Reactions were collected in the e-diary including redness, swelling, and pain at the injection site. Exact 2-sided CI was calculated based on the Clopper and Pearson method.

Redness and swelling were graded as mild (>2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), and severe (>10.0 cm).

Pain at the injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), and severe (prevents daily activity).

Safety population included all participants who received at least 1 dose of the study intervention (20vPnC, 13vPnC, PPSV23 or saline) and had safety follow-up after any vaccination. Here, "Number of Participants Analyzed"=number of participants with any e-diary data reported after 20vPnC or 13vPnC.

Events were collected in the e-diary including fever, headache, fatigue, muscle pain, and joint pain. Exact 2-sided CI was calculated based on the Clopper and Pearson method.

Fever was categorized as ≥38.0 degree Celsius (°C), ≥38.0°C to 38.4°C, >38.4°C to 38.9°C, >38.9°C to 40.0°C, and >40.0°C.

Fatigue, headache, muscle pain, and joint pain were graded as mild (does not interfere with activity), moderate (some interference with activity), and severe (prevents daily activity).

Safety population included all participants who received at least 1 dose of the study intervention (20vPnC, 13vPnC, PPSV23 or saline) and had safety follow-up after any vaccination. Here, "Number of Participants Analyzed" is number of participants with any e-diary data reported after 20vPnC or 13vPnC.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Safety population included all participants who received at least 1 dose of the study intervention (20vPnC, 13vPnC, PPSV23 or saline) and had safety follow-up after any vaccination.

An SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; resulted in congenital anomaly/birth defect or that was considered to be an important medical event.

Safety population included all participants who received at least 1 dose of the study intervention (20vPnC, 13vPnC, PPSV23 or saline) and had safety follow-up after any vaccination.

OPA titers were determined for the 13 matching pneumococcal serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F. GMTs and 2-sided CIs were calculated by exponentiating the Least Square (LS) means and the corresponding CIs based on analysis of log-transformed OPA titers using a regression model with vaccine group, sex, smoking status, age at vaccination in years (continuous), baseline log-transformed OPA titers, and country.

Participants analyzed=Evaluable 13-matched immunogenicity population (for any serotype) included participants who were enrolled, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major protocol deviations (PDs). Number Analyzed=participants evaluable for this outcome measure (OM) at specified row.

OPA titers were determined for serotypes: 8, 10A, 11A, 12F, 15B, 22F, and 33F. GMTs and 2-sided CIs were calculated by exponentiating the LS means and the corresponding CIs based on analysis of log-transformed OPA titers using a regression model with vaccine group, sex, smoking status, age at vaccination in years (continuous), baseline log-transformed OPA titers, and country.

Participants Analyzed=Evaluable 7-additional immunogenicity population (for any serotype) included participants who were enrolled, received 20vPnC in the 20vPnC/saline group or received both vaccinations in the 13vPnC/PPSV23 group, had at least 1 valid OPA titers for any of the 7 additional serotypes from the blood collection 27 to 49 days after Vaccination 1 or 2 respectively, had no other major PDs. Number Analyzed=participants evaluable for this OM at specified row.

GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student's t distribution), for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

Participants Analyzed=Evaluable 13-matched immunogenicity population (for any serotype) included participants who were enrolled, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major PDs. Number analyzed in each row=participants evaluable with OPA titers available at both timepoints at specified serotype.

GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student's t distribution), for serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F.

Participants Analyzed=Evaluable 7-additional immunogenicity population (for any serotype) included participants who were enrolled, received 20vPnC in the 20vPnC/saline group or received both vaccinations in the 13vPnC/PPSV23 group, had ≥1 valid OPA titers for any of the 7 additional serotypes from the blood collection 27-49 days after Vaccination 1 or 2 respectively, had no other major PDs.Number Analyzed=participants evaluable with OPA titers available at both timepoints at specified serotypes

The percentage of participants with a ≥4-fold rise in OPA titers and associated 95% CI before vaccination to 1 month after vaccination with 20vPnC or 13vPnC for the 13 matching serotypes, including 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F were summarized.

Participants Analyzed=Evaluable 13-matched immunogenicity population (for any serotype) included participants who were enrolled, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major PDs. Number Analyzed=participants evaluable with OPA titers available at both timepoints at specified serotype.

The percentage of participants with a ≥4-fold rise in OPA titers and associated 95% CI before vaccination to 1 month after vaccination with 20vPnC or PPSV23 for the 7 additional serotypes, including 8, 10A, 11A, 12F, 15B, 22F, and 33F were summarized.

Participants Analyzed=Evaluable 7-additional immunogenicity population (for any serotype): participants who were enrolled, received 20vPnC in the 20vPnC/saline group or received both vaccinations in the 13vPnC/PPSV23 group, had at least 1 valid OPA titers for any of the 7 additional serotypes from the blood collection 27 to 49 days after Vaccination 1 or 2 respectively, had no other major PDs. Number Analyzed=participants evaluable with OPA titers available at both timepoints at specified rows

The percentage of participants with OPA titers ≥LLOQ and associated 95% CIs were calculated for the time point 1 month after vaccination with 20vPnC or 13vPnC for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.

Participants Analyzed=Evaluable 13-matched immunogenicity population (for any serotype) included participants who were enrolled, received Vaccination 1 as randomized, had at least 1 valid OPA titer for any of the 13 matched serotypes from the blood collection 27 to 49 days after Vaccination 1, had no other major PDs. Number analyzed=participants evaluable for this OM at specified rows.

The percentage of participants with OPA titers ≥LLOQ and associated 95% CIs were calculated for the time point 1 month after vaccination with 20vPnC in the 20vPnC/saline groups or PPSV23 in the 13vPnC/PPSV23 group for serotypes: 8, 10A, 11A, 12F, 15B, 22F, and 33F.

Participants Analyzed=Evaluable 7-additional immunogenicity population (for any serotype): participants who were enrolled, received 20vPnC if randomized to 20vPnC/saline group or received both vaccinations if randomized to 13vPnC/PPSV23 group, had at least 1 valid OPA titers for any of the 7 additional serotypes from the blood collection 27 to 49 days after Vaccination 1 or Vaccination 2 respectively, had no other major PDs. Number analyzed=participants evaluable at specified rows.

Reactions within 10 days after Vaccination 2 (PPSV23 or saline) in participants enrolled at Japan sites were collected in the e-diary including redness, swelling, and pain at the injection site. Exact 2-sided CI was calculated based on the Clopper and Pearson method.

Redness and swelling were graded as mild (>2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), and severe (>10.0 cm).

Pain at the injection site was grades as mild (does not interfere with activity), moderate (interferes with activity), and severe (prevents daily activity).

This endpoint was requested by local Japan regulator.

Safety population included all participants enrolled at Japan sites who received at least 1 dose of the study intervention (20vPnC, 13vPnC, PPSV23 or saline) and had safety follow-up after any vaccination. Here, "Number of Participants Analyzed" is participants enrolled at Japan sites with any e-diary data reported after PPSV23 or saline.

Events within 7 days after Vaccination 2 (PPSV23 or saline) in participants enrolled at Japan sites were collected in the e-diary including fever, headache, fatigue, muscle pain, and joint pain. Exact 2-sided CI was calculated based on the Clopper and Pearson method.

Fever was categorized as ≥38.0 °C, ≥38.0°C to 38.4°C, >38.4°C to 38.9°C, >38.9°C to 40.0°C, and >40.0°C.

Fatigue, headache, muscle pain, and joint pain were grades as mild (does not interfere with activity), moderate (some interference with activity), and severe (prevents daily activity).

This endpoint was requested by local Japan regulator.

Safety population included all participants enrolled at Japan sites who received at least 1 dose of the study intervention (20vPnC, 13vPnC, PPSV23 or saline) and had safety follow-up after any vaccination. Here, "Number of Participants Analyzed" is participants enrolled at Japan sites with any e-diary data reported after PPSV23 or saline.