The Human Antibody Response Against WNV

Throsby, Mark; Goudsmit, Jaap; Kruif, John de

Experimental evidence has shown that antibody responses to West Nile virus (WNV) are critical for protection from WNV-mediated disease. Antibody responses are also an important immune correlate of protection for the clinical evaluation of WNV vaccines. However, little direct study has been carried out on the characteristics of the human antibody response to natural WNV infection. Preliminary evidence suggests that there are important differences in the way humans and experimental animals mount humoral responses to WNV. In humans, IgM is remarkably persistent in the serum and specific IgG is slow to appear. In addition, mapping of the IgG response to the functionally relevant E-protein suggests that it directed away from critical protective epitopes and towards weakly neutralizing immunodominant epitopes. These findings have important implications for vaccine design and testing.