Dynamic changes in paediatric invasive pneumococcal disease after sequential switches of conjugate vaccine in Belgium: a national retrospective observational study

Efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) was inferred before licensure from an aggregate correlate of protection established for the seven-valent vaccine (PCV7). We did a postlicensure assessment of serotype-specific vaccine effectiveness and immunogenicity in England, Wales, and Northern Ireland to derive the correlates of protection for individual serotypes. We assessed vaccine effectiveness against invasive pneumococcal disease using the indirect cohort method. We measured serotype-specific IgG concentration in infants after they were given two priming doses of PCV7 (n=126) or PCV13 (n=237) and opsonophagocytic antibody titre from a subset of these infants (n=100). We derived correlates of protection by relating percentage protection to a threshold antibody concentration achieved by an equivalent percentage of infants. We used multivariable logistic regression to estimate vaccine effectiveness and reverse cumulative distribution curves to estimate correlates of protection. For the 706 cases of invasive pneumococcal disease included in the study, PCV13 vaccine effectiveness after two doses before age 12 months or one dose from 12 months was 75% (95% CI 58-84). Vaccine effectiveness was 90% (34-98) for the PCV7 serotypes and 73% (55-84) for the six additional serotypes included in PCV13. Protection was shown for four of the six additional PCV13 serotypes (vaccine effectiveness for serotype 3 was not significant and no cases of serotype 5 infection occurred during the observation period). The vaccine effectiveness for PCV13 and PCV7 was lower than predicted by the aggregate correlate of protection of 0·35 μg/mL used during licensing. Calculated serotype-specific correlates of protection were higher than 0·35 μg/mL for serotypes 1, 3, 7F, 19A, 19F, and lower than 0·35 μg/mL for serotypes 6A, 6B, 18C, and 23F. Opsonophagocytic antibody titres of 1 in 8 or higher did not predict protection. PCV13 provides significant protection for most of the vaccine serotypes. Although use of the aggregate correlate of protection of 0·35 μg/mL has enabled the licensing of effective new PCVs, serotype-specific correlates of protection vary widely. The relation between IgG concentration after priming and long-term protection needs to be better understood. Public Health England and UK Department of Health Research and Development Directorate. Copyright © 2014 Elsevier Ltd. All rights reserved.

In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children. Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype). In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules. In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes. Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.