Booster Dose Study to Assess the Safety and Immunogenicity of ACM-001 Administered Intramuscularly or Intranasally.

* Open label, randomized, single dose study. * The ACM-001 vaccine will be evaluated in a single ascending dose (administered IM in 4 groups of 5 subjects and IN in 4 groups of 5 subjects), which will explore the amount of SARS-CoV-2 spike protein derived from strain B.1.351 (5 µg and 15 µg) and adjuvant CpG7909 (25 µg and 125 µg) required to provide the optimum immunogenicity and safety, as a booster dose in subjects who were previously vaccinated (two, three or four doses) against SARS-CoV-2. * Fourty (N=40) healthy adult volunteers aged 18-55 years, will be enrolled and randomized in the IN or IM cohorts if they meet eligibility criteria at baseline. Participants who benefited from a complete 2 dose-primary vaccination with or without one or two booster dose with registered and commercial COVID-19 vaccine(s), at least 3 months prior to study vaccination (maximum 5,000 BAU/mL of anti-S Ig), with or without previous infection by COVID-19 can be enrolled in this study. * Participants of cohorts 1,3,5 and 7 will receive an IM injection into the deltoid region, consisting of 0.4 mL per dose on Day 1. In cohorts 2, 4, 6 and 8, the vaccine will be administered IN (2 x 0.2 mL per dose) on Day 1. * Participants will be observed closely in the research unit for at least 2 hours following vaccination. * As from Day 30 (following completion of Day 29 visit), subjects may receive an additional (3rd or 4th or 5th) commercial SARS-CoV-2 vaccine dose. * All subjects (having received or not a commercial dose of a SARS-CoV-2 vaccine at any point of time during their study participation) will be followed up for safety and immunogenicity on Day 85 and Day 180 visits. * Solicited local and systemic AEs will be collected for 7 days following the vaccination using a daily reactogenicity electronic diary (eDiary). Non-serious unsolicited AEs will be collected from administration until 28 days following vaccination. Serious AEs (SAEs) and AEs of special interest (AESI; list determined by the Safety Platform for Emergency Vaccines (SPEAC; Brighton collaboration)) will be collected throughout the whole 6-month study period. * Sentinel dosing will be applied to all cohorts for the early detection of safety signals. Two subjects will be dosed ahead of the other volunteers (at least 48 hours), with an interval of at least 2 hours between them, to ensure there are no serious acute reactions following vaccination. After global evaluation by the Investigator (or the responsible physician) and phone contact with the subjects on Day 3, and providing there are no safety concerns, the rest of the cohort (N=3) will be dosed. * Seven-day safety data of all subjects (N=10) of a given Ag/CpG dose level will be reviewed by an independent data safety monitoring board (DSMB). The interval between the last subject receiving his/her vaccine and vaccination of three sentinel subjects with the ascending dose levels will be at least 10 days. * On Day 1 (pre-vaccination) and on Days 8 and 29 (28 days post-vaccination), blood samples will be drawn for analysis of safety parameters. * At all timepoints, serum and saliva samples will be collected for analysis of the humoral immune responses (IgG, IgA and neutralizing antibodies). * The duration of the study for each subject will be approximately 6 months.