Safety, tolerability, and immunologic noninferiority of a 13-valent pneumococcal conjugate vaccine compared to a 7-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in Germany

Kieninger, Dorothee; Kueper, Kathrin; Steul, Katrin; Juergens, Christine; Ahlers, Norbert; Baker, Sherryl; Jansen, Kathrin U.; Devlin, Carmel; Gruber, William C.; Emini, Emilio A.; Scott, Daniel A.

doi:10.1016/j.vaccine.2010.04.008

Cited by 165 publications

(117 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This unique response pattern observed for serotype 3 is consistent with findings from other studies. 19,20 Despite this observed phenomenon, studies of early vaccine effectiveness suggest that disease protection is afforded by direct vaccination against serotype 3. 21,22 Although several methodologic differences exist when comparing this study with previous studies of GMR, geometric mean ratio.…”

Section: E880mentioning

confidence: 99%

13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Preterm Versus Term Infants

et al. 2015

Self Cite

View full text Add to dashboard Cite

OBJECTIVES: This study evaluated the immune response and safety profile of 13-valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with term infants.METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel-group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged 42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and 12 (toddler dose [TD]) months, together with routine vaccines (diphtheriatetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine and meningococcal group C conjugate vaccine).RESULTS: Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody concentration $0.35 mg/mL for all serotypes: .85% after the infant series (except preterm infants for serotypes 5, 6A, and 6B) and .97% after TD (except for serotype 3). Preterm infants had overall lower IgG geometric mean concentrations compared with term infants; however, geometric mean fold increases after TD were similar for all serotypes. Opsonophagocytic activity results were consistent with IgG results and titers increased after TD in both groups for all serotypes, including serotype 3. PCV13 was generally well tolerated, with similar safety profiles in all preterm subgroups.CONCLUSIONS: Immune responses were lower in preterm infants than in term infants. However, the majority of subjects in both groups achieved both pneumococcal serotype-specific IgG antibody levels after the infant series that exceeded the World Health Organization-established threshold of protection and functional antibody responses. Responses were uniformly higher after TD, reinforcing the importance of a timely booster dose. PCV13 was well tolerated regardless of gestational age.

show abstract

Section: E880mentioning

confidence: 99%

13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Preterm Versus Term Infants

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the net vaccine benefit has been negatively affected by a 71% increased rate of invasive pneumococcal disease caused by nonvaccine serotypes (30). Recently, a 13-valent pneumococ-cal conjugate vaccine (PCV-13) was developed to further improve protection (9,19) by covering the serotypes that most frequently cause infection and colonization. However, the increase in carriage of nonvaccine serotypes, and the associated increase in invasive disease, could ultimately outweigh the benefits of the current PCV (21).…”

mentioning

confidence: 99%

Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study

et al. 2011

View full text Add to dashboard Cite

The currently available pneumococcal vaccines do not protect against all serotypes of Streptococcus pneumoniae. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (n ‫؍‬ 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.

show abstract

“…(30)(31)(32)(33) In both pivotal studies, the ELISA response to 6B was inferior in PNEU-C-13 as compared to PNEU-C-7 (87.3% vs. 92.4% in the US study after three doses of vaccine administered at 2, 4, 6 months) and (77.5% vs. 87.1% in the German study after three doses of vaccine at 2, 3, 4 months). Non-inferiority criteria for all secondary outcomes for response to serotype 6B were met, including non-inferiority as assessed by opsonophagocytic assay (OPA).…”

Section: Efficacymentioning

confidence: 99%

“…There was a small but statistically significantly increase in mild induration and erythema in the Tween 80 arm of the study with the first and second doses, but no differences in moderate or severe local adverse events, and statistically fewer infants that reported systemic adverse events after dose two (p<0.05). (41) A total of 2116 (30,33,40,42,43) children received PNEU-C-13 as compared to PNEU-C-7 as a primary series. In one study, there were significant differences between groups in the incidence of induration (28.2% PNEU-C-13 vs. 20.5% PNEU-C-7, P= 0.04) and erythema (27.2% PNEU-C-13 vs. 36.4% PNEU-C-7, P=0.04) after any dose.…”

Section: Vaccine Safety and Adverse Eventsmentioning

confidence: 99%