Abstract Adenoviral vectors can induce T and B cell immune responses to Ags encoded in the recombinant vector. The MHC class II invariant chain (Ii) has been used as an adjuvant to enhance T cell responses to tethered Ag encoded in adenoviral vectors. In this study, we modified the Ii adjuvant by insertion of a furin recognition site (Ii-fur) to obtain a secreted version of the Ii. To test the capacity of this adjuvant to enhance immune responses, we recombined vectors to encode Plasmodium falciparum virulence factors: two cysteine-rich interdomain regions (CIDR) α1 (IT4var19 and PFCLINvar30 var genes), expressed as a dimeric Ag. These domains are members of a highly polymorphic protein family involved in the vascular sequestration and immune evasion of parasites in malaria. The Ii-fur molecule directed secretion of both Ags in African green monkey cells and functioned as an adjuvant for MHC class I and II presentation in T cell hybridomas. In mice, the Ii-fur adjuvant induced a similar T cell response, as previously demonstrated with Ii, accelerated and enhanced the specific Ab response against both CIDR Ags, with an increased binding capacity to the cognate endothelial protein C receptor, and enhanced the breadth of the response toward different CIDRs. We also demonstrate that the endosomal sorting signal, secretion, and the C-terminal part of Ii were needed for the full adjuvant effect for Ab responses. We conclude that engineered secretion of Ii adjuvant–tethered Ags establishes a single adjuvant and delivery vehicle platform for potent T and B cell–dependent immunity.