New vaccines with broader protection against SARS-CoV-2 are needed to reduce the risk of immune escape and provide broad and long-lasting cellular immunity. The objectives of the naNO-COVID trial were to evaluate the safety and immunogenicity of a CD8 + T cell, gold nanoparticle-based, peptide COVID-19 vaccine. A randomized, double-blind, vehicle-controlled, phase 1 trial in healthy adults to receive PepGNP-Covid19 or Vehicle-GNP, followed over 180 days, using a dose-escalation strategy. Twenty participants received PepGNP-Covid19 (low dose [LD] or high dose [HD], n = 10 each) and six Vehicle-GNP (LD or HD, n = 3 each). Vaccinations were safe. No serious adverse events were reported. Most of the adverse events were mild, two adverse events of special interest related to the product (fever and fatigue). Reactogenicity was similar overall between vaccine, comparator, and doses. Virus-specific humoral responses in LD PepGNP-Covid19 and Vehicle-GNP groups coincided with SARS-CoV-2 infections. PepGNP-Covid19 vaccination induced the modulation of Covid19-specific CD137 + CD69 + CD8 + , and an increase at day 35 particularly in central and effector memory T cells in LD group, and in late effector memory cells in HD group. The favourable safety profile and cellular responses observed support further development of PepGNP-Covid19. ClinicalTrials.gov, NCT05113862, approved 09.11.2021.