Safety and Immunogenicity of RNA-based Vaccines Against SARS-CoV-2 Variants in Healthy Participants

Inclusion Criteria:

- Have given informed consent by signing the informed consent form (ICF) before
initiation of any trial-specific procedures.

- Volunteers who at the time of consent are:

- Part A: 18 to 55 years old.

- Part B and Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56
to 85 years old).

- For Cohorts 1 to 5: In Part A, who have received BNT162b2 vaccine (30 µg, two-dose
regimen) in either a clinical trial or as part of the governmental vaccination
programs at least 6 months before Visit 0. Participants who are currently enrolled in
the Phase III BNT162-02 / C4591001 trial, have already been unblinded, and have
previously received two doses of BNT162b2 at least 6 months earlier can be included
(for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the BNT162-02 /
C4591001 trial is mandatory). At enrollment into Part B of this trial, their
participation in the BNT162-02 / C4591001 trial will be terminated. Participants
should have not experienced COVID-19 based on medical history.

- For Cohort 6: Are COVID-19 vaccine-naïve and have not experienced COVID-19 based on
their medical history.

- Are willing and able to comply with all scheduled visits, vaccination plan, laboratory
tests, lifestyle considerations, and other trial procedures.

- Are overall healthy at Visit 0 in the clinical judgment of the investigator based on
the medical history, clinical assessment (including physical examination, vital signs,
blood and urine clinical laboratory tests, 12-lead electrocardiogram (ECG), and oral
swab for Nucleic Acid Amplification-based Test (NAAT)-based Severe Acute Respiratory
Syndrome Coronavirus 2 (SARS-CoV-2) testing).

- Note: Healthy volunteers with pre-existing stable disease, defined as disease not
requiring significant change in therapy or hospitalization for worsening disease
during the 12 weeks before Visit 0, can be included.

- Note: Volunteers who had hepatitis C (HCV) infection, but have completed curative
treatment based on the medical history can be included. Volunteers who had or have
hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history
cannot be included.

- Agree not to enroll in another trial of an Investigational Medicinal Product (IMP),
starting after Visit 0 and continuously until the last planned visit in this trial.

- Women of childbearing potential (WOCBP) must test negative in a urine beta-human
chorionic gonadotropin (β-HCG) test at Visits 0 and 1.

- WOCBP must agree to practice a highly effective form of contraception starting at
Visit 0 and continuously until 28 days after their last IMP administration in this
trial.

- WOCBP must confirm that they practiced an acceptable form of contraception for the 14
days prior to Visit 0.

- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction starting after Visit 0 and continuously until 28 days after their last
IMP injection in this trial.

- Men who are sexually active with a WOCBP and have not had a vasectomy must agree to
use a highly effective form of contraception with their female partner of childbearing
potential starting after Visit 0 and continuously until 28 days after their last IMP
injection in this trial.

- Men must be willing to refrain from sperm donation, starting after Visit 0 and
continuously until 28 days after their last vaccination.

- For Part C, Cohorts 7, 8, and 9: have received two or three documented doses of any
authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] or the Moderna
vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 infection from January
2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2
Omicron infections).

- Note: The interval between the last COVID-19 RNA-based vaccine administered and
randomization should be >4 months. The latest prior diagnosed SARS-CoV-2 infection
should be at least 2 months before randomization. The latest SARS-CoV-2 infection
should be documented with a result from a NAAT (as a preferable option). In case no
historic NAAT result is available proving prior SARS-CoV-2 infection, the local
positive result of SARS-CoV-2 N-binding antibodies done at screening will be
sufficient.

Exclusion Criteria:

- Any existing condition which may affect vaccine injection and/or assessment of local
reactions assessment, e.g., tattoos, severe scars, etc.

- Any bleeding diathesis or condition associated with prolonged bleeding that would, in
the opinion of the investigator, contraindicate intramuscular injection.

- Any medical or psychiatric condition including recent (within the past year) or active
suicidal ideation/behavior or laboratory abnormality that, in the investigator's
judgment, make the participant inappropriate for the trial.

- Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness
within 48 h prior to Day 1/IMP injection in this trial.

- Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis,
myocardial infarction, congestive heart failure, cardiomyopathy or clinically
significant arrhythmias.

- History of COVID-19 and/or clinical (based on COVID-19 symptoms/signs alone, if a SARS
CoV 2 NAAT result was not available) or microbiological (based on COVID-19
symptoms/signs and a positive SARS CoV 2 NAAT result) evidence of prior infection with
SARS CoV 2 at screening (Visit 0).

- Note: not applicable for Part C.

- History of Guillain-Barré syndrome.

- Known or suspected immunodeficiency.

- History of severe adverse reaction associated with a vaccine and/or severe allergic
reaction (e.g., anaphylaxis) to any component of the trial IMPs.

- History or known allergy, hypersensitivity, or intolerance to the trial IMP including
any excipients of the IMPs in this trial.

- Have received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as
a course of two doses approximately 21 days apart).

- Note: not applicable for Part C.

- Have received a live or live attenuated vaccine within 28 days prior to Day 1/IMP
injection.

- Have received any other vaccines within 14 days before or after any IMP injection,
e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible standard or
care vaccinations should be planned with the trial IMP administrations in mind.

- Individuals who receive treatment with radiotherapy or immunosuppressive therapy,
including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids
are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent),
e.g., for cancer or an autoimmune disease, or planned receipt throughout this trial.
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes)
corticosteroids are permitted.

- Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP
administration or planned receipt throughout this trial.

- Participation in other trials involving IMP within 28 days or 5 half-lives (whichever
is longer) prior to Visit 1 and/or during trial participation, besides participation
in trials with BNT162b2.

- Are pregnant or breastfeeding or are planning pregnancy within 28 days after last IMP
treatment.

- Are vulnerable individuals as per International Conference on Harmonisation (ICH) E6
definition, i.e., are individuals whose willingness to volunteer in a clinical trial
may be unduly influenced by the expectation, whether justified or not, of benefits
associated with participation, or of a retaliatory response from senior members of a
hierarchy in case of refusal to participate.

- For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized
COVID-19 vaccines.

- For Part C, Cohorts 7, 8, and 9: Vaccination with any COVID-19 vaccine after
SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was
a high prevalence of SARS-CoV-2 Omicron infections).