Researchers have identified 'broadly neutralizing' antibodies that protect against infection by multiple, distantly related alphaviruses—including Chikungunya virus (above)—that cause fever and debilitating joint pain. Shown is a cryoelectron microscopy reconstruction of the Chikungunya virus.[Wikimedia user A2-33]
Researchers have identified ‘broadly neutralizing’ antibodies that protect against infection by multiple, distantly related alphaviruses—including Chikungunya virus (above)—that cause fever and debilitating joint pain. Shown is a cryoelectron microscopy reconstruction of the Chikungunya virus.[Wikimedia user A2-33]

For years, scientists have been on the hunt to develop vaccines that would protect against all or most strains of particularly virulent viruses such as influenza. Yet, imagine if it were possible to generate a vaccine that would be protective for an entire class of viruses. The theory may have just taken a big step closer to reality.

A new study by researchers at the Washington University School of Medicine in St. Louis (WUSTL) has identified broadly neutralizing antibodies that protect against infection in mice from multiple, distantly related alphaviruses—including Chikungunya virus (CHIKV)—that cause fever and debilitating joint pain. The results of this study could have wide implications toward the development of antibody treatment for a vast array of alphaviruses.    

“There is a lot of emphasis on identifying and understanding broadly neutralizing antibodies for other viruses—HIV, hepatitis C virus, dengue virus, influenza virus—but most of those antibodies neutralize different strains of the same virus,” explained senior author Michael Diamond, M.D., Ph.D., a professor of medicine and director of the Division of Infectious Diseases and Vaccine Development in the Center for Human Immunology and Immunotherapy Programs at WUSTL. “What we've identified here are antibodies that actually neutralize several different alphaviruses.”

The findings from this study were published online recently in Cell through an article entitled “Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress.”

The WUSTL investigators were interested in studying arthritogenic alphaviruses—those that cause characteristic symptoms of fever followed by arthritis-like joint pain. These viruses are all spread to their hosts through mosquito vectors and typically cause sporadic outbreaks, although Chikungunya has begun to spread more globally leading to more persistent epidemics.

For example, over the past several years CHIKV has caused millions of infections annually across the globe and so far in 2015, there have been 650 cases seen in U.S. residents, largely among travelers returning from the Caribbean, where they were infected. Currently, there is no vaccine or treatment for CHIKV or other alphaviruses. 

In the current study, the researchers screened 60 neutralizing mouse and human antibodies against CHIKV and determined that 10 reacted against three or more different alphaviruses that cause arthritis-like symptoms. They also identified an epitope of the alphavirus that is identical across the entire arthritogenic alphavirus family.

Using in vitro cell culture studies, Dr. Diamond and his team observed that antibodies which recognized the alphavirus epitope also protected against infection by multiple alphaviruses. The antibodies blocked multiple steps in the viral life cycle, including the virus's ability to enter or exit host cells.

Furthermore, to confirm that the antibodies could protect animals from disease, the researchers infected mice with three different alphaviruses: Chikungunya, the closely related O'nyong'nyong virus, or the more distantly related Mayaro virus. Employing the two most potent broadly neutralizing antibodies, the researchers treated the infected mice and saw markedly reduced joint disease caused by any of the viruses.

“If you can make an antibody response against this region, you may be able to protect against many viruses in the family,” noted Dr. Diamond. “Our group is making proteins now that focus on this epitope, and we're planning to start immunizing animals soon to see if we generate the right kinds of antibodies.”

Typically, individuals who are infected with alphaviruses produce antibodies against many viral epitopes, some of which are not protective—setting up a weak immune response scenario that allows the virus time to replicate and exert its pathogenic effects. Conversely, people who are immunized with proteins expressing the key epitope identified by the WUSTL researchers should be able to rapidly produce proper protective antibodies, thereby short-circuiting the disease process.

“We have more work to do but are encouraged that targeting this epitope could be a viable strategy for developing vaccines or treatments against Chikungunya and other related viruses that cause significant disease worldwide,” Dr. Diamond concluded.








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