Dominant epitopes of cross‐reactive anti‐domain III human antibody response change from early to late convalescence of infection with dengue virus

Abstract

AbstractCross‐neutralizing activity of human antibody response against Dengue virus complex (DENV) changes importantly over time. Domain III (DIII) of the envelope protein of DENV elicits a potently neutralizing and mostly type‐specific IgG response. We used sera from 24 individuals from early‐ or late convalescence of DENV1 infection to investigate the evolution of anti‐DIII human IgG with the time lapse since the infection. We evaluated the correlation between the serotype‐specific reactivity against recombinant DIII proteins and the neutralization capacity against the four serotypes, and examined its behavior with the time of convalescence. Also, we use a library of 71 alanine mutants of surface‐exposed amino acid residues to investigate the dominant epitopes. In early convalescence anti‐DIII titers and potency of virus neutralization were positively associated with correlation coefficients from 0.82 to 1.0 for the four serotypes. For late convalescence, a positive correlation (r = 0.69) was found only for DENV1. The dominant epitope of the type‐specific response is centered in the FG‐loop (G383, E384, and K385) and includes most of the lateral ridge. The dominant epitope of the anti‐DIII cross‐reactive IgG in secondary infections shifts from the A‐strand during early convalescence to a site centered in residues E314‐H317 of the AB‐loop and I352‐E368 of the DI/DIII interface, in late convalescence. An immunoassay based on the detection of IgG anti‐DIII response can be implemented for detection of infecting serotype in diagnosis of DENV infection, either primary or secondary. Human dominant epitopes of the cross‐reactive circulating antibodies change with time of convalescence.