First episode of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated LRTD during the first season was assessed. The case definition for RSV-confirmed LRTD is as follows: Presence of at least one RSV-positive swab detected by RT-PCR.

Analysis was performed on the modified Exposed Set (mES), which included all participants who received at least the first dose of the study intervention and who do not report an RSV-confirmed Acute Respiratory Illness (ARI) prior to 2 weeks (\

Efficacy of a single dose of the RSVPreF3 OA vaccine was assessed against RSV A and/or B confirmed LRTD over several seasons according to the case definition.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2 administration.

Efficacy of annual revaccination doses of the RSVPreF3 OA vaccine was assessed against RSV A and/or B confirmed LRTD over several seasons according to the case definition.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2 administration.

Efficacy of a single dose of the RSVPreF3 OA vaccine was assessed against LRTD episode caused by RSV A and B subtype over 3 seasons according to the case definition.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2 administration.

Efficacy of a single dose and 1 annual revaccination dose of the RSVPreF3 OA vaccine was assessed against LRTD episode caused by RSV A and B subtype over 3 seasons according to the case definition.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses was assessed against RSV A and/or B confirmed LRTD episode according to the case definition, in the following age categories: greater than or equal to (≥) 65 years of age (YOA), ≥70 YOA and ≥80 YOA.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses was assessed against RSV A and/or B confirmed LRTD episode according to the case definition, by RSV season as follows: VE after each season includes the first occurrence of episodes reported from Day 15 post vaccination at first season, and for the next seasons, excluding analysis of participants who already reported a case in the previous season. The RSV season may be extended based on epidemiology data.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. Analysis is presented based on the groups at each season (RSVPreF3 group for Season 1, RSV_1_dose and RSV_annual groups for Seasons 2 and 3, Placebo group for Season 1, 2 and 3).

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses was assessed against RSV A and/or B confirmed LRTD episode according to the case definition, by years after vaccination as follows: VE at each year includes the first occurrence of episodes reported from Day 14 post vaccination at first year, and for the next years, excluding analysis of participants who already reported a case in the previous year.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. Analysis is presented based on the groups at each season (RSVPreF3 group for Year 1, RSV_1_dose and RSV_annual groups for Years 2 and 3, Placebo group for Years 1, 2 and 3).

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and/or B associated LRTD episode by baseline comorbidities using Charlson Comorbidity Index. Low/medium Risk = Participants with co-morbidity score at baseline less than or equal to 3 (Charlson Index); High Risk = Participants with co-morbidity score at baseline greater than 3 (Charlson Index).

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and/or B associated LRTD episode by baseline comorbidities of interest divided into 2: cardiorespiratory conditions such as chronic obstructive pulmonary disease (COPD), asthma, any chronic respiratory or pulmonary disease, and endocrinometabolic conditions such as diabetes mellitus type 1 or 2, chronic heart failure and advanced liver or renal disease.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and /or B associated LRTD episode according to the case definition, by baseline frailty status of frail, pre-frail and fit. Frail = Participants with a walking speed of less than (<) 0.4 meters per second (m/s) or who were not able to perform the test; Pre-Frail = Participants with a walking speed between 0.4-0.99 m/s; Fit = Participants with a walking speed of ≥1 m/s.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV A and/or B associated severe LRTD episode. Case definition for RSV-confirmed severe LRTD: An RT-PCR confirmed case of RSV-associated severe LRTD is characterized by presence of lower respiratory signs or an LRTD episode assessed as severe by the investigator (Severe LRTD case definition 1) or presence of an LRTD with need for oxygen supplementation or need for positive airway pressure therapy or need for other types of mechanical ventilation (Severe LRTD case definition 2) and with at least one RSV positive swab detected by RT-PCR.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against RSV confirmed A and/or B associated ARI episode. A case of RT-PCR confirmed RSV-associated ARI is characterized by the presence of respiratory symptoms/signs for at least 24 hours OR respiratory symptom/sign + systemic symptom/sign for at least 24 hours with at least one RSV-positive swab detected by RT-PCR.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

Efficacy of a single dose of the RSVPreF3 OA vaccine and annual revaccination doses is assessed against any ARI and any LRTD.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

RSV infection was confirmed by RT-PCR.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

A diagnosis of respiratory disease included: acute respiratory infections, other diseases of upper respiratory tract, pneumonia and influenza, chronic obstructive pulmonary disease and allied conditions, pneumoconioses and other lung diseases due to external agents, other diseases of respiratory system.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

RSV infection was confirmed by RT-PCR.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

RSV infection was confirmed by RT-PCR.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

For this outcome measure, the Health Related -Quality of life (HR-QOL) score is measured by Flu-PRO questionnaire version 2.0. The Flu-PRO is a 32 items daily diary, which assesses influenza signs across 6 body systems- nose, throat, eyes, chest/respiratory, gastrointestinal and body/systemic. The objective of this outcome measure was to present data only for chest/respiratory system after a single dose and after annual revaccination. The FLU-PRO score was computed as the mean score across questionaire items for chest/respiratory body system, with the scores ranging from 0 (symptom free) to 4 (very severe symptoms).

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

The Flu-PRO questionnaire version 2.0 is a 32 items daily diary, which assesses influenza signs across 6 body systems- nose, throat, eyes, chest/respiratory, gastrointestinal and body/systemic. The FLU-PRO total score was computed as the mean score across all 32 items of the questionaire for all 6 body systems, with the total scores ranging from 0 (symptom free) to 4 (very severe symptoms).

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

The EQ-5D is a general health utility questionnaire with health states, defined through 5 dimensions- mobility, self-care, usual activities, pain/ discomfort and anxiety/ depression. A participant who responds 1 (no problem/no symptom) to all 5 items has a profile "11111" and similarly a participant who responds 3 (the highest level of difficulty or symptom) to all items has a profile "33333". The health states indicated in these 5 dimensions are converted and presented as a single mean index value as recommended by EuroQol group, where values range from 0 (worst) to 1 (full health).

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

SF-12 is a health survey with 12 questions, covering 8 domains- physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. Summary scores are computed from these domains for the physical and mental component. The total score of the SF-12 questionnaire is evaluated on a scale from 0 to 100, with a higher score indicating a better perceived health-related quality of life.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

The duration in days of RT-PCR confirmed RSV A and/or B ARI and LRTD episodes are described.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis.

RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes were reported. Fever was defined as a temperature ≥38.0 degrees Celsius (°C) by any route.

Analysis was performed on the mES. Only participants with data available for symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes at specified timepoints were included in analysis.

RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes were reported. Fever was defined as a temperature ≥38.0 degrees Celsius (°C) by any route.

Analysis was performed on the modified Exposed set for Dose 2 (mES-Dose 2), which included all participants who received the first and second doses of the study intervention, and who did not report an RSV-confirmed ARI prior to Day 15 after each vaccination. Only participants with data available for symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes at specified timepoints were included in analysis.

RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes were reported. Fever was defined as a temperature ≥38.0 degrees Celsius (°C) by any route.

Analysis was performed on the mES-Dose 2. Only participants with data available for symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B ARI episodes at specified timepoints were included in analysis. Only participants in NH were included in this analysis.

RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes were reported. Fever was defined as a temperature ≥38.0°C by any route.

Analysis was performed on the mES-RSV. Only participants with data available for symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes at specified timepoints were included in analysis.

RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes were reported. Fever was defined as a temperature ≥38.0°C by any route.

Analysis was performed on the mES-Dose 2. Only participants with data available for symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes at specified timepoints were included in analysis.

RSV infection was confirmed by RT-PCR, and the symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes were reported. Fever was defined as a temperature ≥38.0°C by any route.

Analysis was performed on the mES-Dose 2. Only participants with data available for symptoms/signs and supportive therapy use associated with RT-PCR confirmed RSV A and/or RSV B LRTD episodes at specified timepoints were included in analysis. Only participants in NH were included in this analysis.

RSV A and/or B ARI and LRTD episodes were assessed as "mild", "moderate" or "severe" by the investigator after the single dose and after annual revaccination. Mild = an ARI/LRTD episode which is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. Moderate = an ARI/LRTD episode which is sufficiently discomforting to interfere with normal everyday activities. Severe = an ARI/LRTD episode which prevents normal, everyday activities.

Analysis was performed on the mES-RSV. Only participants with data available at specified timepoints were included in analysis. For single dose evaluation, participants from the RSV_annual group who received RSVPreF3 OA investigational vaccine at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2. For annual dose evaluation, participants from the RSV_1_dose group who received Placebo at Dose 2 contributed to Season 1 data only and were censored starting from Dose 2.

The RSVPreF3 IgG antibody concentrations are expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (EU/mL).

Analysis was performed in a subset of participants from the Per Protocol Set for immunogenicity (PPSi), which included participants who received at least the first dose of the study intervention, have post-vaccination immunogenicity data available, and did not meet protocol deviations that lead to exclusion. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

The RSV A neutralizing antibody titers are expressed as geometric mean titers (GMTs).

Analysis was performed in a subset of participants from the PPSi. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

RSV B neutralizing antibodies are expressed as GMTs.

Analysis was performed on PPSi. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

Any solicited event is defined as the occurrence of any solicited adverse event (AE) regardless of intensity grade or relation to study vaccination. Grade 3 = an event which prevented normal, everyday activities. The assessed administration site events include pain, erythema and swelling.

Analysis was performed on a subset of participants from the solicited safety set (SSS), which included participants who received at least the first dose of the study intervention and with the solicited administration site events diary card data available after the corresponding vaccination for the specified duration. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

Any solicited event is defined as the occurrence of any solicited adverse event (AE) regardless of intensity grade or relation to study vaccination. Grade 3 = an event which prevented normal, everyday activities. The assessed solicited systemic events include arthralgia, fatigue, fever, headache and myalgia. Fever is defined as a temperature ≥ 38.0°C by any route. Grade 3 fever is defined as temperature >39°C by any route.

Analysis was performed on a subset of participants from the solicited safety set (SSS), which included participants who received at least the first dose of the study intervention and with the solicited systemic events diary card data available after the corresponding vaccination for the specified duration. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

Analysis was performed on a subset of participants from the solicited safety set (SSS), which included participants who received at least the first dose of the study intervention and with the solicited administration site events diary card data available after the corresponding vaccination for the specified duration. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

Analysis was performed on a subset of participants from the solicited safety set (SSS), which included participants who received at least the first dose of the study intervention and with the solicited systemic events diary card data available after the corresponding vaccination for the specified duration. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

An unsolicited AE is defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside of the specified period of follow-up for solicited symptoms was reported as an unsolicited AE. Any= occurrence of the event regardless of intensity grade or relation to the study vaccination.

Analysis is performed on the Exposed Set, which included all participants that received at least the first vaccination. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or in other situations that were considered serious per medical or scientific judgment. Any = occurrence of any SAE regardless of intensity grade or relation to study vaccination.

Analysis is performed on the Exposed Set, which included all participants that received at least the first vaccination. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

pIMDs aredefined as a subset of Adverse Events of Specific Interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Any= occurrence of any pIMD regardless of intensity grade or relation to the study vaccination.

Analysis is performed on the Exposed Set, which included all participants that received at least the first vaccination. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

Related SAEs that occur throughout the study are assessed. Related SAEs= Any SAE related to investigational vaccine or related to study participation or to a GSK concomitant medication/vaccine as assessed by the investigator.

Analysis was performed on the Exposed Set. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

Fatal SAEs that occur throughout the study are assessed. Fatal SAEs= Any SAEs leading to deaths.

Analysis was performed on the Exposed Set. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.

Related pIMD = pIMD assessed by the investigator as related to the study vaccination.

Analysis was performed on the Exposed Set. Only participants with data available at specified timepoints were included in analysis. Analysis is presented dose-wise after first dose administration and annual revaccinations.