Variants of Streptococcus pneumoniae Serotype 14 from Papua New Guinea with the Potential to Be Mistyped and Escape Vaccine-Induced Protection

Sam Manna, Leena Spry, Ashleigh Wee-Hee, Belinda D Ortika, Laura K Boelsen, Steven Batinovic, Nadia Mazarakis, Rebecca L Ford, Stephanie W Lo, Stephen D Bentley, Fiona M Russell, Christopher C Blyth, William S Pomat, Steve Petrovski, Jason Hinds, Paul V Licciardi, Catherine Satzke

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4 Citations (SciVal)


Streptococcus pneumoniae (the pneumococcus) is a human pathogen of global importance, classified into serotypes based on the type of capsular polysaccharide produced. Serotyping of pneumococci is essential for disease surveillance and vaccine impact measurement. However, the accuracy of serotyping methods can be affected by previously undiscovered variants. Previous studies have identified variants of serotype 14, a highly invasive serotype included in all licensed vaccine formulations. However, the potential of these variants to influence serotyping accuracy and evade vaccine-induced protection has not been investigated. In this study, we screened 1,386 nasopharyngeal swabs from children hospitalized with acute respiratory infection in Papua New Guinea for pneumococci. Swabs containing pneumococci (n = 1,226) were serotyped by microarray to identify pneumococci with a divergent serotype 14 capsule locus. Three serotype 14 variants ('14-like') were isolated and characterized further. The serotyping results of these isolates using molecular methods varied depending on the method, with 3/3 typing as nontypeable (PneumoCaT), 3/3 typing as serotype 14 (seroBA), and 2/3 typing as serotype 14 (SeroCall and quantitative PCR). All three isolates were nontypeable by phenotypic methods (Quellung and latex agglutination), indicating the absence of capsule. Illumina and nanopore sequencing were employed to examine their capsule loci and revealed unique mutations. Lastly, when incubated with sera from vaccinated individuals, the 14-like isolates evaded serotype-specific opsonophagocytic killing. Our study highlights the need for phenotypic testing to validate serotyping data derived from molecular methods. The convergent evolution of capsule loss underscores the importance of studying pneumococcal population biology to monitor the emergence of pneumococci capable of vaccine escape, globally. IMPORTANCE Pneumococcus is a pathogen of major public health importance. Current vaccines have limited valency, targeting a subset (up to 20) of the more than 100 capsule types (serotypes). Precise serotyping methods are therefore essential to avoid mistyping, which can reduce the accuracy of data used to inform decisions around vaccine introduction and/or maintenance of national vaccination programs. In this study, we examine a variant of serotype 14 (14-like), a virulent serotype present in all currently licensed vaccine formulations. Although these 14-like pneumococci no longer produce a serotype 14 capsule, widely used molecular methods can mistype them as serotype 14. Importantly, we show that 14-like pneumococci can evade opsonophagocytic killing mediated by vaccination. Despite the high accuracy of molecular methods for serotyping, our study reemphasizes their limitations. This is particularly relevant in situations where nonvaccine type pneumococci (e.g., the 14-likes in this study) could potentially be misidentified as a vaccine type (e.g., serotype 14).

Original languageEnglish
Pages (from-to)e0152422
JournalMicrobiology Spectrum
Issue number4
Early online date12 Jul 2022
Publication statusPublished - 31 Aug 2022

Bibliographical note

This study was supported by a Robert Austrian Research Award in Pneumococcal Vaccinology awarded to S.M. by ISPPD (funded by Pfizer) as well as by the National Health and Medical Research Council (NHMRC) Centre of Research Excellence for Pneumococcal Disease Control in the Asia-Pacific (GNT1196415). This work was also supported by the Victorian Government’s Operational Infrastructure Support Program. P.V.L. is a recipient of an NHMRC Career Development Fellowship (GNT1146198). During the study period, C.C.B. was a recipient of a NHMRC Career Development Fellowship (GNT1111596) and an Investigator Award (GNT1173163). F.M.R. holds a NHMRC Investigator Award (GNT1177245). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.


  • Child
  • Humans
  • Papua New Guinea/epidemiology
  • Pneumococcal Infections/prevention & control
  • Pneumococcal Vaccines
  • Serogroup
  • Serotyping/methods
  • Streptococcus pneumoniae/genetics


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