Exploring the role of competition induced by non-vaccine serotypes for herd protection following pneumococcal vaccination

Abstract

The competitive pressure from non-vaccine serotypes may have helped pneumococcal conjugate vaccines (PCVs) to limit vaccine-type (VT) serotype prevalence. We aimed to investigate if, consequently, the indirect protection of vaccines targeting most pneumococcal serotypes could fall short of the profound effects of current formulations. We compared three previously described pneumococcal models harmonized to simulate 20 serotypes with a combined pre-vaccination prevalence in children younger than 5-years-old of 40%. We simulated vaccines of increasing valency by adding serotypes in order of their competitiveness and explored their ability to reduce VT carriage by 95% within 10 years after introduction. All models predicted that additional valency will reduce indirect vaccine effects and hence the overall vaccine impact on carriage both in children and adults. Consequently, the minimal effective coverage (efficacy against carriage×vaccine coverage) needed to eliminate VT carriage increased with increasing valency. One model predicted this effect to be modest, while the other two predicted that high-valency vaccines may struggle to eliminate VT pneumococci unless vaccine efficacy against carriage can be substantially improved. Similar results were obtained when settings of higher transmission intensity and different PCV formulations were explored. Failure to eliminate carriage as a result of increased valency could lead to overall decreased impact of vaccination if the disease burden caused by the added serotypes is low. Hence, a comparison of vaccine formulations of varying valency, and pan-valent formulations in particular, should consider the invasiveness of targeted serotypes, as well as efficacy against carriage.

Keywords: herd protection; pneumococcus; serotype competition; vaccination.

Figure 1.

Model demographics and serotypes distribution before the introduction of vaccination. (a) The age distribution of the model populations. (b) A stacked barplot to illustrate the predicted serotype distributions (stacked prevalence of serotype-specific carriage episodes scaled to the overall carriage prevalence) in children and the rest of the population in low and high transmission settings. The grey line indicates the targeted prevalence. (Online version in colour.)

Figure 2.

Predicted percentage reduction in the prevalence of pneumococcal carriage (bottom row), VT carriage (middle row) and carriage of the most competitive serotype (top row) 10 years after vaccine introduction, assuming 55% efficacy against acquisition of pneumococcal VTs and 100% coverage. (Online version in colour.)

Figure 3.

Percentage reduction in the prevalence of pneumococcal carriage 10 years after introduction of a PCV-like vaccine, assuming 55% efficacy against acquisition of pneumococcal VTs and 100% coverage. (Online version in colour.)

Figure 4.

The effective coverage needed to prevent 95% of VT carriage 10 years after the start of vaccination, assuming serotypes are added to the vaccine in order of their carriage prevalence. At valency 7 and 10, the respective effective coverage for PCV7/10-like and PCV13/15-like vaccines are indicated by large dots and triangles in respective colours. (Online version in colour.)