Abstract

Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths globally. The objective of this study was to determine the distribution and clonal type variability of three potential vaccine antigens: Pneumococcal serine-rich repeat protein (PsrP), Pilus-1, and Pneumococcal choline binding protein A (PcpA) among pneumococcal isolates from children with invasive pneumococcal disease and healthy nasopharyngeal carriers. We studied by Real-Time PCR a total of 458 invasive pneumococcal isolates and 89 nasopharyngeal pneumococcal isolates among children (total = 547 strains) collected in Barcelona, Spain, from January 2004 to July 2010. pcpA, psrP and pilus-1 were detected in 92.8%, 51.7% and 14.4% of invasive isolates and in 92.1%, 48.3% and 18% of carrier isolates, respectively. Within individual serotypes the prevalence of psrP and pilus-1 was highly dependent on the clonal type. pcpA was highly prevalent in all strains with the exception of those belonging to serotype 3 (33.3% in serotype 3 isolates vs. 95.1% in other serotypes; P<.001). psrP was significantly more frequent in those serotypes that are less apt to be detected in carriage than in disease; 58.7% vs. 39.1% P<.001. Antibiotic resistance was associated with the presence of pilus-1 and showed a negative correlation with psrP. These results indicate that PcpA, and subsequently Psrp and Pilus-1 together might be good candidates to be used in a next-generation of multivalent pneumococcal protein vaccine.

Highlights

  • Invasive disease caused by Streptococcus pneumoniae is responsible for more than 1.6 million childhood deaths worldwide every year [1]

  • We examined a total of 458 invasive pneumococcal isolates and 89 nasopharyngeal pneumococcal isolates among children

  • Among invasive pneumococcal disease (IPD) isolates, the prevalence of serotypes included in the commercialized conjugate vaccines PCV7, PCV10 and PCV13 were 14.2% (65 isolates), 58.3% (267 isolates) and 83.6% (383 isolates) respectively

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Summary

Introduction

Invasive disease caused by Streptococcus pneumoniae is responsible for more than 1.6 million childhood deaths worldwide every year [1]. In certain developed countries, including Spain, despite vaccination with a 7-valent conjugate vaccine against capsular polysaccharide (PCV-7), pneumococcal pneumonia remains a major cause of pediatric hospital admission [2,3,4]. PCV-7 is composed of capsular polysaccharide from serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 and has proved to be effective in preventing pneumococcal disease caused by these serotypes in children [5]. PCV7 prevents invasive pneumococcal disease (IPD) in adult and nonvaccinated children by an indirect effect (herd immunity) on pneumococcal transmission [5,6]. Pneumococcal disease remains a major medical problem with an urgent need for an improved vaccine

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