A newly developed therapeutic antibody, capable of neutralizing West Nile virus (WNV) even several days after the onset of infection, may prove an important breakthrough for preventing WNV-related deaths and for tackling other related viruses.

Although birds are the primary carrier of WNV, scientists and doctors have been aware for some time that the mosquitoes that transmit the virus can also pass it along to mammals—including humans. The majority of the population experiences no ill effects from WNV exposure, but those who do are at risk for encephalitis and meningitis, both severe and potentially fatal afflictions of the brain. Patients older than 50 years of age are at particular risk.

At present, there is no human vaccine available for WNV, although research has shown that the body can mount a successful immune response with antibodies that neutralize viral infection. In an effort to explore the potential of monoclonal antibodies as anti-WNV therapeutics, Michael Diamond of the Washington University School of Medicine (St. Louis, MO) and his colleagues immunized mice with recombinant viral envelope protein, which is generally known to be a primary target for immune recognition. They generated nearly 50 different monoclonal lines, a dozen of which proved capable of neutralizing WNV more effectively than human polyclonal antisera (Nat. Med., May).

One of the most effective antibodies, E16, was capable of blocking infection of several different mouse and human cell lines by several different WNV strains; at the same time, the antibody was specific enough not to neutralize closely related, non-WNV viruses. The antibody proved equally effective in mice; for mice that had been injected 2 days after infection with E16, the survival rate rose from 10% to >90%. E16 even offered protection when injected several days later, when infection had progressed to the central nervous system. Increased doses of E16 given 5 days after infection still conferred 90% survival rates, and 9 days later all virus had been cleared from the brains of 68% of the treated mice.

Diamond's team has also developed a 'humanized' version of E16, which is equally effective in mice but may prove more effective for human patients. “Our results are the first successful demonstration of a humanized monoclonal antibody as postexposure therapy against a viral disease,” the authors write, “and suggest that antibody-based therapeutics may have more broad utility than previously appreciated.”