Ponente
Descripción
The four dengue virus serotypes (DENV1-4) are transmitted to humans by mosquitoes of the Aedes genus and cause the disease of the same name. The increment in the incidence of dengue outbreaks and epidemics together with the lack of effective vaccines and antivirals make DENV a threat to human health. Out of the three structural protein of DENV, the envelope (E) protein mediates early events of infection from virus:receptor interaction and membrane fusion and is the main target of the humoral immune response in humans. The functional importance of the structural domain III of the E protein has converted it into a main viral antigen of subunit vaccines against DENV. Here, we used an alanine-scanning library of a recombinant domain III of the E protein of serotype 1 to characterized the IgG response generated during natural infection in terms of relative abundance, serotype-specificity and immunodominant epitopes for the different subclasses. The analysis of 24 human sera of convalescent individuals from 6 days to 1 year after onset of symptoms revealed that IgG1 is the predominant subclass and the one with the highest serotype-specific activity while the response of IgG2 and IgG4 subclasses is largely cross-reactive. Immunodominant regions vary among IgG subclasses in correspondence with their serotype-specificity. IgG3 response against the domain III exhibits less definition in both characteristics, serotype-specificity and immunodominant regions. Results of this work point to critical epitopes to be targeted with subunit vaccines based on the domain III of the E protein of DENV.
