Aim: Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features promoting strong CD8+ T-cell responses. Materials & methods: Three different self-adjuvanting lipid core peptide nanovaccines each comprising four copies of the dominant ovalbumin CD8+ T-cell epitope and varying in the utilization of a polylysine or glucose core with 2-amino-hexadecanoic acid (C16) or 2-amino-dodecanoic acid (C12) lipids were synthesized. Vaccines were tested for ability to induce CD8+ T-cell responses and inhibit tumor growth in vivo. Results: The construct utilizing C12 lipids and polylysine core induced very robust effector T cells shown to have in vivo effector capability as demonstrated by in vivo cytotoxicity and ability to inhibit tumor growth as well as modulation of dendritic cell activation. Conclusion: The C12 polylysine platform was an effective configuration for induction of potent CD8+ T-cell responses.