The main purpose of Part A of this study is to evaluate the safety and tolerability of mRNA-1345 vaccine and to demonstrate the efficacy of a single dose of mRNA-1345 vaccine in the prevention of a first episode of RSV-associated lower respiratory tract disease (RSV-LRTD) as compared with placebo from 14 days postinjection through 12 months.

The main purpose of Part B of this study is to evaluate the safety, tolerability and immunogenicity of a booster dose (BD) of mRNA-1345 administered 24 months after the primary dose.

The study will be conducted in 2 phases: Phase 2 and Phase 3. In the Part A Phase 2 segment, up to 2,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio.

In the Part A Phase 3 segment, approximately 35,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio.

In the Part B substudy, 1500 participants who received a dose of mRNA-1345 in Part A Phase 3 will be randomly assigned in a 2:1 randomization ratio to receive a single BD injection of either mRNA-1345 at the selected dose or placebo.

Key Inclusion Criteria (Part A):

• Adults ≥ 60 years of age who are primarily responsible for self-care and activities of daily living. Participants may have one or more chronic medical diagnoses (including chronic heart failure [CHF] and chronic obstructive pulmonary disease [COPD]), but should be medically stable
• Body mass index from ≥18 kilograms (kg)/square meter (m^2) to ≤35 kg/m^2

Key Inclusion Criteria (Part B):

• Randomized to and were subsequently vaccinated with the mRNA-1345 study injection in Part A at least 21 months prior to Screening.

Key Exclusion Criteria (Part A):

• Participation in another clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of the Day 1 study injection.
• Current participation in research involving receipt of any investigational RSV product
• History of a serious reaction to any prior vaccination or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization.
• Received or plans to receive any non-study vaccine within 28 days before or after the Day 1 study injection.

Key Exclusion Criteria (Part B):

• Participation in another clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of BD study injection (BD Day 1).
• History of a serious reaction to any prior vaccination, or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization.
• Received or plans to receive any non-study vaccine (including authorized or approved vaccines for the prevention of coronavirus disease 2019 (COVID-19) regardless of type of vaccine) within 14 days before or after the BD Day 1 study injection.
• Received or plans to receive any commercial RSV vaccination at any time prior to BD study injection (BD Day 1) or during the substudy.

Other inclusion and/or exclusion criteria may apply.