Recombinant glycoprotein-deficient lymphocytic choriomeningitis virus-based vaccine vectors (rLCMV/ΔGP) are potent CD8+T cell inducers. To investigate the underlying molecular requirements, we generated a nucleoprotein-deficient vector counterpart (rLCMV/ΔNP). NP but not GP is a minimaltrans-acting factor for viral transcription and genome replication. We found that, unlike rLCMV/ΔGP, rLCMV/ΔNP failed to elicit detectable CD8+T cell responses unless NP wastranscomplemented in a transgenic host. Hence, NP-dependent intracellular gene expression is essential for LCMV vector immunogenicity.