A Study to Assess the Safety, Tolerability, and Immunogenicity of RSVpreF in Adults at High Risk of Severe RSV Disease

Substudy A Inclusion Criteria:

• Capable of giving signed informed consent as described per protocol.
• Participants ≥18 to <60 years of age at study enrollment.
• Life expectancy ≥12 months (365 days) in the opinion of the investigator at enrollment.
• Participants who are willing and able to comply with all scheduled visits, vaccination plan, lifestyle considerations, and other study procedures.
• Participants who are considered at high risk of RSV disease by virtue of the following:
• Adults with chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus).

Chronic medical conditions for this substudy are defined as:

• Duration greater than 6 months.
• Stable disease not requiring a significant change in therapy in the previous 6 weeks or hospitalization for worsening disease within 12 weeks before receipt of study intervention.
• Requires regular medical follow-up or ongoing medication or hospitalization in the previous year.
• Additional groups at high risk include:
• Residents of nursing homes and other long-term care facilities.

Substudy A Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.
• Participants who do not have adequate deltoid muscle mass to allow intramuscular vaccination, in the opinion of the investigator.
• Serious chronic disorder, including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• 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.

Note: Specific criteria for participants with known stable infection with HIV can be found in protocol.

• Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, immunosuppressive monoclonal antibodies, systemic corticosteroids*, eg, for cancer or an autoimmune disease, or radiotherapy, from 60 days before study intervention administration or planned receipt throughout the study.

*Applies to systemic corticosteroids administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent (eg, for cancer or an autoimmune disease). Systemic corticosteroids administered at a dose of <20 mg/day of prednisone or equivalent are permitted. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, or ears) corticosteroids are permitted.

• Receipt of blood/plasma products or immunoglobulin within 60 days before study intervention administration or planned receipt of these medications prior to the final blood draw.

Note: Monoclonal antibodies with targeted mechanisms of action used in the management of chronic illnesses (eg, migraine headaches, osteoporosis) are permitted, provided they do not meet exclusion criterion 7.

• Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
• Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-month follow-up visit.
• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervise