Vaxneuvance

Pharmaceutical Form: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is a suspension for injection available in 0.5 mL single-dose prefilled syringes.
Pharmaceutical Particulars: Chemistry: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is a sterile suspension of purified capsular polysaccharides from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F individually conjugated to CRM₁₉₇. Each pneumococcal capsular polysaccharide is activated via sodium metaperiodate oxidation and then individually conjugated to CRM₁₉₇ carrier protein via reductive amination. CRM₁₉₇ is a nontoxic mutant of diphtheria toxin (originating from Corynebacterium diphtheriae C7) expressed recombinantly in Pseudomonas fluorescens.
Each of the fifteen serotypes is manufactured independently using a common manufacturing platform with slight variations to accommodate for differences in strains, polysaccharides and process stream properties. The process consists of the fermentation steps to produce the inactivated pneumococcal bacteria and the purification process which consists of clarification, ultrafiltration, polishing and recovery to produce purified polysaccharides. Each activated polysaccharide is conjugated to lysine groups on the CRM₁₉₇ carrier protein using reductive amination. The pneumococcal polysaccharide powder is dissolved, size reduced to a target molecular mass, chemically activated, and buffer-exchanged by ultrafiltration. The CRM₁₉₇ protein carrier is then conjugated to the activated pneumococcal polysaccharide. The final vaccine is prepared by blending the fifteen conjugates with aluminum phosphate adjuvant in a final buffer containing histidine, polysorbate 20 and sodium chloride.
Composition: Active Ingredient: Each 0.5 mL dose contains 32 mcg of total pneumococcal polysaccharide (2.0 mcg each of polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F, and 4.0 mcg of polysaccharide serotype 6B) conjugated to 30 mcg of CRM₁₉₇ carrier protein.
Excipients/Inactive Ingredients: Each 0.5 mL dose contains 1.55 mg L-histidine, 1 mg of polysorbate 20, 4.50 mg sodium chloride, water for injection and 125 mcg of aluminum (as aluminum phosphate adjuvant).

Therapeutic Class: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is a conjugated polysaccharide vaccine that protects against invasive disease, pneumonia and acute otitis media caused by Streptococcus pneumoniae.
Pharmacology: Mechanism of Action: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) contains serotype-specific pneumococcal capsular polysaccharides, each of which is conjugated to a carrier protein (CRM₁₉₇), and elicits antibodies that enhance opsonization, phagocytosis, and killing of pneumococci to protect against pneumococcal disease. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicits a T-cell dependent immune response. Carrier protein-specific helper T-cells support specificity, functionality and maturation of serotype-specific B cells.
Immune responses following natural exposure to S. pneumoniae or following pneumococcal vaccination can be determined through the measurements of OPA and IgG responses. OPA represents functional antibodies capable of opsonizing pneumococcal capsular polysaccharides for presentation to phagocytic cells for engulfment and subsequent killing and are considered an important immunologic surrogate measure of protection against pneumococcal disease in adults. OPA titers are expressed as the reciprocal of the highest serum dilution that reduces survival of the pneumococci by at least 50%. Serotype-specific immune responses (OPA and IgG) for the 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were measured using a validated multiplexed opsonophagocytic assay (MOPA) and a validated pneumococcal electrochemiluminescence (Pn ECL) assay, bridged to the WHO reference enzyme linked immunosorbent assay (ELISA). In children, a serotype-specific IgG antibody level corresponding to ≥0.35 mcg/mL using the WHO ELISA has been used as the threshold value for the clinical evaluation of pneumococcal conjugate vaccines.
Clinical Studies: Burden of Disease: Pneumococcal disease is associated with significant morbidity and mortality in both children and adults worldwide. Although all age groups may be affected by pneumococcal disease, the highest rates of disease occur in young children <5 years of age and adults ≥65 years of age. Among children, the incidence of IPD and mortality associated with IPD is highest among infants <1 year of age. In addition, mortality rates are elevated in older adults, adults with comorbid conditions (e.g., diabetes mellitus, chronic lung disease, chronic liver disease), and especially in immunocompromised individuals (e.g., HIV infection, cancer, transplant, immunosuppressive therapies). Adults with 2 or more comorbid conditions may have a risk of pneumococcal disease that is comparable to that of immunocompromised individuals.
Clinical syndromes include both invasive pneumococcal disease (IPD) (i.e. sepsis, meningitis, and bacteremic pneumonia) and noninvasive disease (e.g., non-bacteremic pneumonia and acute otitis media). Bacteremic pneumococcal pneumonia represents approximately 80-90% of IPD cases in adults. Community acquired pneumonia (CAP) remains one of the most important causes of death from infection in many countries, with S. pneumoniae being one of the most commonly identified bacterial pathogens. Acute otitis media, a middle ear infection frequently caused by S. pneumoniae, is one of the most common infectious diseases of childhood and is a major cause of morbidity and antibiotic usage.
Clinical Studies: Clinical Trials Experience in Children 6 Weeks Through 17 Years of Age: Five double-blind, clinical studies (Protocol 008, Protocol 024, Protocol 025, Protocol 027, and Protocol 029) conducted across the Americas, Europe and Asia Pacific evaluated the immunogenicity of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in healthy infants, children and adolescents. In each study, immunogenicity was assessed by serotype-specific immunoglobulin G (IgG) response rates (the proportion of participants meeting the serotype-specific IgG threshold value of ≥0.35 mcg/mL) and IgG geometric mean concentrations (GMCs) at 30 days following the primary series and/or following the toddler dose. In a subset of participants, opsonophagocytic activity (OPA) geometric mean titers (GMTs) were also measured at 30 days following the primary series and/or following the toddler dose.
Infants and Toddlers Receiving a Routine Vaccination Schedule: 3-Dose Regimen: In a pivotal, double-blind, active comparator-controlled study (Protocol 025), 1,184 participants were randomized to receive Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 as a 3-dose regimen. The primary series was administered to infants at 2 and 4 months of age and the toddler dose was administered at 11 through 15 months of age. Participants also received other pediatric vaccines concomitantly, including Rotarix [rotavirus vaccine, live] with the infant primary series and INFANRIX hexa [diphtheria, tetanus, pertussis (acellular), hepatitis B (rDNA), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed)] with all 3 doses in the complete regimen [see Concomitant Vaccination].
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicits immune responses, as assessed by IgG response rates, IgG GMCs and OPA GMTs, for all 15 serotypes contained in the vaccine. At 30 days following the primary series, serotype-specific IgG response rates and IgG GMCs were generally comparable for the 13 shared serotypes and higher for the 2 unique serotypes (22F and 33F) in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) recipients, compared to Prevnar 13 recipients. At 30 days following the toddler dose, Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is non-inferior to Prevnar 13 for the 13 shared serotypes and superior for the 2 unique serotypes, as assessed by the proportion of participants meeting the serotype-specific IgG threshold value of ≥0.35 mcg/mL (response rate) (Table 1). Serotype-specific IgG GMCs are non-inferior to Prevnar 13 for the 13 shared serotypes and superior to Prevnar 13 for the 2 unique serotypes at 30 days following the toddler dose (Table 2). (See Tables 1 and 2.)

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Additionally, Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicits functional antibodies, as assessed by serotype-specific OPA GMTs at 30 days following the toddler dose, that are generally comparable to Prevnar 13 for the 13 shared serotypes. OPA GMTs for both 22F and 33F were higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) recipients compared to Prevnar 13 recipients.
4-Dose Regimen: In a double-blind, active comparator-controlled study (Protocol 008), 1,051 participants were randomized in a 1:1:1 ratio to receive one of two lots of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 as a 4-dose regimen. The primary series was administered to infants at 2, 4 and 6 months of age and the toddler dose was administered at 12 through 15 months of age. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) met non-inferiority criteria (the lower bound of the 2-sided 95% CI of the differences in the response rates [Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) - Prevnar 13] was greater than -15 percentage points) for the 13 shared serotypes as assessed by the serotype-specific IgG response rates at 30 days after the primary series. Serotype-specific IgG GMCs at 30 days following the primary series and 30 days following the toddler dose were generally comparable across both lots of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) and Prevnar 13 for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the 2 unique serotypes (22F and 33F).
In a pivotal, double-blind, active comparator-controlled study (Protocol 029), 1,720 participants were randomized to receive Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 as a 4-dose regimen. The primary series was administered to infants at 2, 4, and 6 months of age and the toddler dose was administered at 12 through 15 months of age. Participants also received other pediatric vaccines concomitantly, including RECOMBIVAX HB (Hepatitis B Vaccine [Recombinant]), RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent) and Pentacel (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate [Tetanus Toxoid Conjugate] Vaccine) in the infant primary series. HIBERIX (Haemophilus b Conjugate Vaccine [Tetanus Toxoid Conjugate]), M-M-R II (Measles, Mumps, and Rubella Virus Vaccine Live), VARIVAX (Varicella Virus Vaccine Live) and VAQTA (Hepatitis A Vaccine, Inactivated) were administered concomitantly with the toddler dose [see Concomitant Vaccination].
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicits immune responses, as assessed by IgG response rates, IgG GMCs and OPA GMTs for all 15 serotypes contained in the vaccine. At 30 days following the primary series, Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is non-inferior to Prevnar 13 for the 13 shared serotypes, as assessed by IgG response rates (Table 3). Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is non-inferior for the 2 unique serotypes, as assessed by the IgG response rates for serotypes 22F and 33F in recipients of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) compared with the response rate for serotype 23F in recipients of Prevnar 13 (the lowest response rate for any of the shared serotypes, excluding serotype 3), with percentage point differences of 6.7% (95% CI: 4.6, 9.2) and -4.5% (95% CI: -7.8, -1.3), respectively.
Additionally, Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is superior to Prevnar 13 for the 2 unique serotypes and for shared serotype 3 as assessed by IgG response rates at 30 days following the primary series (Table 3). (See Table 3.)

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At 30 days following the primary series, serotype-specific IgG GMCs are non-inferior to Prevnar 13 for 12 of the 13 shared serotypes. The IgG response to serotype 6A narrowly missed the prespecified non-inferiority criteria by a small margin (the lower bound of the 2-sided 95% CI for the GMC ratio [Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE)/Prevnar 13] being 0.48 versus >0.5) (Table 4). Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is non-inferior to Prevnar 13 for the 2 unique serotypes, as assessed by serotype-specific IgG GMCs for serotypes 22F and 33F in recipients of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) compared with the IgG GMC for serotype 4 in recipients of Prevnar 13 (the lowest IgG GMC for any of the shared serotypes, excluding serotype 3) with a GMC ratio of 3.64 (95% CI: 3.33, 3.98) and 1.24 (95% CI: 1.10, 1.39), respectively.
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is also superior to Prevnar 13 for the 2 unique serotypes and for shared serotype 3 as assessed by IgG GMCs at 30 days following the primary series (Table 4). (See Table 4.)

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At 30 days following the toddler dose, serotype-specific IgG GMCs for Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) are non-inferior to Prevnar 13 for all 13 shared serotypes and for the 2 unique serotypes as assessed by the IgG GMCs for serotypes 22F and 33F in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) recipients compared with the IgG GMC for serotype 4 in Prevnar 13 recipients (the lowest IgG GMC for any of the shared serotypes, excluding serotype 3) with a GMC ratio of 4.69 (95% CI: 4.30, 5.11) and 2.59 (95% CI: 2.36, 2.83), respectively (Table 5).
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is superior to Prevnar 13 for the 2 unique serotypes and for shared serotype 3, as assessed by IgG GMCs at 30 days following the toddler dose (Table 5). (See Table 5.)

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Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicits functional antibodies, as assessed by serotype-specific OPA GMTs at 30 days following the primary series and following the toddler dose, that are generally comparable to Prevnar 13 for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the 2 unique serotypes.
Infants and Toddlers Receiving a Mixed Dose Regimen of Different Pneumococcal Conjugate Vaccines: In a double-blind, active comparator-controlled, descriptive study (Protocol 027), 900 participants were randomized in a 1:1:1:1:1 ratio to one of five vaccination groups to receive a complete or mixed dosing regimen of pneumococcal conjugate vaccines. In two vaccination groups, participants received a 4-dose regimen of either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. In the three other vaccination groups, the vaccination series was initiated with Prevnar 13 and changed to Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) at Dose 2, Dose 3 or Dose 4. Participants also received other pediatric vaccines concomitantly, including RECOMBIVAX HB (Hepatitis B Vaccine [Recombinant]) and RotaTeq (Rotavirus Vaccine, Live, Oral, Pentavalent) [see Concomitant Vaccination]. Serotype-specific IgG GMCs at 30 days following the toddler dose were generally comparable for participants administered mixed regimens of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) and Prevnar 13 and for participants administered a complete dosing regimen of Prevnar 13 for the 13 shared serotypes, as assessed by IgG GMC ratios.
Infants, Children and Adolescents Receiving a Catch-Up Vaccination Schedule: In a double-blind, active comparator-controlled, descriptive study (Protocol 024), 606 participants were randomized to receive 1 to 3 doses of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13, depending on age at enrollment. Children who were either pneumococcal vaccine-naïve or not fully vaccinated or completed a dosing regimen with lower-valency pneumococcal conjugate vaccines were randomized into three different age cohorts (7 through 11 months of age, 12 through 23 months of age and 2 through 17 years of age), to receive 3, 2 or 1 dose of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 respectively, according to an age-appropriate schedule [see Dosage & Administration]. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicited serotype-specific immune responses, as assessed by IgG GMCs at 30 days following the last dose of vaccine within each age cohort, for all 15 serotypes contained in the vaccine. Catch-up vaccination with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicited immune responses in children 7 months through 17 years of age that are comparable to Prevnar 13 for the shared serotypes and higher than Prevnar 13 for the unique serotypes 22F and 33F. Within each age cohort, serotype-specific IgG GMCs at 30 days following the last dose of vaccine were generally comparable between the vaccination groups for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the 2 unique serotypes.
Clinical Trials Experience in Adults 18 Years of Age and Older: Six double-blind, clinical studies (Protocol 007, Protocol 016, Protocol 017, Protocol 019, Protocol 020 and Protocol 021) conducted across the Americas, Europe and Asia Pacific evaluated the immunogenicity of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in healthy and immunocompetent adults across different age groups including individuals with or without previous pneumococcal vaccination. The clinical studies included adults with stable underlying medical conditions (e.g., diabetes mellitus, renal disorders, chronic heart disease, chronic liver disease, chronic lung disease including asthma) and/or behavioral risk factors (e.g., smoking, increased alcohol use) that are known to increase the risk of pneumococcal disease.
In each study, immunogenicity was assessed by serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) responses at 30 days postvaccination. Study endpoints included OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs). The pivotal study (Protocol 019) was designed to show non-inferiority of the OPA GMTs compared to Prevnar 13 for the 13 shared serotypes (in common between Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) and Prevnar 13) and superiority for the 2 serotypes unique to Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) (22F and 33F) and for shared serotype 3. Superiority assessment was based on the between-group comparisons of OPA GMTs and proportions of participants with a ≥4-fold rise in serotype-specific OPA titers from prevaccination to 30 days postvaccination.
Clinical Trials Conducted in Pneumococcal Vaccine-Naïve Adults: In the pivotal, double-blind, active comparator-controlled study (Protocol 019), 1,205 pneumococcal vaccine-naïve adults aged 50 years or older were randomized to receive either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. The study demonstrated that Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is non-inferior to Prevnar 13 for the 13 shared serotypes and superior for the 2 unique serotypes and for shared serotype 3. Table 6 summarizes the OPA GMTs at 30 days postvaccination. Serotype-specific IgG GMCs were generally consistent with the results observed for the OPA GMTs. (See Table 6.)

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In a double-blind, lot consistency study (Protocol 020), 2,340 pneumococcal vaccine-naïve adults 50 years of age and older were randomized in a 3:3:3:1 ratio to receive 1 of 3 lots of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. The study demonstrated that all 3 lots are equivalent as the lower and upper limits of the 95% CI of the serotype-specific OPA GMT ratios between any 2 lots were within the equivalence margin (0.5 to 2.0) for all 15 serotypes. Immune responses following vaccination with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were comparable to Prevnar 13 for the shared serotypes.
In a double-blind, descriptive study (Protocol 017), 1,515 immunocompetent adults 18 to 49 years of age with or without risk factors for pneumococcal disease were randomized 3:1 to receive either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13, followed by PNEUMOVAX 23 six months later. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicited immune responses to all 15 serotypes as assessed by OPA GMTs (Table 7) and IgG GMCs. OPA GMTs and IgG GMCs were generally comparable between the two vaccination groups for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the 2 unique serotypes. Following vaccination with PNEUMOVAX 23, OPA GMTs and IgG GMCs were generally comparable between the two vaccination groups for all 15 serotypes in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).
Immune responses in adults with no risk factors (n=285; 25.2%) who received Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were generally consistent with those observed in the overall study population. (See Table 7.)

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Sequential Administration of Pneumococcal Vaccines in Adults: In a double-blind, active comparator-controlled study (Protocol 016), 652 pneumococcal vaccine-naïve adults 50 years of age and older were randomized to receive either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13, followed by PNEUMOVAX 23 one year later. Following vaccination with PNEUMOVAX 23, OPA GMTs and IgG GMCs were comparable between the two vaccination groups for all 15 serotypes in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).
Immune responses elicited by Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) persisted up to 12 months postvaccination as assessed by OPA GMTs and IgG GMCs. Immune responses at 30 days and 12 months postvaccination were comparable between the two vaccination groups for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the 2 unique serotypes.
The sequential administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) followed by PNEUMOVAX 23 was evaluated with an interval of 2 months in immunocompromised individuals (Protocol 018) and an interval of 6 months in immunocompetent individuals with or without risk factors for pneumococcal disease (Protocol 017). [See Use in Specific Populations under Precautions.]
Clinical Trials Conducted in Adults with Prior Pneumococcal Vaccination: In a double-blind, descriptive study (Protocol 007), 253 adults 65 years of age and older who were previously vaccinated with PNEUMOVAX 23 at least 1 year prior to study entry were randomized to receive either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. IgG GMCs and OPA GMTs were generally comparable between the vaccination groups for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the 2 unique serotypes.
Concomitant Vaccination: Infants and Toddlers: The immunogenicity of routine infant vaccines administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was evaluated within 3 double-blind, active comparator-controlled studies (Protocol 025, Protocol 029 and Protocol 027). In Protocol 025, approximately 1,200 participants received Rotarix concomitantly with the infant primary series and INFANRIX hexa concomitantly with the infant primary series and toddler dose of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. Immune responses to Rotarix administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) met non-inferiority criteria, as assessed by anti-rotavirus immunoglobulin A GMTs at 30 days following completion of the primary series. Similarly, immune responses to INFANRIX hexa administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) met non-inferiority criteria, as assessed by the antigen-specific response rate to each antigen in INFANRIX hexa at 30 days following the toddler dose.
In Protocol 029, approximately 1,700 participants received Pentacel administered concomitantly with the infant primary series of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. Approximately 1,500 participants received VAQTA, HIBERIX, M-M-R II and VARIVAX, administered concomitantly with the toddler dose of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. At 30 days following completion of the primary series, immune responses to all antigens contained in Pentacel met non-inferiority criteria when administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE). At 30 days following the toddler dose, immune responses to vaccine-specific antigens for VAQTA, HIBERIX, M-M-R II and VARIVAX met non-inferiority criteria when administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).
In Protocol 027, approximately 900 participants received RECOMBIVAX HB and RotaTeq concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 in the infant primary series. At 30 days following the primary series, immune responses to vaccine-specific antigens for RECOMBIVAX HB and RotaTeq met non-inferiority criteria when administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).
These studies support the concomitant administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) with any of the following vaccine antigens: diphtheria, tetanus, pertussis, poliomyelitis (serotypes 1, 2 and 3), hepatitis A, hepatitis B, Haemophilus influenzae type b, measles, mumps, rubella, varicella and rotavirus vaccine, either as monovalent or combination vaccines.
Adults: In a double-blind, randomized study (Protocol 021), 1,200 adults 50 years of age and older, with or without a history of prior Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) concomitantly or nonconcomitantly with seasonal inactivated quadrivalent influenza vaccine (QIV). One vaccination group received Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) and QIV concomitantly, followed by placebo 30 days later. A second vaccination group received QIV and placebo concomitantly, followed by Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) 30 days later.
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) administered concomitantly with QIV is non-inferior to Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) administered nonconcomitantly with QIV (based on a 2-fold non-inferiority margin), as assessed by pneumococcal OPA GMTs at 30 days postvaccination with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for all 15 serotypes contained in the vaccine. OPA GMTs were slightly lower for some serotypes when Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was administered concomitantly with QIV compared to Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) administered alone. QIV administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is non-inferior to QIV administered nonconcomitantly (based on a 2-fold non-inferiority margin) as assessed by influenza strain-specific hemagglutination inhibition (HAI) GMTs at 30 days postvaccination with QIV for all 4 influenza strains.
Toxicology: Repeat Dose Toxicity and Local Tolerance: Repeat-dose toxicity studies in rats at doses up to 17 times the infant human dose and up to 200 times the adult human dose on a mcg/kg basis, which included an evaluation of single-dose toxicity and local tolerance, revealed no hazards to humans.
Carcinogenesis: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) has not been evaluated for the potential to cause carcinogenicity.
Mutagenesis: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) has not been evaluated for the potential to cause genotoxicity.
Reproduction: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) administered to female rats at a dose approximately 200 times the adult human dose on a mcg/kg basis had no effects on mating performance, fertility or embryonic/fetal survival.
Development: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) administered to female rats at a dose approximately 200 times the adult human dose on a mcg/kg basis had no adverse effects on pre-weaning development. Antibodies to all 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were detected in offspring, attributable to the acquisition of maternal antibodies via placental transfer during gestation and possibly via lactation.

Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is a vaccine indicated in infants, children and adolescents from 6 weeks through 17 years of age (prior to the 18^th birthday) for active immunization for the prevention of invasive disease, pneumonia and acute otitis media caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F.
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is indicated in adults 18 years of age and older for active immunization for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F.
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) may not prevent disease caused by S. pneumoniae serotypes that are not contained in the vaccine.

General: The vaccination schedule for Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) should be based on official recommendations.
Dosage: Administer a 0.5 mL dose of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) intramuscularly.
Method of Administration: For intramuscular use only. Do not inject intravascularly.
The preferred site for injection is the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in children and adults. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk and/or blood vessel.
Pediatrics: Routine Vaccination Schedule for Infants and Toddlers: 3-Dose Regimen (Two-Dose Primary Series Followed by a Toddler Dose): The vaccination regimen consists of 3 doses of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE), with the first dose given as early as 6 to 12 weeks of age, and a second dose administered 8 weeks later. The third dose should be administered at approximately 11 through 15 months of age.
4-Dose Regimen (Three-Dose Primary Series Followed by a Toddler Dose): The vaccination regimen consists of 4 doses of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE), with the first dose given as early as 6 to 12 weeks of age, with an interval of 4 to 8 weeks between doses in the primary series. The fourth dose should be administered at approximately 11 through 15 months of age and at least 2 months after the third dose.
Preterm Infants: Preterm infants (<37 weeks gestation at birth) should receive a 4-dose regimen (three-dose primary series followed by a toddler dose) of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE), with the first dose given as early as 6 to 12 weeks of age, with an interval of 4 to 8 weeks between doses in the primary series. The fourth dose should be administered at approximately 11 through 15 months of age and at least 2 months after the third dose. [See Use in Specific Populations under Precautions.]
Prior Vaccination with Another Pneumococcal Conjugate Vaccine: The vaccination regimen can be completed with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) if initiated with another pneumococcal conjugate vaccine [see Pharmacology: Clinical Studies under Actions].
Catch-Up Vaccination Schedule for Children 7 Months Through 17 Years of Age: For children 7 months through 17 years of age who are pneumococcal vaccine-naïve or not fully vaccinated or completed a dosing regimen with lower-valency pneumococcal conjugate vaccines, the following catch-up schedule should be considered.
Infants 7 Through 11 months of age: Three doses, with the first two doses given at least 4 weeks apart. The third dose is given after 12 months of age, separated from the second dose by at least 2 months.
Children 12 Through 23 months of age: Two doses, with an interval of 2 months between doses.
Children and adolescents 2 Through 17 years of age: One single dose.
If a previous pneumococcal conjugate vaccine was administered, at least 2 months should elapse before receiving Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).
Adults: One single dose.

There are no data with regard to overdose.

Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is contraindicated in individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or any diphtheria toxoid-containing vaccine. [See Pharmaceutical Particulars under Description.]

Individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE). [See Interactions and Use in Specific Populations.]
The potential risk of apnea should be considered when administering any intramuscular vaccine to infants born prematurely. As the benefit of vaccination is high in this group of infants, vaccination generally should not be withheld or delayed.
As with any vaccine, Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) may not protect all vaccine recipients.
Use in Specific Populations: Individuals at Increased Risk for Pneumococcal Disease: Infants Born Prematurely: The safety and immunogenicity of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were evaluated in preterm infants (<37 weeks gestation at birth) enrolled within 4 double-blind, active comparator-controlled studies (Protocol 025, Protocol 027 [groups receiving a complete 4-dose regimen of either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 [Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM₁₉₇ Protein)]], Protocol 029 and Protocol 031). In these studies, 354 participants were randomized to receive Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 as a 4-dose regimen with the first dose administered at 2 months of age, followed by 2 additional doses at least 4 weeks apart and a fourth dose at 11 through 15 months of age. Serotype-specific immunoglobulin G (IgG) and opsonophagocytic activity (OPA) responses at 30 days following the primary series, prior to the toddler dose and at 30 days following the toddler dose were generally comparable between vaccination groups for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the two unique serotypes (22F and 33F). The safety profile and immune responses in preterm infants receiving 4 doses of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were generally consistent with those observed in the overall healthy infant population in these studies (including preterm and term infants) [see Adverse Reactions and Pharmacology: Clinical Studies under Actions].
Children with Sickle Cell Disease: In a double-blind, descriptive study (Protocol 023), the safety and immunogenicity of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were evaluated in children 5 to 17 years of age with sickle cell disease. In this study, 104 participants were randomized 2:1 to receive a single dose of either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was immunogenic as assessed by serotype-specific IgG GMCs and OPA GMTs at 30 days postvaccination for all 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE). Serotype-specific IgG GMCs and OPA GMTs were generally comparable between the two vaccination groups for the 13 shared serotypes and higher in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) for the two unique serotypes (22F and 33F). The safety profile of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in children with sickle cell disease was generally consistent with the safety profile in healthy children [see Adverse Reactions].
Individuals Living with HIV: Children Living with HIV: In a double-blind, descriptive study (Protocol 030), the safety and immunogenicity of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were evaluated in children 6 to 17 years of age living with HIV, with CD4+ T-cell count ≥200 cells per microliter and plasma HIV RNA value <50,000 copies/mL. In this study, 407 participants were randomized to receive a single dose of either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13, followed by PNEUMOVAX 23 [pneumococcal vaccine polyvalent] two months later. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was immunogenic as assessed by serotype-specific IgG GMCs and OPA GMTs at 30 days postvaccination for all 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE). Serotype-specific IgG GMCs and OPA GMTs were generally comparable for the 13 shared serotypes and higher for the 2 unique serotypes (22F and 33F). After sequential administration with PNEUMOVAX 23, IgG GMCs and OPA GMTs were generally comparable at 30 days postvaccination between the two vaccination groups for all 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE). The safety profile of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in children living with HIV was generally consistent with the safety profile in healthy children [see Adverse Reactions].
Adults Living with HIV: In a double-blind, descriptive study (Protocol 018), the safety and immunogenicity of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were evaluated in pneumococcal vaccine-naïve adults ≥18 years of age living with HIV, with CD4+ T-cell count ≥50 cells per microliter and plasma HIV RNA value <50,000 copies/mL. In this study, 302 participants were randomized to receive either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13, followed by PNEUMOVAX 23 two months later. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was immunogenic as assessed by OPA GMTs and IgG GMCs at 30 days postvaccination for all 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE). After sequential administration with PNEUMOVAX 23, OPA GMTs and IgG GMCs were generally comparable at 30 days postvaccination between the two vaccination groups for all 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE). The safety profile of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in adults living with HIV was generally consistent with the safety profile in immunocompetent pneumococcal vaccine-naïve adults [see Adverse Reactions].
Individuals 18 to 49 Years of Age with Chronic Conditions and Other Risk Factors: In a double-blind, descriptive study (Protocol 017), the safety and immunogenicity of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were evaluated in immunocompetent adults 18 to 49 years of age, including individuals with one or more of the following risk factors for pneumococcal disease: diabetes mellitus, chronic heart disease including heart failure, chronic liver disease with compensated cirrhosis, chronic lung disease including persistent asthma and chronic obstructive pulmonary disease (COPD), current tobacco use and increased alcohol consumption. Participants were randomized 3:1 to receive either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13, followed by PNEUMOVAX 23 six months later. Of those who received Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE), 54.7% (n=620) had 1 risk factor and 20.1% (n=228) had 2 or more risk factors. In both of these risk factor subgroups, Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) elicited immune responses to all 15 serotypes contained in the vaccine as assessed by OPA GMTs and IgG GMCs at 30 days postvaccination, which were generally consistent with those observed in the overall study population [see Pharmacology: Clinical Studies under Actions]. Sequential administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) followed by PNEUMOVAX 23 was also immunogenic for all 15 serotypes. The safety profile of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in both of these risk factor subgroups was generally consistent with the safety profile in the overall study population [see Adverse Reactions].
Use in Children: The safety and effectiveness of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in children younger than 6 weeks of age have not been established.
Use in the Elderly: Of the 4,344 individuals aged 50 years and older who received Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE), 2,470 (56.9%) were 65 years and older, and 479 (11.0%) were 75 years and older [see Adverse Reactions and Pharmacology: Clinical Studies under Actions].

Pregnancy: Animal Data: Developmental and reproductive toxicity studies have been performed in female rats at a dose approximately 200 times the adult human dose on a mcg/kg basis. In these studies, female rats received Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) (32 mcg/rat/dose) by intramuscular injection 28 days and 7 days prior to mating, on gestation day 6 and on lactation day 7. There was no evidence of embryofetal lethality or fetal malformations and variations and no adverse effects on pre-weaning development were observed. Antibodies to all 15 serotypes contained in Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) were detected in offspring, attributable to the acquisition of maternal antibodies via placental transfer during gestation and possibly via lactation.
Human Data: There are no adequate and well-controlled studies of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in pregnant women, and human data available from clinical trials with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) have not established the presence or absence of vaccine-associated risk during pregnancy. The decision to vaccinate a woman who is pregnant should consider the woman's risk of pneumococcal disease; Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) should be administered only if clearly needed.
Nursing Mothers: It is not known whether this vaccine is excreted in human milk.

Clinical Trials Experience: Children 6 Weeks Through 17 Years of Age: Infants and Toddlers Receiving a Routine Vaccination Schedule: The safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in healthy infants (from 6 weeks of age at first vaccination) and toddlers (11 months through 15 months of age) was assessed in 5 randomized, double-blind, active comparator-controlled clinical studies (Protocol 008, Protocol 025, Protocol 027, Protocol 029 and Protocol 031) of 7,229 participants conducted across the Americas, Europe, and Asia Pacific. In four of these studies (Protocol 008, Protocol 027, Protocol 029 and Protocol 031), the safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was evaluated when administered as a 4-dose regimen given at 2, 4, 6 and 12 through 15 months of age. A fifth study (Protocol 025) evaluated the safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) when administered as a 3-dose regimen given at 2, 4 and 11 through 15 months of age. All 5 studies evaluated the safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) when administered concomitantly with other routine pediatric vaccinations [see Pharmacology: Clinical Studies under Actions]. Protocol 027 also evaluated the safety of mixed 4-dose regimens in participants who completed the regimen with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) after receiving one or more doses of Prevnar 13. Additionally, four of these studies evaluated safety in preterm infants (<37 weeks gestation at birth) [see Use in Specific Populations under Precautions]. Across all 5 studies, 4,286 participants received a complete regimen of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE), 2,405 participants received a complete regimen of Prevnar 13 and 538 participants received a mixed regimen.
Safety was evaluated using a Vaccination Report Card for up to 14 days postvaccination. Injection-site adverse events and systemic adverse events were solicited on Day 1 through Day 14 postvaccination. Body temperature was solicited on Day 1 through Day 7 postvaccination. Unsolicited adverse events were reported on Day 1 through Day 14 postvaccination. The duration of the safety follow-up period following the last vaccination with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was 1 month in Protocol 008 and 6 months in Protocol 025, Protocol 027, Protocol 029 and Protocol 031.
Solicited Adverse Reactions in Infants and Toddlers Receiving a Routine Vaccination Schedule: The percentage of infants (preterm and term) and toddlers with solicited adverse reactions that occurred within 14 days following administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 based on pooled data from four studies (excluding mixed 4-dose regimens) are shown in Tables 8 and 9. The majority of solicited adverse reactions were mild to moderate (based on intensity or size) and of short duration (≤3 days). Severe reactions (defined as being extremely distressed or unable to do usual activities or size >7.6 cm) occurred in ≤1.3% of infants and toddlers following each dose, with the exception of irritability, which occurred in ≤5.2% of the participants. (See Tables 8 and 9.)

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Unsolicited Adverse Reactions in Infants and Toddlers Receiving a Routine Vaccination Schedule: Injection-site urticaria occurred in up to 0.3% of infants and toddlers following each dose of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).
Safety with Concomitant Administration in Infants and Toddlers: The safety profile was similar when other routine pediatric vaccines were administered concomitantly with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 [see Pharmacology: Clinical Studies under Actions].
Safety of a Mixed Dose Regimen of Different Pneumococcal Conjugate Vaccines: The safety profiles of mixed 4-dose regimens of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) and Prevnar 13 were generally comparable to those of complete 4-dose regimens of either Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 [see Pharmacology: Clinical Studies under Actions].
Infants, Children and Adolescents Receiving a Catch-Up Vaccination Schedule: The safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in healthy infants, children and adolescents from 7 months through 17 years of age was assessed in a double-blind, active comparator-controlled clinical study (Protocol 024) in which 606 participants were randomized to receive 1 to 3 doses of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13, depending on age at enrollment. All infants and children less than 2 years of age were pneumococcal vaccine-naïve. Among children and adolescents from 2 through 17 years of age (N=352), 42.9% had a history of previous vaccination with a lower-valency pneumococcal conjugate vaccine. The safety assessment was consistent with that used in the studies evaluating a routine vaccination schedule. The duration of the safety follow-up period following the last study vaccination within each age cohort was 6 months.
Solicited Adverse Reactions in Infants, Children and Adolescents Receiving a Catch-Up Vaccination Schedule: The percentage of participants with solicited adverse reactions that occurred within 14 days following administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 within each age cohort are shown in Tables 10, 11 and 12. The majority of solicited adverse reactions were mild to moderate (based on intensity or size) and of short duration (≤3 days). Severe reactions (defined as being extremely distressed or unable to do usual activities or size >7.6 cm) occurred in ≤1.6% of infants and children 7 months through 23 months of age following each dose, and ≤4.5% of children and adolescents 2 through 17 years of age. (See Tables 10, 11 and 12.)

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Adults 18 Years of Age and Older: The safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in healthy and immunocompetent adults was assessed in 6 randomized, double-blind clinical studies (Protocol 007, Protocol 016, Protocol 017, Protocol 019, Protocol 020 and Protocol 021) conducted across the Americas, Europe and Asia Pacific, which included 7,136 adults ranging in age from 18 to 98 years. Each study enrolled adults with stable underlying medical conditions and/or risk factors that are known to increase the risk of pneumococcal disease.
Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was administered to 5,478 adults; 1,134 were 18 to 49 years of age, 1,874 were 50 to 64 years of age, and 2,470 were 65 years of age and older. Of those who received Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE), 5,101 adults were pneumococcal vaccine-naïve and 377 adults were previously vaccinated with PNEUMOVAX 23 at least 1 year prior to enrollment.
The safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in pneumococcal vaccine-naïve adults 50 years of age and older was evaluated in 3 active comparator-controlled clinical studies (Protocol 016, Protocol 019 and Protocol 020) in which 3,032 participants received Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) and 1,154 participants received Prevnar 13 (PCV13). A descriptive study (Protocol 017) evaluated the safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in pneumococcal vaccine-naïve adults 18 to 49 years of age.
The safety of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) in adults 65 years of age and older who were previously vaccinated with PNEUMOVAX 23 (at least 1 year prior to study entry) was evaluated in an additional descriptive study (Protocol 007).
The safety of concomitant administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) with seasonal inactivated influenza vaccine was evaluated in 1,196 adults 50 years of age and older, including those with or without a history of prior vaccination with PNEUMOVAX 23 (Protocol 021).
Safety was evaluated using a Vaccination Report Card for up to 14 days postvaccination. Oral body temperature and injection-site adverse events were solicited on Day 1 through Day 5 postvaccination. Systemic adverse events were solicited on Day 1 through Day 14 postvaccination. Unsolicited adverse events were reported on Day 1 through Day 14 postvaccination. The duration of the safety follow-up period postvaccination with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) was 1 month in Protocol 007, 6 months in Protocol 019, Protocol 020, Protocol 017 and Protocol 021 and 12 months in Protocol 016.
Solicited Adverse Reactions: The percentage of participants with solicited adverse reactions that occurred within 5 or 14 days following administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) or Prevnar 13 in 5 studies are shown in Tables 13 and 14. All solicited adverse reactions occurred in ≥5% of participants with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE); older adults reported fewer solicited adverse reactions than younger adults, regardless of vaccination group. The majority of solicited adverse reactions were mild (based on intensity or size) and of short duration (≤3 days); severe reactions (defined as an event that prevents normal daily activity or size >10 cm) occurred in ≤1.5% of adults. (See Tables 13 and 14.)

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Unsolicited Adverse Reactions: Injection-site pruritus occurred in 1.0% to 2.8% of pneumococcal vaccine-naïve adults vaccinated with Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).
Safety with Concomitant Influenza Vaccine Administration: The safety profile of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) when administered concomitantly with inactivated influenza vaccine was generally consistent with the safety profile of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE).

Use with Other Vaccines: Infants and Children Less Than 2 Years of Age: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) can be administered concomitantly with other routine pediatric vaccines [see Adverse Reactions and Pharmacology: Clinical Studies under Actions].
Children and Adolescents 2 Through 17 Years of Age: There are no data on the concomitant administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) with other vaccines.
Adults: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) can be administered concomitantly with inactivated influenza vaccine [see Adverse Reactions and Pharmacology: Clinical Studies under Actions]. There are no data on the concomitant administration of Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) with other vaccines.
Use with Immunosuppressive Therapies: Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids, therapeutic proteins and targeted immunomodulators may reduce the immune responses to vaccines [see Precautions].

Instructions for Use: Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) should not be diluted or mixed with other vaccines. The full recommended dose of the vaccine should be used.
When Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is administered at the same time as another injectable vaccine(s), the vaccines should always be given at different injection sites [see Interactions].
Because this product is a suspension containing an adjuvant, hold horizontally and shake vigorously immediately prior to use to obtain an opalescent suspension in the vaccine container. Do not use the vaccine if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. This product should not be used if particulate matter or discoloration is found.
The prefilled syringe is for single use only and should not be used for more than one individual. Attach a needle by twisting in a clockwise direction until the needle fits securely on the syringe. Inject the entire contents of the syringe. Exercise caution to avoid harm from an accidental needle stick.

Store at temperatures between 2-8°C. Do not freeze. Protect from light. Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) should be administered as soon as possible after being removed from the refrigerator.
In the event of temporary temperature excursions, stability data indicate that Pneumococcal Polysaccharide Conjugate Vaccine, 15-Valent (Adsorbed) (VAXNEUVANCE) is stable at temperatures up to 25°C for 48 hours.

Vaccines, Antisera & Immunologicals

J07AL02 - pneumococcus, purified polysaccharides antigen conjugated ; Belongs to the class of pneumococcal bacterial vaccines.

Rx