Persistent Circulation of Vaccine Serotypes and Serotype Replacement After 5 Years of Infant Immunization With 13-Valent Pneumococcal Conjugate Vaccine in the United Kingdom

Kandasamy, Rama; Voysey, Merryn; Collins, Sarah; Berbers, Guy A. M.; Robinson, Hannah; Noel, Irene; Hughes, Henry J.; Ndimah, Susan; Gould, Katherine A.; Fry, Norman K.; Sheppard, Carmen; Ladhani, Shamez; Snape, Matthew D.; Hinds, Jason; Pollard, Andrew J.

doi:10.1093/infdis/jiz178

Cited by 47 publications

(52 citation statements)

References 16 publications

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“…In the UK, a national pneumococcal vaccination policy with 7-valent PCV was introduced for children under 2 years old in September 2006 and replaced with the 13-valent PCV in 2010 [ 3 ]. Subsequent reductions in invasive pneumococcal disease (IPD) and nasopharyngeal carriage due to vaccine serotypes in children were observed [ 4 ]. Reductions in vaccine type IPD and non-invasive pneumococcal pneumonia (NIPP) in adults followed, largely due to herd protection effects [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent reductions in invasive pneumococcal disease (IPD) and nasopharyngeal carriage due to vaccine serotypes in children were observed [ 4 ]. Reductions in vaccine type IPD and non-invasive pneumococcal pneumonia (NIPP) in adults followed, largely due to herd protection effects [ 4 ]. However, with the emergence of replacement serotypes in the UK, recent studies have observed increases in the incidence rates of IPD and pneumococcal pneumonia due to non-PCV13 serotypes [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: A case-control test-negative design study

et al. 2020

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Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is available in the United Kingdom to adults aged 65 years or older and those in defined clinical risk groups. We evaluated the vaccine effectiveness (VE) of PPV23 against vaccine-type pneumococcal pneumonia in a cohort of adults hospitalised with community-acquired pneumonia (CAP). Methods and findings Using a case-control test-negative design, a secondary analysis of data was conducted from a prospective cohort study of adults (aged ≥16 years) with CAP hospitalised at 2 university teaching hospitals in Nottingham, England, from September 2013 to August 2018. The exposure of interest was PPV23 vaccination at any time point prior to the index admission. A case was defined as PPV23 serotype-specific pneumococcal pneumonia and a control as non-PPV23 serotype pneumococcal pneumonia or nonpneumococcal pneumonia. Pneumococcal serotypes were identified from urine samples using a multiplex immunoassay or from positive blood cultures. Multivariable logistic regression was used to derive adjusted odds of case status between vaccinated and unvaccinated individuals; VE estimates were calculated as (1 − odds ratio) × 100%. Of 2,357 patients, there were 717 PPV23 cases (48% vaccinated) and 1,640 controls (54.5% vaccinated). The adjusted VE (aVE) estimate against PPV23 serotype disease was 24% (95% CI 5%–40%, p = 0.02). Estimates were similar in analyses restricted to vaccine-eligible patients ( n = 1,768, aVE 23%, 95% CI 1%–40%) and patients aged ≥65 years ( n = 1,407, aVE 20%, 95% CI −5% to 40%), but not in patients aged ≥75 years ( n = 905, aVE 5%, 95% CI −37% to 35%). The aVE estimate in relation to PPV23/non-13-valent pneumococcal conjugate vaccine (PCV13) serotype pneumonia ( n = 417 cases, 43.7% vaccinated) was 29% (95% CI 6%–46%). Key limitations of this study are that, due to high vaccination rates, there was a lack of power to reject the null hypothesis of no vaccine effect, and that the study was not large enough to allow robust subgroup analysis in the older age groups. Conclusions In the setting of an established national childhood PCV13 vaccination programme, PPV23 vaccination of clinical at-risk patient groups and adults aged ≥65 years provided moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. These findings suggest that PPV23 vaccination may continue to have an important role in adult pneumococcal vaccine policy, including the possibility of revaccination of older adults.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: A case-control test-negative design study

et al. 2020

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“…Discovery of serotype 6C allowed one to show that 7-valent PCV (PCV7) was cross-protective against 6A but not 6C (12), and helped improve PCV design. Like 6C, epidemiologic surveys have not distinguished 10D from 10A so far and reported increased prevalence of "10A" following the use of PCVs in children (36)(37)(38)(39). One should now consider that PCV usage may have increased the prevalence of 10D as well as 10A.…”

Section: Discussionmentioning

confidence: 98%

A New Pneumococcal Capsule Type, 10D, is the 100th Serotype and Has a Large cps Fragment from an Oral Streptococcus

Ganaie

Saad

McGee

et al. 2020

mBio

267

194

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Streptococcus pneumoniae (pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D, by determining its unique chemical structure and biosynthetic roles of all capsule synthesis locus (cps) genes. The name 10D reflects its serologic cross-reaction with serotype 10A and appearance of cross-opsonic antibodies in response to immunization with 10A polysaccharide in a 23-valent pneumococcal vaccine. Genetic analysis showed that 10D cps has three large regions syntenic to and highly homologous with cps loci from serotype 6C, serotype 39, and an oral streptococcus strain (S. mitis SK145). The 10D cps region syntenic to SK145 is about 6 kb and has a short gene fragment of wciNα at the 5′ end. The presence of this nonfunctional wciNα fragment provides compelling evidence for a recent interspecies genetic transfer from oral streptococcus to pneumococcus. Since oral streptococci have a large repertoire of cps loci, widespread PCV usage could facilitate the appearance of novel serotypes through interspecies recombination. IMPORTANCE The polysaccharide capsule is essential for the pathogenicity of pneumococcus, which is responsible for millions of deaths worldwide each year. Currently available pneumococcal vaccines are designed to elicit antibodies to the capsule polysaccharides of the pneumococcal isolates commonly causing diseases, and the antibodies provide protection only against the pneumococcus expressing the vaccine-targeted capsules. Since pneumococci can produce different capsule polysaccharides and therefore reduce vaccine effectiveness, it is important to track the appearance of novel pneumococcal capsule types and how these new capsules are created. Herein, we describe a new and the 100th pneumococcal capsule type with unique chemical and serological properties. The capsule type was named 10D for its serologic similarity to 10A. Genetic studies provide strong evidence that pneumococcus created 10D capsule polysaccharide by capturing a large genetic fragment from an oral streptococcus. Such interspecies genetic exchanges could greatly increase diversity of pneumococcal capsules and complicate serotype shifts.

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“…5,6 In European countries where nasopharyngeal carriage studies have been performed, the main predominant serotypes are now 15B/C, 11A, 23B, 15A, 35B, 10A, 21, and 23A. [5][6][7] This distribution seems relatively similar among countries. [5][6][7]…”

Section: Diversity Of Nasopharyngeal Emerging Serotypesmentioning

confidence: 97%

“…A study from the United Kingdom reported an increase in incidence of serotypes 12F, 24F, and 23B in 2015. 7 In Israel, Rokney et al described a steady increase in incidence of IPDs due to serotype 12F, in all age groups, including children <2 years old. 3 In addition, the frequency of serotype 2 in IPD increased, but with an epidemic evolution.…”

Section: Diversity Of Emerging Serotypes In Ipdsmentioning

confidence: 99%

Diversity of Serotype Replacement After Pneumococcal Conjugate Vaccine Implementation in Europe

Lévy

Ouldali

Caeymaex

et al. 2019

The Journal of Pediatrics

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treptococcus pneumoniae is the leading cause of bacterial infections in children, including meningitis, bacteremia, bacteremic pneumonia, empyema, and mucosal infections such as otitis media and nonbacteremic pneumonia. After the implementation of pneumococcal conjugate vaccines (PCVs), worldwide, the burden of invasive pneumococcal diseases (IPDs) and non-invasive pneumococcal diseases due to vaccine serotypes (VTs) greatly decreased in children. 1 However, since 2015, several European countries have reported an increased incidence of IPDs due to non-vaccine serotypes (NVTs), which seemed variable across countries in terms of magnitude, serotypes involved, and clinical entities. 1-4 This led to questions regarding the long-term benefit of PCVs. This commentary presents an overview of serotype replacement in pneumococcal carriage and diseases in Europe, with a focus on IPDs. The aim is to raise awareness among pediatricians and healthcare professionals of the potential factors involved in the phenomenon of serotype replacement diversity after PCV implementation. In addition, we analyze the potential factors involved in this phenomenon. We selected European observational studies assessing the impact of PCV10 and PCV13 beyond 5 years after their implementation at the population level in children. We reviewed the literature in MEDLINE via PubMed, with no time or language restriction (last search June 30, 2019). The search algorithm was based on a combination of terms related to "13-or 10-valent PCV," "pneumococcal diseases or pneumococcal carriage," and "impact/effect/change." We completed this search by screening the reference lists of the selected articles.

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Persistent Circulation of Vaccine Serotypes and Serotype Replacement After 5 Years of Infant Immunization With 13-Valent Pneumococcal Conjugate Vaccine in the United Kingdom

Cited by 47 publications

References 16 publications

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: A case-control test-negative design study

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: A case-control test-negative design study

A New Pneumococcal Capsule Type, 10D, is the 100th Serotype and Has a Large cps Fragment from an Oral Streptococcus

Diversity of Serotype Replacement After Pneumococcal Conjugate Vaccine Implementation in Europe

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