Safety, Tolerability, and Immunogenicity of the COVID-19 Vaccine Candidates VBI-2902a and VBI-2905a

Phase 1a:

The primary objective is to evaluate the safety and tolerability of VBI-2902a containing 5 μg of S protein in one- or two-dose regimens in healthy adults of 18-54 years of age.

The secondary objective is to evaluate the immunogenicity of VBI-2902a containing 5 μg of S protein in one- or two-dose regimens in healthy adults 18-54 years of age.

* Group G1 - 20 participants will receive VBI-2902a at a dose of 5 μg of S protein at Day 1 and placebo at Day 28. * Group G2 - 20 participants will receive VBI-2902a at a dose of 5 μg of S protein at Days 1 and 28. * Group G3 - 20 participants will receive placebo at Days 1 and 28.

An Independent Data Safety Monitoring Board (DSMB) will review blinded safety data (reactogenicity, adverse events (AEs) and safety laboratory assessments) at Day 7 after the first vaccination. The second vaccination will only be given if the DSMB confirms that Day 7 safety is acceptable and that stopping rules were not met. The DSMB will further review blinded post-vaccination safety through Day 35, 7 days after the second vaccination and through Day 56, 28 days after the second vaccination. The study will be unblinded following DSMB review of safety data collected through Day 56. Study participants will continue with study visits as planned up to 12 months of follow up after the first dose of study vaccine.

Phase 1b:

The primary objective is to evaluate the safety and tolerability of a one-dose regimen of VBI-2905a at a 5 μg dose level of S protein in healthy adults (age 18-54 years) who had been previously vaccinated with mRNA vaccines.

The secondary objective is to evaluate the immunogenicity of a one-dose regimen of VBI-2905a at a 5 μg dose level of S protein in healthy adults (age 18-54 years) who had been previously vaccinated with mRNA vaccines.

A total of 54 healthy adults, age 18-54 years, with no history of clinical or laboratory diagnosis of SARS-CoV- 2 infection or COVID-19 illness, will be enrolled in the Phase 1b part of the study. All participants in Phase 1b will have been previously vaccinated with an authorized mRNA COVID-19 vaccine, including the second dose administered at least 4 months prior to enrollment, will be randomized at a 1:1 ratio to receive, in a blinded fashion, one dose of VBI-2905a or placebo: