The rapid spread of SARS-CoV-2 continues to impact humanity on a global scale with rising total morbidity and mortality. Despite the development of several effective vaccines, new products are needed to supply ongoing demand and the needs of specific populations. We report herein a pre-specified interim analysis of the phase 2 portion of an ongoing Phase 2/3, randomized, placebo-controlled trial of a coronavirus virus-like particle (CoVLP) vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein adjuvanted with AS03 (NCT04636697). A total of 753 subjects were recruited between 25 November 2020 and 24 March 2021 into three groups: Healthy Adults (18-64 years: N=306), Older Adults ([≥] 65 years: N=282) and Adults with Comorbidities ([≥]18 years: N=165) and randomized 5:1 to receive two intramuscular doses of either vaccine CoVLP (3.75 g/dose + AS03) or placebo 21 days apart. This report presents safety, tolerability and immunogenicity data collected up to 21 days after the second dose. The immune outcomes presented include neutralizing antibody (NAb) titres and cellular (IFN-{gamma} and IL-4 ELISpot) responses. In this study, CoVLP+AS03 was well-tolerated and adverse events (AE) after each dose were generally mild to moderate and transient. Solicited AEs in Older Adults and Adults with Comorbidities were generally less frequent than in Healthy Adults. CoVLP+AS03 induced seroconversion in >35% of subjects in each group after the first dose and in [~]98% of subjects 21 days after the second dose. In all treatment groups, NAb levels were [~]10-fold higher than those in a panel of convalescent sera. A significant minority ([~]20%) of subjects had evidence of a pre-existing IFN-{gamma} response to the S protein and almost all subjects in all groups (>88%) had detectable cellular responses (IFN-{gamma}, IL-4 or both) at 21 days after the second dose. A Th1-biased response was most evident after the first dose and was still present after dose two. These data demonstrated that CoVLP+AS03 will likely be well-tolerated and highly immunogenic in adults [≥]18 years of age with and without comorbidities.
