Immunogenicity and safety of inactivated whole virion Coronavirus vaccine with CpG (VLA2001) in healthy adults aged 18 to 55: a randomised phase 1 /2 clinical trial

Background We assessed the safety, tolerability and immunogenicity of VLA2001 is a whole-virion inactivated SARS-CoV-2 vaccine adsorbed to alum with a toll-like receptor 9 agonist adjuvant in healthy volunteers aged 18-55. Methods The first 15 participants were enrolled, in groups of 5, to receive two doses, separated by 21 days, of one of three dose concentrations, administered intramuscularly. 138 further participants were randomised 1:1:1 to receive the same 3 dose concentrations, in a double blinded manner. Primary outcomes were solicited adverse reactions 7 days after each vaccination and neutralising antibody geometric mean titres (GMT) against SARS-CoV-2, 2 weeks after the second vaccination (day 36), measured by live microneutralisation assay against wild-type virus (MNA50). Secondary outcomes included unsolicited adverse events, and humoral and cellular responses at day 36, measured by IgG ELISA against Spike protein and interferon-gamma secreting T-cells by ELISpot stimulated with multiple SARS-CoV-2 antigens. (ClinicalTrials.gov NCT04671017, ISRCTN 82411169) Findings Between December 16, 2020 and January 21, 2021, 153 participants were enrolled and randomised evenly between the dose groups. The rates of solicited reactions were similar after the first and second doses and between the three dose groups. The most frequent local reactions were tenderness (58.2%) and pain (41.8%) and systemic reactions were headache (46%) and fatigue (39.2%). In the high dose group, two weeks following the second dose, the geometric mean titres were 530.4 (95% CI: 421.49, 667.52) for neutralizing antibodies and 2147.9 (95% CI: 1705.98, 2704.22) for S-binding antibodies. There was a dose dependent response with 90.0% (95% CI:78.0%.,97.0%) seroconversion (4-fold rise) at day 36 in the high dose group, which was significantly higher than rates in both the medium (73.5%; 95% CI: 59%,85%), CIs) and low dose (51%; 95%CI: 37%,65%) rate, CIs) groups (both p < 0.001). Antigen-specific interferon-{gamma} T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49% of high dose recipients, respectively. Interpretation VLA2001-201 was well tolerated and produced both humoral and cellular immune responses, with a clear dose-response effect