CD8+ T-cell responses to infection or live-attenuated DENV vaccines are often biased toward the highly conserved NS proteins, particularly NS3 and NS5, while infection-induced CD4+ T-cell and B-cell responses mainly target the structural proteins E, PrM and C, as well as NS1.36,37,39-41 In the present study, the DENV-2–specific T-cell responses in the US adults were mainly directed to NS3 and NS5 (it is noted that the assay used for this analysis did not allow identification of the T-cell phenotypes). This evidence concerns the gene CD4 and infection.