Safety, Tolerability, and Immunogenicity of Trivalent Coronavirus Vaccine Candidate VBI-2901e With E6020 Adjuvant

VBI-2901e is an investigational trivalent COVID-19 vaccine candidate that comprises enveloped virus-like particles (eVLPs) expressing the spike proteins of the betacoronaviruses SARS-CoV-2, SARS-CoV-1 and MERS-CoV and the adjuvants aluminum phosphate and E6020 (a toll-like receptor 4 agonist). The study will enroll participants 18 to 40 years of age who have previously received two or more vaccinations with licensed COVID-19 vaccine(s) and will test one or two intramuscular doses of VBI-2901e containing 5 μg of SARS-CoV-2 spike protein, 165 µg of aluminum phosphate and 1, 3 or 10 µg of E6020. VBI-2901e is designed to induce neutralizing antibody and cell-mediated immune responses against multiple coronavirus respiratory disease strains and variants/subvariants of SARS-CoV-2. This is a randomized, open-label adjuvant dose-escalation study. The study will enroll healthy adults, aged 18 to 40 years of age, who had previously received two or more vaccinations with licensed COVID-19 vaccine(s), with the final dose administered a minimum of 6 months (24 weeks) prior to enrollment; have a negative PCR or rapid antigen SARS-CoV-2 test at screening; and have met all other eligibility criteria. Participants with a history of mild COVID-19 illness are eligible if they fully recovered a minimum of 6 months (24 weeks) prior to enrollment. A total of 60 participants will be enrolled in the study. Study groups will be enrolled sequentially in an E6020 dose-escalating fashion starting with 20 participants to receive VBI-2901e with 1 µg of E6020 (Group G1), followed by 20 participants to receive VBI-2901e with 3 µg of E6020 (Group G2) and 20 participants to receive VBI-2901e with 10 µg E6020 (Group G3). Within each study group, participants will be randomized at a 1:1 ratio to receive one or two doses of VBI-2901e. Group G1 * Subgroup G1-A: 10 participants to receive VBI-2901e at 5 µg with 1 µg E6020 per dose on Day 1. * Subgroup G1-B: 10 participants to receive VBI-2901e at 5 µg with 1 µg E6020 per dose on Day 1 and Day 28. Group G2 * Subgroup G2-A: 10 participants to receive VBI-2901e at 5 µg with 3 µg E6020 per dose on Day 1. * Subgroup G2-B: 10 participants to receive VBI-2901e at 5 µg with 3 µg E6020 per dose on Day 1 and Day 28. Group G3 * Subgroup G3-A: 10 participants to receive VBI-2901e at 5 µg with 10 µg E6020 per dose on Day 1. * Subgroup G3-B: 10 participants to receive VBI-2901e at 5 µg with 10 µg E6020 per dose on Day 1 and Day 28. The objective of the study is to select the optimal dose level of E6020 adjuvant (1, 3 or 10 μg) and number of doses (1 or 2 doses) of trivalent coronavirus vaccine candidate VBI-2901e in individuals who had been vaccinated against COVID-19 previously. To achieve this objective, the study will evaluate outcomes including safety and tolerability as well as antibody and T cell immune responses against the original SARS-CoV-2 ancestral strain, selected SARS-CoV-2 variants, SARS-CoV-1 and MERS-CoV.