A Phase 3, Multicenter, Randomized, Double-blind, Active Comparatorcontrolled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by Administration of PNEUMOVAX™23 Six Months Later in Immunocompetent Adults Between 18 and 49 Years of Age at Increased Risk for Pneumococcal Disease (PNEU – DAY)

INTERVENTION: Product Name: 15‐Valent Pneumococcal Conjugate Vaccine Product Code: V114 Pharmaceutical Form: Suspension for injection in pre‐filled syringe INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1 CONJUGATED TO CRM197 Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1 CONJUGATED TO CRM197 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 2‐ INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3 CONJUGATED TO CRM197 Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3 CONJUGATED TO CRM197 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 2‐ INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4 CONJUGATED TO CRM197 Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4 CONJUGATED TO CRM197 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 2‐ INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5 CONJUGATED TO CRM197 Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5 CONJUGATED TO CRM197 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 2‐ INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A CONJUGATED TO CRM197 Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A CONJUGATED TO CRM197 Concentration unit: µg microgram(s) Concentration CONDITION: Pneumococcal disease ; MedDRA version: 20.0 Level: PT Classification code 10061353 Term: Pneumococcal infection System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] SECONDARY OUTCOME: ; Secondary end point(s): 1) Serotype‐specific IgG GMCs at 30 days postvaccination with V114 and Prevnar 13â„¢ (Day 30) ; 2) Serotype‐specific OPA GMTs and IgG GMCs at 30 days postvaccination with PNEUMOVAXâ„¢23 (Month 7) ; 3) Proportion of participants with solicited injection‐site AEs (redness/erythema, swelling, tenderness/pain) from Day 1 through Day 5 following PNEUMOVAXâ„¢23 ; 4) Proportion of participants with solicited systemic AEs (muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue) from Day 1 through Day 14 following PNEUMOVAXâ„¢23 ; 5) Proportion of participants with vaccine‐related SAEs in the 30 days following PNEUMOVAXâ„¢23 from Month 6 through Month 7; ; Timepoint(s) of evaluation of this end point: Day 1 through Day 5 postvaccination of PNEUMOVAXâ„¢23, Day 1 through Day 14 postvaccination of PNEUMOVAXâ„¢23, ; Month 6 to Month 7, Day 1, Day 30, Month 6, Month 7; INCLUSION CRITERIA: 1. Native American from clinical sites of the CAIH in good health without any of the risk conditions for pneumococcal disease listed below (any underlying chronic illness must be documented to be in stable condition); OR Native American from clinical sites of the CAIH OR a participant from sites other than the CAIH with =1 of the following risk conditions for pneumococcal disease: a. Diabetes mellitus Type 1 or Type 2, receiving treatment with at least 1 approved antidiabetic medication; with hemoglobin A1c (HgA1c) <10% at Screening (Visit 1) i. Prior liver biopsy demons PRIMARY OUTCOME: ; Main Objective: 1) To evaluate the safety and tolerability of V114 and Prevnar 13â„¢ with respect to the proportion of participants with adverse events (AEs) within each vaccination group separately; 2) To evaluate the serotype‐specific opsonophagocytic activity (OPA) Geometric Mean Titers (GMTs) at 30 days postvaccination (Day 30) with V114 and Prevnar 13â„¢ within each vaccination group separately; ; Primary end point(s): 1) The serotype‐specific OPA GMTs at 30 days postvaccination with V114 and Prevnar 13â„¢ (Day 30); 2) Proportion of participants with solicited injection‐site AEs (redness/erythema, swelling, tenderness/pain) from Day 1 through Day 5 following V114 or Prevnar 13â„¢; 3) Proportion of participants with solicited systemic AEs (muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue) from Day 1 through Day 14 following V114 or Prevnar 13â„¢; 4) Proportion of participants with vaccine‐related SAEs in the 6 months following V114 or Prevnar 13â„¢ from Day 1 through Month 6; ; Secondary Objective: ‐PNEUMOVAX Safety,tolerability administered 6 months following V114 and Prevnar13 with respect to the proportion of AEs within each group separately; ‐Serotype‐specific ImmunoglobulinG(IgG)Geometric Mean Concentrations(GMCs) at30 days postvaccination withV114 and Prevnar13 within each group separately; ‐Serotype‐specific Geometric Mean Fold Rises(GMFRs), proportions of subjects with =4‐fold rise from prevaccination to30 days postvaccination withV114 and Prevnar13 for both OPA and IgG responses within each group separately; ‐The serotype‐specific(1)OPA GMTs,IgG GMCs at30 days postvaccination with PNEUMOVAX,(2)GMFRs, proportions of subjects with =4‐fold rise from prevaccination to30 days postvaccination with PNEUMOVAX for both OPA and IgG responses,(3)GMFRs,proportions of subjects with =4‐fold rise from prevaccination with PNEUMOVAX to30 days postvaccination with PNEUMOVAX for both OPA and IgG responses for subjects administered V114 and separately Prevnar13 6 months before PNEUMOVAX; Timepoint(s) of evaluation of this end point: Day 1 through Day 5 postvaccination of V114 or Prevnar 13â„¢, Day 1 through Day 14 postvaccination of V114 or Prevnar 13â„¢, Day 1 to Month 6, Day 30 b. Chronic liver disease with compensated cirrhosis (Child‐Pugh Class A) due to nonalcoholic fatty liver disease, chronic hepatitis B, chronic hepatitis C, or alcoholic liver disease, diagnosed by clinician’s assessment, with at least 1 of the following liver staging assessments: