Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency

Abstract

Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal polysaccharide conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.

Pneumonia and Invasive Pneumococcal Diseases: The Role of Pneumococcal Conjugate Vaccine in the Era of Multi-Drug Resistance

“…All these considerations underline that the choice between available vaccines is not easy, considering also that the vaccine coverage depends on vaccination countries’ plans and on humoral responses provided by each kind of vaccine; finally, it also depends on the divergent serotype replacement phenomenon and the increasing diversity in pneumococcal diseases in North America, Europe, and Australia. In particular, this aspect leads to the emergence of serotypes with different pathogenicity in each country and in each age group, reducing the benefit of expanding the vaccine valence [ 136 ]. Waiting to see the results of the ongoing research on vaccines not dependent serotypes, it is highly likely that there will be PCV15 and PCV20 on the market, mostly in developing countries, aiming at reducing incidence of pneumococcal infections and the circulation of resistant pathogens.…”

Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life

“…Protein-based vaccines may overcome serotype replacement issues that have emerged following the introduction of pneumococcal conjugate vaccines (PCVs) ( 5 ). Adding additional serotypes into these vaccines can overcome serotype replacement in the short term but, with over 100 pneumococcal serotypes, formulation of a serotype-based pneumococcal vaccine is not possible due to cost and antigen volume required ( 6 , 7 ).…”

A Narrative Review of the Molecular Epidemiology and Laboratory Surveillance of Vaccine Preventable Bacterial Meningitis Agents: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Streptococcus agalactiae

“…However, in the post PCV era, predominance by a single or a few serotypes as causes of IPD was not observed. Instead, increase serotype diversity of invasive pneumococci recovered from IPD cases has been observed [ 66 ], which may challenge the usefulness of increasing the valency of PCVs. Two editorials in 2007, “Invasive pneumococcal disease, the target is moving” [ 67 ] and “Serotype replacement in invasive pneumococcal disease: where do we go from here?” [ 68 ] appear to be just as relevant today after two decades of PCV use.…”