Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine manufactured with and without polysorbate 80 given to healthy infants at 2, 3, 4 and 12 months of age.

BACKGROUND: Polysorbate 80 (P80), a nonionic detergent used to solubilize proteins, is used in both oral and injectable medications including vaccines. Development studies with 13-valent pneumococcal conjugate vaccine (PCV13) showed that adding P80 resulted in a more robust manufacturing process. Before adding P80 to the formulation of PCV13, we investigated the immunogenicity and safety of PCV13 with and without P80. METHODS: Phase 3, parallel-group, randomized, active-controlled, double-blind multicenter trial was conducted at 15 sites in Poland. Healthy infants were randomized (1:1) to receive PCV13+P80 or PCV13 without P80 given at ages 2, 3, 4 and 12 months concomitantly with DTaP-IPV-Hib at 2, 3 and 4 months; hepatitis B at 2 months and measles, mumps, and rubella at 12 months. Serotype-specific antipneumococcal immune responses were evaluated using antipolysaccharide capsular immunoglobulin (Ig)G responses and opsonophagocytic activity (OPA) assay. Safety data were also collected. RESULTS: The 2 treatment groups were demographically similar. Following the infant immunization series, anticapsular IgG antibody geometric mean concentrations and OPA geometric mean titers for each serotype were within 2-fold between the 2 groups. Formal noninferiority criteria for comparison of proportion of responders (subjects with IgG titers ≥0.35 µg/mL) were met for 11 of the 13 serotypes. Overall population responses were highly similar. Anticapsular IgG responses were also within 2-fold following the toddler dose. Safety profiles were similar between the 2 groups. CONCLUSIONS: Addition of P80 to PCV13 did not adversely affect PCV13 immunogenicity or safety when compared with vaccine formulated without P80.

NIHR Medicines for Children Research Network: improving children's health through clinical research.

The need to evaluate medicines for children is widely acknowledged due to pervasive unlicensed medicine use in the pediatric setting. The EU Paediatric Regulation was developed to address these considerations, which subsequently led to the establishment of the National Institute of Health Research (NIHR) Medicines for Children Research Network (MCRN) in England. MCRN supports public and industry studies, and facilitates feasibility, site setup, recruitment and other services. The MCRN and other networks are members of the European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA). Enpr-EMA was established to foster and coordinate research, and develop collaborations across Europe. MCRN works with Enpr-EMA, industry and others to improve the conduct of research for the benefit of children's health.

13-Valent pneumococcal conjugate vaccine (PCV13) in children partially immunized with 7-valent pneumococcal conjugate vaccine (PCV7): a phase 3, open-label trial.

BACKGROUND: As 13-valent pneumococcal conjugate vaccine (PCV13) is introduced, children who began vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) may complete their vaccination with PCV13. This open-label phase 3 study evaluated immunogenicity and safety of PCV13 in Swedish infants and toddlers previously given 1 or 2 doses of PCV7 during infancy. METHODS: Healthy infants previously given PCV7 at ages 3 months (group 1; n=118) or 3 and 5 months (group 2; n=116) received PCV13 at ages 5 (group 1) and 12 months (both groups). IgG responses were assessed 1 month after each PCV13 dose and before the 12-month dose. Local reactions and systemic events were collected for 7 days postvaccination. Other adverse events were also collected. RESULTS: Post-5-month dose, IgG geometric mean concentrations (GMCs) in group 1 were 1.56-4.70 µg/ml for most PCV7 serotypes except 6B (0.40 µg/ml) and 23F (0.57 µg/ml) and 0.72-1.88 µg/ml for most of the 6 additional serotypes, except 6A (0.28 µg/ml). Post-12-month dose, IgG GMCs for the PCV7 serotypes were 2.93-9.63 µg/ml (group 1) and 3.33-9.30 µg/ml (group 2); and for the 6 additional serotypes, 1.85-14.65 µg/ml (group 1) and 1.34-13.16 µg/ml (group 2). GMCs increased by >4-fold in both groups from pre- to post-12-month dose. Proportions of subjects in group 1 with pneumococcal serotype-specific IgG concentrations ≥0.35 µg/ml (WHO-designated postprimary reference antibody level) post-5-month dose were 92.2-99.1% for most PCV7 serotypes except 6B (53.0%) and 23F (62.6%) and 80.9-100.0% for most of the 6 additional serotypes except 6A (36.8%). Local reactions and fever were mostly mild or moderate. CONCLUSIONS: PCV13 was immunogenic and safe in infants and toddlers previously partially immunized with PCV7. Even a single dose in an infant or toddler induces an immune response to the 6 additional serotypes.

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in healthy infants and toddlers given with routine vaccines in India.

BACKGROUND: The childhood burden of disease attributable to Streptococcus pneumoniae is particularly high in India. The immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) were compared with 7-valent pneumococcal conjugate vaccine (PCV7) in a randomized, active-controlled, double-blind trial conducted at 12 sites in India. METHODS: Healthy infants received PCV13 or PCV7 at 6, 10, and 14 weeks of age (infant series) and at 12 months of age (toddler dose), along with routine pediatric vaccinations. Immunoglobulin G responses against the 13 pneumococcal serotypes were evaluated 1 month after the infant series and after the toddler dose. Pertussis and poliomyelitis immune responses were assessed 1 month after the infant series. Safety and tolerability also were assessed. RESULTS: The immunogenicity results for the 7 common serotypes and the concomitant vaccines (whole-cell pertussis and oral poliovirus) were similar for subjects receiving PCV13 and subjects receiving PCV7. Immune responses to the 6 additional serotypes were higher in the PCV13 group compared with the PCV7 group. PCV13 and PCV7 had similar safety and tolerability profiles. CONCLUSIONS: PCV13 has immunogenicity similar to PCV7 in response to the 7 common serotypes, and has generally higher immunogenicity in response to the 6 additional serotypes. PCV13 may provide added protection against pneumococcal disease caused by the additional 6 serotypes and does not interfere with immune responses to whole-cell pertussis and oral poliovirus vaccines. PCV13 has an acceptable safety profile in both infants and toddlers, comparable with that of PCV7.

Phase 3 trial evaluating the immunogenicity, safety, and tolerability of manufacturing scale 13-valent pneumococcal conjugate vaccine.

13-valent pneumococcal conjugate vaccine (PCV13) includes polysaccharide conjugates from six pneumococcal serotypes in addition to those in the licensed 7-valent vaccine, thereby offering expanded protection against pneumococcal disease. The phase 3 trial reported here was conducted per a regulatory requirement to evaluate the immunogenicity, safety, and tolerability of two lots of the final PCV13 formulation that differed with respect to production scale but not the manufacturing process. The anti-pneumococcal polysaccharide immunogenicity and safety/tolerability were found to be similar between the two PCV13 vaccine lots.

Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine compared to those of a 7-valent pneumococcal conjugate vaccine given as a three-dose series with routine vaccines in healthy infants and toddlers.

A 13-valent pneumococcal conjugate vaccine (PCV13) has been developed to improve protection against pneumococcal disease beyond that possible with the licensed 7-valent vaccine (PCV7). This study compared the safety and immunogenicity of PCV13 with those of PCV7 when given as part of the pediatric vaccination schedule recommended in Italy. A total of 606 subjects were randomly assigned to receive either PCV13 or PCV7 at 3, 5, and 11 months of age; all subjects concomitantly received diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B (DTaP-HBV-IPV/Hib) vaccine. Vaccine reactions were monitored. Antibody responses to DTaP-HBV-IPV/Hib antigens, serotype-specific anticapsular polysaccharide IgG responses, and antipneumococcal opsonophagocytic assay (OPA) activity were measured 1 month after the two-dose primary series and 1 month after the toddler dose. Overall, the safety profile of PCV13 was similar to that of PCV7. The response to DTaP-HBV-IPV/Hib antigens was substantially the same with both PCV13 and PCV7. PCV13 elicited antipneumococcal capsular IgG antibodies to all 13 vaccine serotypes, with notable increases in concentrations seen after the toddler dose. Despite a lower immunogenicity for serotypes 6B and 23F after the primary series of PCV13, responses to the seven common serotypes were comparable between the PCV13 and PCV7 groups when measured after the toddler dose. PCV13 also elicited substantial levels of OPA activity against all 13 serotypes following both the infant series and the toddler dose. In conclusion, PCV13 appeared comparable to PCV7 in safety profile and immunogenicity for common serotypes, demonstrated functional OPA responses for all 13 serotypes, and did not interfere with immune responses to concomitantly administered DTaP-HBV-IPV/Hib vaccine.

Immunogenicity and reactogenicity of a 13-valent-pneumococcal conjugate vaccine administered at 2, 4, and 12 months of age: a double-blind randomized active-controlled trial.

BACKGROUND: A 2-, 4-, and 12-month schedule of a novel 13-valent-pneumococcal conjugate vaccine (PCV13), containing serotype 1, 3, 4, 5, 6A, 6B 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharides individually conjugated to CRM197 was evaluated in a randomized, double-blind, controlled infant study. METHODS: Two hundred eighty-six healthy infants received PCV13 or the 7-valent-pneumococcal conjugate vaccine (PCV7) at 2, 4, and 12 months of age, alongside a serogroup C meningococcal (MenC) vaccine (2 and 4 months of age), DTaP-IPV-Hib (2, 3, and 4 months), and a Hib-MenC vaccine (12 months). Specific antibody responses were assessed at age 5, 12, and 13 months. RESULTS: At 13 months of age, >97% of PCV13 recipients had pneumococcal serotype-specific serum IgG concentrations ≥0.35 µg/mL for each vaccine serotype except serotype 3 (88.2%), and at least 93% of PCV13 recipients had OPA titers ≥1:8 for each serotype. At 5 months, 110/114 (96.5%) of PCV13 recipients and 100/102 (98.0%) of PCV7 recipients had serum anti-PRP (Hib) IgG concentration ≥0.15 µg/mL (difference, 1.5%; CI, -7.1%­3.7%), while 119/120 (99.2%) and 117/118 (99.2%), respectively, had MenC serum bactericidal assay titers of ≥1:8. All PCV13 recipients and 110/113 (97.3%) of PCV7 recipients had IgG concentrations against fimbrial agglutinogens of ≥2.2 EU/mL; IgG concentrations for the remaining pertussis antigens were ≥5 EU/mL for all participants. Local reactions and systemic events were similar in the PCV13 and PCV7 groups. CONCLUSIONS: A 2-, 4-, and 12-month course of PCV13 was immunogenic for all 13 vaccine serotypes and was well tolerated.