COV-COMPARE Immunogenicity of Vaccine VLA2001 Compared to AZD1222

Approximately 4000 Adult participants will be recruited in the study. About 3000 participants aged 30 years and above will be randomized in a 2:1 ratio to receive 2 intramuscular recommended doses of either VLA2001 (n=2000) or AZD1222 (n=1000). In addition, approximately 1000 subjects aged 18-29 years will participate in this study in a non-randomized, open-label fashion to receive VLA2001. The 2 doses of vaccination for both vaccines will be administered 28 days apart, on Days 1 and 29. All visits will be conducted at the clinical site on an outpatient basis.

All participants - except those who already received a licensed COVID-19 vaccine outside of the study - will be offered a booster dose with VLA2001 between Jan and Mar 2022 and will have a follow-up visit 14 days (Visit B2) and 6months after the booster dose.

Approximately 660 Adolescent participants were planned to be recruited and randomized in a 1:1 ratio to receive 2 intramuscular doses of either VLA2001 (n=330) or placebo (n=300). Participants in the placebo group will receive a 2-dose primary immunization with VLA2001 on Day 85 and the second vaccination 28 days later. For safety reasons, the first 16 adolescents will be enrolled in an open label, non-randomized manner (sentinel dosing).

Recruitment of adolescent participants has been stopped after recruitment of 6 randomized participants (3 randomized to VLA2001 and 3 participants randomized to placebo) due to the low recruitment rate. The study design ensures a safety follow-up of at least 6 months after the last VLA2001 vaccination/booster for all enrolled study participants

Participants will be provided with an electronic Diary (e-Diary) and will be trained to record specifically solicited systemic and local symptoms daily as well as any additional AEs during follow-up period after each of both vaccinations up to the next visit to the site until Day 43 visit has been completed.

Inclusion criteria

• Participants must have read, understood, and signed the informed consent form (ICF).
• Participants of either gender aged 12 years and older at screening.
• Medically stable
• Must be able to attend all visits of the study and comply with all study procedures,
• Women of childbearing potential (WOCBP) must be able and willing to use at least 1 highly effective method of contraception for a minimum of 3 months after the last dose of study vaccine.
• WOCBPs must have a negative pregnancy test prior to each vaccination.

Exclusion criteria

• Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration.
• History of allergy to any component of the vaccine.
• Significant infection (e.g. positive SARS-CoV-2 RT-PCR) or other acute illness, including fever > 100 °F (> 37.8 °C) 48 hours before vaccination.
• Participant has a known or suspected defect of the immune system
• Participant has a history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.
• Participant has a history of malignancy in the past 5 years other than squamous cell or basal cell skin cancer. If there has been surgical excision or treatment more than 5 years ago that is considered to have achieved a cure, the participant may be enrolled. A history of hematologic malignancy is a permanent exclusion. Participants with a history of skin cancer must not be vaccinated at the previous tumour site.
• History of drug dependency or current use of drug of abuse or alcohol abuse at screening.
• Significant blood loss (> 450 mL) or has donated 1 or more units of blood or plasma within 6 weeks prior to the expected day of randomization (Visit 1).
• History of clinically significant bleeding disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
• Severe and uncontrolled ongoing autoimmune or inflammatory disease History of Guillain-Barre syndrome or any other demyelinating condition.
• Any other significant disease, disorder or finding which in the opinion of the investigator may significantly increase the risk to the volunteer

Prior/concomitant therapy:

• Receipt of immunoglobulin or another blood product within the 3 months before expected day of randomization (visit 1) in this study or those who expect to receive immunoglobulin or another blood product during this study.
• Receipt of medications and or vaccinations intended to prevent COVID-19.
• Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1).
• Any member of the study team or sponsor.
• An immediate family member or household member of the study's personnel.

Booster Vaccination (Adults and Adolescents)

In addition to the above-described eligibility criteria, the following criteria must be met:

• Participant has not received another licensed COVID-19 vaccine during the study