Dengue Virus 1/3 Chimeras Genome sequencing

The envelope glycoprotein (E) is the primary target of serotype-specific (TS) neutralizing antibodies (nAbs) after dengue virus infection (DENV1-4). To identify the primary DENV3 nAB targets in sera, chimeric DENV1 recombinant viruses were recovered, encoding the DENV3 E domains (EDs) I, II or III. Using chimeric viruses, we demonstrate that DENV3 EDII is the principal target of TS polyclonal nAb responses after natural infection and presents multiple neutralizing monoclonal antibody epitopes. In contrast to convalescent sera, individuals vaccinated with a DENV3 monovalent vaccine elicited serum TS nAbs that targeted each ED in a patient-dependent fashion, with an emphasis on EDI and EDIII. Responses were sensitive to DENV3 genotypic variation. The DENV1/3 panel identifies key structural interactions for prM/E virion infectivity, provides novel reagents to measure serum ED TS nAbs, and reveals fundamental differences in TS nAb immunity after natural infection or vaccination, which may prove relevant to protective immunity.