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

Abstract

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-γ 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

Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study—The COViNEPH Project

“…Because the recombinant protein vaccines use only a protein fragment of receptor binding domain as the antigen, they may have lower immunogenicity than the whole-pathogen vaccine candidates containing more than 20 immunoreactive epitopes [21,22]. In a randomized phase 1/2 clinical trial with Valneva, antigen-specific interferon-γ T-cells reactive were observed against the spike, membrane, and nucleocapsid proteins [21]. Of course, take into account the fact that not all viral epitopes of the virus need to be immunogenic [23].…”

Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults

“…After virus propagation, β-propiolactone is used for viral inactivation in order to preserve the native surface structure of the virion, in a robust process that yields high-density and intact Spike protein. 6 Additionally, VLA2001 is adjuvanted with cytosine phospho-guanine (CpG) 1018 and aluminum hydroxide.…”

An overview on inactivated and live‐attenuated SARS‐CoV‐2 vaccines

“…The vaccine was exhibited to be safe and well-tolerated and produced both humoral and cellular immune responses, with a clear dose-dependent effect. 34 All samples showed neutralized antibodies against the ancestral virus. The incidence of neutralizing antibodies against Omicron was 87%.…”

“…The most frequent local reactions were tenderness (58.2%) and pain (41.8%), and systemic reactions included headache (46%) and fatigue (39.2%). The vaccine was exhibited to be safe and well‐tolerated and produced both humoral and cellular immune responses, with a clear dose‐dependent effect 34 . Later, Valneva participated in the Cov‐Boost clinical trial (ISRCTN73765130) to examine seven different COVID‐19 booster vaccines.…”

“…The vaccine was exhibited to be safe and well‐tolerated and produced both humoral and cellular immune responses, with a clear dose‐dependent effect. 34 Later, Valneva participated in the Cov‐Boost clinical trial (ISRCTN73765130) to examine seven different COVID‐19 booster vaccines. The results of this trial revealed that all studied vaccines, including VAL2001, boosted antibody and neutralizing responses after ChAd/ChAd or BNT/BNT initial course, with no safety concerns.…”