Skip to main content
Premium Trial:

Request an Annual Quote

Sequencing Study Highlights Vaccine-Dodging Streptococcus Pneumoniae Lineage

Streptococcus Pneumoniae

NEW YORK – New research by members of the Global Pneumococcal Sequencing (GPS) Consortium suggests large-scale genome sequencing can identify key features of a Streptococcus pneumoniae serotype called 24F, which has become prevalent in France and several other countries in the years following the introduction of a 13-serotype-targeting pneumococcal conjugate vaccine (PCV13).

"[C]lassifying strains and testing for drug resistance are time consuming and resource intensive," the study's first and corresponding author Stephanie Lo, a researcher with the Wellcome Sanger Institute's Parasites and Microbes Programme, said in a statement. "Whole-genome sequencing can now reliably infer serotype and antibiotic resistance profiles, identify where outbreaks might be occurring and track which strains mediate serotype replacement. So it's one test that can answer a lot of different questions."

For a paper published in Lancet Microbe on Tuesday, researchers from the Wellcome Sanger Institute, France's National Reference Center for Pneumococci, the Hospital Sant Joan de Deu in Spain, and other centers performed whole-genome sequencing on more than 400 S. pneumoniae isolates from the 24F serotype, collected from children under 18 in France over a decade and a half, from 2003 to 2018.

Together with nearly 25,600 24F S. pneumoniae genomes from the GPS database, the team explained, the sequences made it possible to flag three main lineages within the serotype 24F, classified with Global Pneumococcal Sequence Cluster (GPSC) and clonal complex patterns.

The researchers focused most of their analyses on GPSC10, which appeared to be the main lineage behind the boost in serotype 24 representation in France in the post-vaccination years. Based on nearly 900 GPSC10 isolates characterized internationally, they suggested that the lineage tends to be marked by a range of multi-drug resistance features and is capable of taking on 16 serotypes beyond 24F.

"Due to its recombinogenic nature, this lineage is capable of simultaneously expressing a wide range of serotypes to facilitate its adaptation under the vaccine-selective pressure," the authors reported. "Together with its transmissibility, GPSC10 should therefore be regarded as a high-risk lineage that could diminish the benefits of the vaccination program worldwide over time."

Only half a dozen of the serotypes present in the GPSC10 lineage are targeted by PCV13, the team noted, hinting at the potential hurdles associated with serotype-based vaccine design and development.

Given the "shape-shifter" nature of the S. pneumoniae GPSC10, the National Reference Center for Pneumococci's Emmanuelle Varon, co-senior author on the study, suggested in a statement that "[s]urveillance on pneumococcal disease, such as that implemented in France since 2001, is our best tool to evaluate the impact of vaccine policies and will allow us to detect the emergence of other non-vaccine serotypes."

The study, which received funding from the Bill and Melinda Gates Foundation, Wellcome Sanger Institute, and US Centers for Disease Control and Prevention, also made it possible to retrace the spread of serotype 24F representatives in the GPSC10 lineage within and beyond Europe.

Based on 174 GPSC10-24F isolates found in the genome set from France, the investigators estimated that the bug spread across the country within roughly three to five years, while sequences from Spain suggested that the serotype 24F replaced a serotype targeted by the PCV13 not long after the vaccine was administered to at-risk children.

Given such findings, the authors suggested that GPSC10 "is a challenge for a serotype-based vaccine strategy," and noted that "[m]ore systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal disease."