Search

The 13-valent pneumococcal conjugate vaccine compared with the 7-valent pneumococcal conjugate vaccine (PCV7) significantly reduced nasopharyngeal colonization of single serotypes 1, 6A, 6C, 7F, 19A, and 19F, but not serotype 3 or other PCV7 serotypes; serotype 5 had too few events for analysis.Background. The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed to replace the 7-valent pneumococcal conjugate vaccine (PCV7) based on serological noninferiority criteria. To date no randomized PCV13 pediatric trial has included clinical endpoints.Methods. This randomized double-blind trial compared the impact of PCV13 versus PCV7 on nasopharyngeal (NP) colonization and immunogenicity. Healthy infants were randomized (1:1) to receive PCV7 or PCV13 at ages 2, 4, 6, and 12 months; NP swabs were collected at 2, 4, 6, 7, 12, 13, 18, and 24 months, and blood was drawn at 7 and 13 months. Rates of NP acquisition and prevalence, and serotype-specific immunoglobulin G (IgG) concentrations were assessed.Results. The per protocol analysis population included 881 PCV13 and 873 PCV7 recipients. PCV13 significantly reduced NP acquisition of the additional PCV13 serotypes 1, 6A, 7F, and 19A; the cross-reacting serotype 6C; and the common PCV7 serotype 19F. For serotype 3, and the other PCV7 serotypes, there were no significant differences between the vaccine groups. There were too few serotype 5 events to draw inference. The impact on prevalence at predefined time points was similar to that observed with NP acquisition. PCV13 elicited significantly higher IgG responses for PCV13 additional serotypes and serotype 19F, and similar or lower responses for 6/7 PCV7 serotypes.Conclusions. PCV13 resulted in lower acquisition and prevalence of NP colonization than PCV7 did for 4 additional PCV13 serotypes, and serotypes 6C and 19F. It was comparable with PCV7 for all other common serotypes. These findings predict vaccine effectiveness through both direct and indirect protection.Clinical Trials Registration. NCT00508742. [ABSTRACT FROM AUTHOR]

Background The magnitude of an individual’s serotype-specific immunoglobulin G (IgG) response to a pneumococcal conjugate vaccine (PCV) has been associated with the vaccine’s protective efficacy against carriage of pneumococci of that serotype, though the relationship with other serotypes needs to be understood. Methods Using immunogenicity data collected during a trial comparing the 7-valent (PCV7) and 13-valent (PCV13) vaccines, we measured associations between serotype-specific IgG levels, and used multiple regressions to identify demographic predictors of response. Results Vaccine-induced IgG levels were moderately positively correlated with one another, with pairwise correlation coefficients of 0.40–0.70. Principal component analysis of vaccine-serotype responses yielded one principal component indicating general immune responsiveness, and a second principal component mainly describing responses to serotype 14, which was the least correlated with the other responses. Overall, demographic variables explained only 17.0 and 20.4% of the geometric mean PCV7 and PCV13 responses, respectively. In both groups, older age at the first vaccine dose and shorter time from vaccination to antibody measurement were independently associated with stronger geometric mean responses. Discussion Improved understanding of the nature and causes of variation in immune response may aid in optimizing vaccination schedules and identifying robust correlates of protection. [ABSTRACT FROM AUTHOR]

Background In addition to reducing vaccine-type nasopharyngeal carriage rates, pneumococcal conjugate vaccines (PCVs) may decrease carriage density in vaccinated individuals still carrying vaccine serotypes. However, reduction of carriage density has not been systematically studied. This study compared the effect of PCV13 versus PCV7 on carriage density of the serotypes in PCV13 that are not included in PCV7. Methods This randomized, double-blind study was conducted in southern Israel and included Jewish and Bedouin subjects. Per protocol, 881 and 873 infants received PCV13 and PCV7, respectively, at ages 2, 4, 6, and 12 months. Nasopharyngeal cultures at ages 7, 12, 13, 18, and 24 months were plated using the 4-quadrant semiquantitative method and graded 0 (negative) to 4 (growth in all plate quadrants). In this post hoc analysis, the least squares means of cumulative colonization densities per serotype and serotype combination of the total population and each ethnic subpopulation in each vaccine group were calculated, and differences between vaccine groups derived from a linear model. Results PCV13-vaccinated children still carrying the 6 additional PCV13 serotypes unique to PCV13 showed no significant differences in carriage density compared with the PCV7-vaccinated control group. No differences in carriage density were shown between Jewish and Bedouin subpopulations despite higher carriage rates among Bedouin subjects. Conclusions Although PCV13 vaccination reduces vaccine-type carriage compared with PCV7 vaccination by reducing nasopharyngeal acquisition of the additional PCV13 serotypes as previously reported, the current study lacks evidence of a decrease in carriage density of these serotypes when acquired in vaccinated children. Despite the lack of effect on carriage density observed, surveillance data suggest a dramatic decrease in disease rates after PCV implementation. Thus, the current analysis suggests that PCV’s impact on carriage density has minimal or no impact on vaccine success. ( www.ClinicalTrials.gov : NCT00508742) [ABSTRACT FROM AUTHOR]

Background A prior 7- and 13-valent pneumococcal conjugate vaccine (PCV7 and PCV13) study provided sufficient data ( N = 1754; Jewish, n = 1154; Bedouin, n = 595; other, n = 5) to investigate the association between nasopharyngeal (NP) acquisition of common PCV7 serotypes and cross-reacting 6A (PCV7 + 6A) and IgG concentrations. Methods Using a logistic regression model, serotype specific association between postinfant series IgG concentration (age 7 months) and new NP acquisition between ages 7 and 24 months was assessed and adjusted for ethnicity. From a subset of subjects with new NP acquisition ( n = 9–152 across serotypes studied), new acquisition percentiles and associated IgG concentrations were calculated. Results For the serotypes studied , new NP acquisition rates decreased as IgG concentrations increased. Ethnicity did not influence these associations despite differences in carriage rates. From the subset with new acquisitions, 50% of the events occurred at IgG concentrations >0.61–5.58 μg/mL; and 10% of the acquisitions occurred at IgG concentrations >2.48–17.69 μg/mL. Conclusion Remarkably high IgG concentrations are required to reduce NP acquisition. These IgG concentrations differ between serotypes. Ethnicity did not influence the association between high IgG concentrations and prevention of carriage despite differences in carriage rates. Since carriage determines transmission, these results may have important implications for herd protection. Trial registration: ClinicalTrials.gov number, NCT00508742 ; http://clinicaltrials.gov/ct2/show/NCT00508742 [ABSTRACT FROM AUTHOR]

Background Herd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older in the period 2008–2013. Methods This is a post hoc analysis of two prospective studies from the Netherlands. Serotype specific urinary antigen detection and routine microbiological testing were used to categorize episodes as IPD or non-IPD PCAP caused by 7-valent pneumococcal conjugate vaccine (PCV7), PCV10-7 (three additional PCV10 serotypes), PCV13-10 (three additional PCV13 serotypes), and non-PCV13 serotypes. Proportions per vaccine-serotype group were assessed per year from June 1st to May 31st. Time trends were compared to national IPD data. Results Of 270 non-IPD PCAP episodes with known serotype, PCV7 serotypes decreased from 28% in 2008/2009 to 7% in 2012/2013 ( p -value for trend <0.001). No change in PCV10-7 (19% overall) and PCV13-10 (29% overall) serotypes was observed. Non-PCV13 serotypes increased from 30% in 2008/2009 to 37% in 2012/2013 ( p -value for trend 0.048). Trends corresponded with national IPD data. Conclusion PCV7 serotypes declined in non-IPD PCAP among elderly between 2008 and 2013, comparable to IPD data. No reduction in the additional PCV10 serotypes could be demonstrated within the first two years after PCV10 introduction. [ABSTRACT FROM AUTHOR]

Highlights: [•] In some routine immunization programs, PCV13 is administered in a 2+1 schedule. [•] Summarized immune responses from 2+1 and 3+1 studies of PCV13 with postdose 2 data. [•] Immune responses to the PCV7 serotypes postdose 2 were similar for PCV13 and PCV7. [•] All 13 serotypes showed boosting posttoddler dose in the 2+1 studies. [•] These results support transition from PCV7 to PCV13 in countries with 2+1 schedules. [ABSTRACT FROM AUTHOR]

Abstract: Background: The inclusion of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs in many countries has significantly decreased the incidence of disease caused by Streptococcus pneumoniae. However, a substantial portion of disease remained and, in some areas, there has been an increase in disease produced by serotypes not included in PCV7. A 13-valent pneumococcal conjugate vaccine (PCV13) was studied in healthy Brazilian infants in a phase 3, double-blind, randomized study. Methods: Infants were randomized to receive either PCV7 or PCV13 at 2, 4, 6, (doses 1–3), and 12 (toddler dose) months of age, along with routine pediatric vaccinations (diphtheria, tetanus, whole-cell pertussis, and Haemophilus influenzae type b vaccine). Pneumococcal anticapsular polysaccharide-binding immunoglobulin G (IgG) responses and antibody responses to pertussis antigens were measured 1 month after both dose 3 of the infant series and the toddler dose. Safety and tolerability were also assessed. Results: The proportion of subjects achieving a serotype-specific IgG concentration ≥0.35μg/mL measured 1 month after the infant series was comparable in the PCV13 (≥94.2%) and PCV7 (≥93.0%) groups for the 7 serotypes common to both vaccines. The percentage of responders for the 6 additional serotypes ranged from 87.1 to 100% for PCV13. The percentage of responders varied across the pertussis antigens studied, but was not different in PCV13 and PCV7 recipients. Overall, the safety profile of PCV13 was comparable with that of PCV7. Conclusions: PCV13 was comparable to PCV7 in safety and tolerability, elicited comparable immune responses to the common serotypes, and did not interfere with immune responses to concomitantly administered whole-cell pertussis vaccine. The robust immunogenicity exhibited by PCV13 for the additional serotypes suggests that it could provide significant protection against these serotypes. [Copyright &y& Elsevier]