the leaving process. Once the virus has fully grown and separated from the host cell, the E1 protein is folded into and buried within the virus particle.
In a related paper published in the same issue of Cell, James E. Crowe, MD, of Vanderbilt University Medical Center reports that antibodies directed against the E1 protein bind to a wide variety of alphaviruses, prevent them from exiting cells, and protect animals against rheumatoid arthritis and brain infections. Crowe and current study authors have worked together for a lengthy period of time and each contributed to the other’s paper.
“If we could figure out how to make a vaccine that targets the E1 protein effectively, it would be a cost-effective way to provide broad protection for people in resource-limited places, which is where most alphavirus infections occur,” said the study author.
“It’s challenging to make such a vaccine since the target is hidden most of the time. But there are techniques that can be used to make the immune system focus on E1 and generate a good antibody response against it. That’s the next step toward creating a universal vaccine.”
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