Functional properties of DENV EDIII-reactive antibodies in human DENV-1-infected sera and rabbit antiserum to EDIII

The envelope domain III (EDIII) of the dengue virus (DENV) has been confirmed to be involved in receptor binding. It is the target of specific neutralizing antibodies, and is considered to be a promising subunit dengue vaccine candidate. However, several recent studies have shown that anti-EDIII antibodies contribute little to the neutralizing or enhancing ability of human DENV-infected serum. The present study involved an analysis of the neutralization and antibody-dependent enhancement (ADE) activities of EDIII-reactive antibodies in human convalescent sera from patients with primary DENV-1 infection and rabbit antiserum immunized with recombinant DENV-1 EDIII protein. The results indicated that serum neutralization was not associated with titres of EDIII-binding antibodies in the human DENV-1-infected sera. The depletion of anti-EDIII antibodies from these serum samples revealed that the anti-EDIII antibodies of the patients contributed little to neutralization and ADE. However, the EDIII-reactive antibodies from the rabbit antiserum exhibited protective abilities of neutralization at a high dilution (similar to 1: 50,000) and ADE at a low dilution (similar to 1: 5,000) for the homotypic DENV infection. Notably, the rabbit antiserum displayed ADE activity only at a dilution of 1: 40 for the heterotypic virus infection, which suggests that EDIII-reactive antibodies may be safe in secondary infection with heterotypic viruses. These results suggest that DENV EDIII is not the predominant antigen of the DENV infection process; however, purified or recombinant DENV EDIII may be used as a subunit vaccine to provoke an effective and safe antibody response.