EFFECTS OF HOMOLOGOUS AND HETEROLOGOUS BOOSTER VACCINATIONS OF THE INACTIVATED DUAL-ADJUVANTED VACCINE VLA2001 AGAINST COVID-19 INCLUDING VARIANTS OF CONCERN: A PHASE 3 RANDOMIZED CLINICAL TRIAL

VLA2001 is a highly-purified, inactivated whole-virus SARS-CoV-2 vaccine based on a dual-adjuvant system of Alum and CpG1018 for induction of a robust immune response. The vaccine was designed using a well-established technology platform and has received full marketing authorization in Europe. In a pivotal Phase 3 trial, VLA2001 demonstrated superior neutralizing antibody geometric mean titers (GMT) to the comparator, AstraZeneca's AZD1222, as well as non-inferior seroconversion rates two weeks after priming. The extension of the Phase 3 trial evaluated safety and immunogenicity of homologous and heterologous booster vaccinations of VLA2001. This is a randomized observer-blind controlled, pivotal trial conducted in the UK in participants aged ≥18 years who were randomly assigned 2:1 to receive two doses of VLA2001 or AZD1222, 28 days apart. A booster with VLA2001 was administered to eligible participants at 7 to 8 months after priming. The primary safety outcome was the frequency and severity of any adverse event following the booster vaccination. The primary immunogenicity outcomes were the GMT and fold increase of neutralizing antibodies against SARS-CoV-2 two weeks after the booster vaccination. The study is registered under NCT04864561. A booster dose of VLA2001 is well-tolerated in both AZD1222 and VLA2001 primed participants. High neutralizing antibody titers and fold- increases were generated two weeks following a booster of VLA2001. Cross- neutralizing serological responses against Delta and the Omicron BA.4/BA.5 variants of concern are elicited following a homologous or heterologous booster dose in VLA2001 or AZD1222 primed participants, respectively. Additionally, VLA2001 induced broad T-cell responses with antigen-specific IFN-gamma producing T-cells against the Spike, the Nucleocapsid and the Membrane protein. Homologous and heterologous booster doses of VLA2001 demonstrated a favorable tolerability profile irrespective of priming and induced broadly reactive neutralizing antibodies against the ancestral virus and variants of concern, including the currently circulating BA.4/BA.5.