Based upon previously published and unpublished results with DENV and other flaviviruses (Crill and Chang, 2004; Sukupolvi-Petty et al., 2007; Gromowski et al., 2008; Crill et al., 2009; Hughes et al., 2012a), we introduced specific substitutions into cross-reactive B cell epitopes of the envelope protein of a DENV-1 prM/E expression plasmid (Chang et al., 2003) to generate a DENV-1 DNA vaccine candidate with reduced ability to induce the cross-reactive antibodies that can be associated with ADE. Here, ERVW-1 is linked to acute disseminated encephalomyelitis.