This is a multicentre, randomized, observer-blind, active-controlled, superiority, study in adults to compare the immunogenicity of VLA2001 to AZD1222 in terms of GMT of SARS-CoV-2-specific neutralising antibodies. Furthermore, VLA2001 will be compared to placebo in an adolescent population.

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:

1. Participants must have read, understood, and signed the informed consent form (ICF).
2. Participants of either gender aged 12 years and older at screening.
3. Medically stable
4. Must be able to attend all visits of the study and comply with all study procedures,
5. 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.
6. WOCBPs must have a negative pregnancy test prior to each vaccination.

Exclusion Criteria:

1. Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration.

2. History of allergy to any component of the vaccine.

3. 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.

4. Participant has a known or suspected defect of the immune system

5. Participant has a history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.

6. 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.

7. History of drug dependency or current use of drug of abuse or alcohol abuse at screening.

8. 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).

9. History of clinically significant bleeding disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.

10. Severe and uncontrolled ongoing autoimmune or inflammatory disease History of Guillain-Barre syndrome or any other demyelinating condition.

11. 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:

12. 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.

13. Receipt of medications and or vaccinations intended to prevent COVID-19.

14. Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1).

15. Any member of the study team or sponsor.

16. 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:

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

study participants aged 18-29 years at the time of enrolment are unblinded, study participant aged 12-18 and 30 years above at the time of enrolment are blinded (sentinel group is unblinded) until 28 days after vaccination on day 208, when all participants will be unblinded.