Lentiviral vectors (LVs) are promising delivery systems for gene therapy, and they can be further engineered to increase their potential for effectively delivering transgenes to desired cell populations. Here, we have engineered LVs pseudotyped with envelope glycoproteins derived from lymphocytic choriomeningitis virus (LCMV) for antigen delivery to elicit vaccine-directed immune responses. Two variants, LCMV-WE and LCMV-Arm53b, were evaluated for their ability to mediate LV-based cellular transduction in vitro. LCMV-WE with a leucine residue at position 260 (260L) is known for its high-affinity binding with a cellular receptor, α-dystroglycan (α-DG), whereas LCMV-Arm53b has low-affinity binding resulting from a phenylalanine residue at the same position. In contrast to LCMV-Arm53b, we found that LVs pseudotyped with LCMV-WE could transduce 293T cells and murine dendritic cells much more efficiently based, at least in part, on their favorable interaction with α-DG. In mice, LCMV-WE-bearing LVs encoding a model antigen, invariant chain ovalbumin, could elicit substantial antigen-specific CD8(+) T cell immune response. The response could be further enhanced by a homologous boosting immunization with the same vector. These findings offer evidence to support the potential utilization of LCMV-WE-bearing LVs for vectored vaccines against cancer and infectious diseases.