Estimating the Vaccine Effectiveness Against Serotype 3 for the 13-Valent Pneumococcal Conjugate Vaccine: A Dynamic Modeling Approach

Abstract

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) is the only PCV licensed to protect against serotype 3 in children. However, conflicting estimates exist of PCV13's direct and indirect protection vaccine effectiveness (VE) for serotype 3. Objective: Our study examined the of PCV13 for serotype 3 using different assumptions for PCV13 direct and indirect VE to model trends in serotype 3 invasive pneumococcal disease (IPD) and comparing these to observed data from the United Kingdom (UK). Methods: A dynamic transmission model of the spread of pneumococcal carriage and development of IPD was used to fit pre-PCV13-modeled IPD incidence with observed data. To allow for comparison across scenarios, post-PCV13-modeled IPD incidence was fit to observed data using assumptions for three different scenarios: (scenario 1) serotype 3 as a nonvaccine serotype, (scenario 2) VE against serotype 3 IPD of 63.5% based on a recent meta-analysis, and (scenario 3) a model-estimated VE against serotype 3. Results: Post-PCV13 introduction, modeled 2017 and average annual serotype 3 IPD incidence were within 20% and 59% of observed values for scenarios 2 and 3, respectively, but deviated by >100% for scenario 1. For adults aged ≥65 years, modeled 2017 IPD incidence in scenario 1 differed from observed data by 16% versus roughly 8% in scenarios 2 and 3. Conclusions: Observed data do not support a scenario of no serotype 3 VE, but rather a combination of direct protection among vaccinated children and a lower level of indirect protection among older adults. Policymakers should consider transmission dynamics when examining VE against covered serotypes.

Streptococcus pneumoniaeserotype 3 population structure in the era of conjugate vaccines, 2001-2018

“…The temporality of clade II's increase and corresponding global increase in serotype 3 IPD in relation to the introduction of PCV13 posits a putative association. Surveillance data from countries that introduced PCV13 and PCV10 (which lacks the serotype 3 component) suggests at least some direct and indirect protection against serotype 3 from PCV13 [53][54][55]. While we observed serotype 3 IPD among fully vaccinated children and adults in this study, our design did not permit assessment of vaccine effectiveness nor differential incidence rates of clade I and clade II disease among vaccinated and unvaccinated individuals.…”

Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001–2018

“…The temporality of clade II ’s increase and corresponding global increase in serotype 3 IPD in relation to the introduction of PCV13 posits a putative association. Surveillance data from countries that introduced PCV13 and PCV10 (which lacks the serotype 3 component) suggest at least some direct and indirect protection against serotype 3 from PCV13 [ 54 56 ]. While we observed serotype 3 IPD among fully vaccinated children and adults in this study, our design did not permit assessment of vaccine effectiveness nor differential incidence rates of clade I and clade II disease among vaccinated and unvaccinated individuals.…”

Pneumococcal Conjugate Vaccine Impact on Serotype 3: A Review of Surveillance Data

“…We updated a recently published transmission dynamic model to ascertain whether PCV13 provides direct or indirect protection for serotype 3 [ 12 , 13 ]. Briefly, the model used the UK surveillance system and stratified individuals by the presence or absence of pneumococcal carriage, vaccine status, and age group.…”

“…First, we reviewed the publicly available surveillance data from countries identified in two recently published reviews [ 10 , 11 ] to describe the population impact of pediatric PCV13 or PCV10 vaccination programs on serotype 3 IPD (Analysis 1). We then compared the observed trends in PCV10 and PCV13 countries to a previously described dynamic transmission model that simulates the spread of pneumococcal carriage and development of IPD in a population over time (Analysis 2) [ 12 , 13 ].…”