Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children

Abstract

Background Reduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children. Methods From 2009–2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0–59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses. Results Receiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32–67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4–67%) and 62% (95% CI, 33–83%) protection against PCV13-serotype colonization at ages 13–24 months and 25–59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12–5.00) and 3.33-fold (95% CI, 2.28–4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13–24 months. Conclusions Our results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

Indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute respiratory infection despite heterogeneous vaccine coverage: an observational study in Lao People’s Democratic Republic

“…35 A study from Brazil reported a similar VE with three primary doses of PCV13 at 44.0% (14.2%-63.5%) against VT carriage among children 7-11 months of age, 36 while a study from Israel found a VE of 62% (95% CI 33% to 83%) against PCV13 carriage among children 25-59 months of age. 37 Our results were also lower than estimates of VE for PCV13 from modelling in Malawi, at 66.87% (95% CI 50.49% to 82.26%). 38 The differing estimates may relate to the timing of assessment after vaccine is administered to each child (ie, waning direct effects), since a meta-regression of original efficacy results from PCV7 trials reported VEs ranging from 62% (95% CI 52% to 72%) 4 months after vaccination to 42% (95% CI 19% to 54%) 5 years after vaccination.…”

“…Samples were screened for the presence of pneumococci using quantitative real-time PCR (qPCR) targeting the lytA gene. 19 Samples that were lytA qPCR positive (Ct value <35) or equivocal (Ct value [35][36][37][38][39][40] were cultured for molecular serotyping of pneumococcal isolates by microarray. Samples with Ct >40.0 were considered negative for pneumococcus.…”

Properties of Mucoid Serotype 3 Streptococcus pneumoniae From Children in China

“…The reason for the failure of immunoprophylaxis against serotype 3 S. pneumoniae has not been determined yet. Some studies have suggested that the carriage rate of serotype 3 S. pneumoniae might have played an important role: there was no significant decrease, but even an upward trend in the number of carriers ( Azarian et al., 2018 ; Lewnard et al., 2019 ; Madhi et al., 2020 ). Others suggested that the special characteristics of type 3 capsular polysaccharide may also be an important factor ( Choi et al., 2016 ).…”

Uses of pathogen detection data to estimate vaccine direct effects in case-control studies

“…As an alternative, VE can be estimated by comparing the odds of vaccination and pathogen detection among controls against the "null" odds of vaccination within the control group, irrespective of pathogen detection (20). Such an approach may be advantageous when pathogen…”

“…As an alternative, VE S can be estimated by comparing the odds of vaccination and pathogen detection among controls against the “null” odds of vaccination within the control group, irrespective of pathogen detection (20). Such an approach may be advantageous when pathogen detection data are available only from a subset of all control individuals from whom vaccination data are available (e.g., in the case of expensive or invasive diagnostic procedures (21,22)), or when favored by other design considerations.…”