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

Inclusion Criteria

To be eligible for the study, each participant must satisfy all of the following criteria:

• Healthy female and male participants 18 -54 years of age.
• If female:
• is of childbearing potential and must have a negative pregnancy test prior to study vaccinations and agree to use an effective method of birth control as deemed appropriate by the investigator (e.g., hormonal contraceptive, barrier contraceptive with additional spermicide, or an intrauterine device) beginning >30 days prior to the first study vaccine administration and continuing until the end of the study.

OR

• is not of childbearing potential, defined as postmenopausal (12 months with no menses without an alternative medical cause) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy orhysterectomy).
• Phase 1b: previously received a full course (2 doses) of an authorized S protein mRNA COVID-19 vaccine (e.g. COVID-19 vaccines produced by Pfizer/BioNTech or Moderna) at least 4 months prior to enrollment.
• Sign an informed consent document indicating understanding of the purpose of and procedures required for the study and willingness to participate in the study.

Exclusion Criteria

Participants with any of the following criteria will be excluded:

• History of clinical or laboratory diagnosis of COVID-19 or SARS-CoV-2 infection.
• Phase 1b: Previous receipt of an experimental or authorized SARS-CoV-2 (COVID-19) vaccines other than an S-protein mRNA vaccine.
• Phase 1a: Previous receipt of an experimental or authorized SARS-CoV-2 (COVID-19) vaccine.
• Positive PCR or rapid antigen test for SARS-CoV-2 at screening.
• Individuals with chronic medical conditions, including any of the following:
• Diabetes mellitus Type 1 or Type 2
• Chronic pulmonary disease (e.g., COPD or Asthma)
• Hypertension (e.g., SBP >140 mmHg or DBP >90 mmHg)
• Chronic kidney disease (e.g., GFR 30 kg/m2)
• Any history of cancer requiring chemotherapy or radiation within 5years.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Lack of participant's capacity (mental, social, behavioral), in the investigator's judgement, to provide informed consent for participation in the study.
• Known or suspected impairment of immunological function, including but not limited to autoimmune diseases:
• autoimmune diseases (e.g. multiple sclerosis, type 1 diabetes, myasthenia gravis, Crohn disease and other inflammatory bowel diseases, celiac disease, systemic lupus erythematosus, scleroderma, including diffuse systemic form and CREST syndrome, systemic sclerosis, dermatomyositis polymyositis, rheumatoid arthritis, juvenile idiopathic arthritis, autoimmune thyroiditis - including Hashimoto thyroiditis, Grave's or Basedow's disease, immune thrombocytopenic purpura, autoimmune hemolytic anemia, autoimmune hepatitis, psoriasis, vitiligo, vasculitis, Guillain- Barré syndrome, Transverse myelitis, Addison's disease, Bell's Palsy and Alopecia Areata);
• secondary immunodeficiency disorders (e.g., Acquired Immunodeficiency Syndrome caused by Human Immunodeficiency Virus infection (HIV/AIDS), solid organ transplant,splenectomy);
• primary immunodeficiency disorders (e.g., common variable immune deficiency (CVID), Defective phagocytic cell function and neutropenia syndromes, complement deficiency).
• History of allergic reactions or anaphylactic reaction to any vaccine component.
• Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
• Pregnant or breastfeeding or plans to conceive from 2 weeks before the study until the end of study.
• Clinically significant abnormal physical examination, vital signs, or clinically significant abnormal values for hematology,