Safety, Tolerability, and Immunogenicity of Trivalent Coronavirus Vaccine Candidate VBI-2901a

VBI-2901a is an investigational trivalent COVID-19 vaccine candidate that comprises enveloped virus-like particles (eVLPs) expressing the spike proteins of the beta-coronaviruses SARS-CoV-2, SARS-CoV-1 and MERS-CoV. The study will enroll participants 18 to 64 years of age who have previously received two or more vaccinations with a licensed COVID-19 vaccine(s) and will test two intramuscular doses of VBI-2901a containing 5 µg or 10 µg of spike protein and one dose of VBI-2901a containing 10 µg of spike protein. VBI-2901a eVLPs are formulated with 0.33 mg of aluminum phosphate (alum) adjuvant per dose. VBI-2901a is designed to induce neutralizing antibody and cell-mediated immune responses against multiple coronavirus respiratory disease strains and variants of SARS-CoV-2. This is a randomized, open-label Phase 1 study. The study will enroll adults, aged 18 to 64 years, who are healthy or in stable health; had previously received two or more vaccinations with a 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 99 participants will be randomized at a 1:1:1 ratio to the following study groups: Group G1: 33 participants to receive two doses of VBI-2901a at 5 µg per dose at Day 1 and Day 56. Group G2: 33 participants to receive two doses of VBI-2901a at 10 µg per dose at Day 1 and Day 56. Group G3: 33 participants to receive one dose of VBI-2901a at 10 µg per dose at Day 1. The total study duration for each vaccinated subject is 48 weeks (336 days) after administration of the first dose of study vaccine. During the study, the participant will make 9 visits to the study site, including the screening visit. The objective of the study is to select the optimal dose level (5 µg or 10 µg) and number of doses (1 or 2 doses) of trivalent coronavirus vaccine candidate VBI-2901a 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 SARS-CoV-2 ancestral (Wuhan) strain, selected SARS-CoV-2 variants, SARS-CoV-1 and MERS-CoV.