This study is designed to evaluate whether the adjuvanted recombinant zoster vaccine (RZV) or the adjuvanted respiratory syncytial virus PreFusion protein 3 (RSVPreF3) vaccine can attenuate the progression of coronary plaque in adult individuals at risk for cardiovascular events.

Inclusion Criteria:

• Participants, including participants with a caregiver who, in the opinion of the investigator, can and will comply with the requirements of the protocol.

• Written or witnessed informed consent obtained from the participant prior to performance of any study-specific procedure.

• Medically stable patients as established by medical history and clinical examination at screening.

• Male or female participants >=50 years of age (YOA) at the time of the first study intervention administration.

• Participants with documented history of coronary artery calcium (CAC) and two or more risk factors for cardiovascular disease.

• Participants with estimate glomerular filtration rate (eGFR) >=45 mL/min/1.73m^2.

• Participants who can undergo serial CCTA.

• Participants with no planned changes in medical therapies through the course of the study.

• Participants of non-childbearing potential may be enrolled in the clinical study.

• Participant of childbearing potential may be enrolled in the study if the participant:

  • has practiced adequate contraception for at least 30 days prior to study intervention administration, and
  • has a negative pregnancy test within 24 hours prior to the study intervention administration and prior to each CCTA, and
  • has agreed to continue adequate contraception during the entire duration of the study and for 8 weeks after completion of the study.

Exclusion Criteria:

Cardiovascular conditions

• Prior atherosclerotic cardiovascular disease (ASCVD) event.
• History or planned coronary artery bypass grafting (CABG), any cardiovascular surgery, percutaneous coronary intervention (PCI), or valvular intervention.
• Heart failure with Class III or IV symptoms according to the New York Heart Association and/or unstable heart failure at the screening visit.

Other medical conditions

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Acute or unstable chronic conditions, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination and/or laboratory screening tests.
• Recurrent history or uncontrolled neurological disorders or any neuroinflammatory, congenital neurological conditions, encephalopathies, or seizures.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the clinical study.
• Condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study.
• History of malignancy <=5 years, radiation therapy or systemic therapy prior to signing informed consent.
• Any history of dementia or any medical condition that moderately or severely impairs cognition.

Prior/Concomitant therapy

• Previous vaccination against Herpes Zoster (HZ) (investigational or licensed vaccine) and/or planned administration of vaccination against HZ during the study period other than the vaccine administered during the study.
• Previous vaccination with an RSV vaccine (investigational or licensed vaccine) and/or planned administration of an RSV vaccine during the study period other than the adjuvanted RSVPreF3 vaccine administered during the study.
• Use of any investigational or non-registered product other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period.
• Administration of immunoglobulins or other blood products or plasma derivatives during the period starting 90 days before the study intervention or planned administration during the study period.
• Chronic administration of immune-modifying drugs and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.
• Planned administration/administration of a vaccine in the period starting 30 days before the first dose/each dose and ending 30 days after the last dose/each dose of study intervention(s) administration, with the exception of SARS-CoV-2 and inactivated seasonal influenza (flu) vaccine which can be administered up to 14 days before or 14 days after study intervention administration.

Prior/Concurrent clinical study participation

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention drug/invasive medical device.
• Contraindications to CCTA.

Other exclusion criteria

• Bedridden participants.
• Pregnant or lactating participant.
• History of current chronic alcohol consumption and/or drug abuse, based on investigator's judgment.
• Any study personnel or their immediate dependents, family, or household members.

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

This study will be conducted in an observer-blind manner.