The envelope (E) protein is composed of three domains (ED1, ED2 and ED3) with ED3 targeted by the most potent neutralizing antibodies. DENV-2 strains can be divided into six genotypes. Comparison of ED3 of representative strains of the six genotypes revealed that there are nine variable residues that are specific to a given genotype. Recombinant ED3s (rED3s) of six different DENV-2 strains representing all nine variable residues were expressed, and their reactivity against a panel of two DENV-2 type-specific and three DENV complex-reactive monoclonal antibodies (mAbs) were compared. The differences in binding affinity to the rED3s representing different DENV-2 genotypes were relatively small, with the exception of type-specific-mAb 3H5 that showed up to 10-fold differences in binding between genotypes. Overall the binding differences did not lead to detectable differences in neutralization. Based on these results, DENV-2 ED3-specific neutralizing antibodies will likely be effective against DENV-2 strains from all six genotypes.
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