Integrase defective lentiviral vector as a vaccine platform for delivering HIV-1 antigens

Despite improvements in the therapy of HIV infection allow for controlling AIDS pandemic spread, to date no effective preventive HIV‐1 vaccine is available. To be effective, a global HIV‐vaccine will have to elicit potent and durable immune responses against the enormous diversity of HIV variants. Vaccine delivery systems play a pivotal role for a successful vaccine. In this context, self-inactivating, non-replicating and non-integrating IDLVs (Integrase Defective Lentiviral Vectors) represent attractive tools for gene delivery into target cells with high efficiency, inducing both humoral and cellular immune response in mice and NHP animal models. Here we describe the development of IDLV for the delivery of two novel rationally designed HIV-1 antigens: HTI (HIVACAT T‐cell Immunogen), a mosaic antigen containing conserved regions in the gag, pol, vif and nef genes and including beneficial epitopes, targeted by functional T-cells in patients with low viral load; and UFO (Uncleaved pre‐Fusion Optimized gp140 Trimers ), a consensus sequence of Env from HIV group M, modified to increase native-like trimer production and exposure of bNAbs epitopes. In particular, HIV- or SIV-based IDLV-HTI were able to induce specific cell-mediated immune response in BALB/c mice. Moreover, SIV-based IDLV expressing UFO antigens induced high titres of specific Abs in BALB/c mice and tier 1 NAbs in NHP.