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Differences in Homing Potentials of Streptococcus pneumoniae-Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations.

ABSTRACT: Mucosal immune mechanisms in the upper and lower respiratory tracts may serve a critical role in preventing pneumonia due to Streptococcus pneumoniae. Streptococcus pneumoniae-specific plasmablasts presumably originating in the lower respiratory tract have recently been found in the circulation in patients with pneumonia. The localization of an immune response can be evaluated by exploring homing receptors on such plasmablasts, yet no data have thus far described homing receptors in pneumonia.The expression of ?4?7, L-selectin, and cutaneous lymphocyte antigen (CLA) on S. pneumoniae-specific plasmablasts was examined in patients with pneumonia (n = 16) and healthy volunteers given pneumococcal polysaccharide vaccine (PPV; n = 14) or pneumococcal conjugate vaccine (PCV; n = 11).In patients with pneumonia, the proportion of S. pneumoniae-specific plasmablasts expressing L-selectin was high, the proportion expressing ?4?7 was moderate, and the proportion expressing CLA was low. The homing receptor ?4?7 was expressed more frequently in the pneumonia group than in the PPV (P = .000) and PCV (P = .029) groups, L-selectin was expressed more frequently in the PPV group than in the PCV group (P = .014); and CLA was expressed more frequently in the pneumonia group than in the PPV group (P = .001).The homing receptor profile in patients with pneumonia was unique yet it was closer to that in PCV recipients than in PPV recipients. These data suggest greater mucosal localization for immune response in natural infection, which is clinically interesting, especially considering the shortcomings of vaccines in protecting against noninvasive pneumonia.

SUBMITTER: Palkola NV

PROVIDER: S-EPMC4577046 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Differences in Homing Potentials of Streptococcus pneumoniae-Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations.

Palkola Nina V NV Pakkanen Sari H SH Kantele Jussi M JM Pakarinen Laura L Puohiniemi Ritvaleena R Kantele Anu A

The Journal of infectious diseases 20150402 8

<h4>Background</h4>Mucosal immune mechanisms in the upper and lower respiratory tracts may serve a critical role in preventing pneumonia due to Streptococcus pneumoniae. Streptococcus pneumoniae-specific plasmablasts presumably originating in the lower respiratory tract have recently been found in the circulation in patients with pneumonia. The localization of an immune response can be evaluated by exploring homing receptors on such plasmablasts, yet no data have thus far described homing recept ...[more]

PMID: 25838267

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Project description:UnlabelledThe use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two different Streptococcus pneumoniae serotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotype in vitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.ImportanceCurrent thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology of Streptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.

Project description:IntroductionStreptococcus pneumoniae is a leading cause of pneumonia among children. However, owing to diagnostic limitations, the protection conferred by pneumococcal conjugate vaccines (PCVs) against pediatric pneumonia attributable to vaccine-serotype pneumococci remains unknown.MethodsWe analyzed data on vaccination and nasopharyngeal pneumococcal detection among children <5 years old with community-acquired alveolar pneumonia (CAAP; "cases") and those without respiratory symptoms ("controls"), who were enrolled in population-based prospective surveillance studies in southern Israel between 2009 and 2018. We measured PCV-conferred protection against carriage of vaccine-serotype pneumococci via the relative risk of detecting these serotypes among vaccinated versus unvaccinated controls. We measured protection against progression of vaccine serotypes from carriage to CAAP via the relative association of vaccine-serotype detection in the nasopharynx with CAAP case status, among vaccinated and unvaccinated children. We measured PCV-conferred protection against CAAP attributable to vaccine-serotype pneumococci via the joint reduction in risks of carriage and disease progression.ResultsOur analyses included 1032 CAAP cases and 7743 controls. At ages 12-35 months, a PCV13 schedule containing 2 primary doses and 1 booster dose provided 87.2% (95% confidence interval: 8.1-100.0%) protection against CAAP attributable to PCV13-serotype pneumococci, and 92.3% (-0.9%, 100.0%) protection against CAAP attributable to PCV7-serotype pneumococci. Protection against PCV13-serotype and PCV7-serotype CAAP was 67.0% (-424.3%, 100.0%) and 67.7% (-1962.9%, 100.0%), respectively, at ages 36-59 months. At ages 4-11 months, 2 PCV13 doses provided 98.9% (-309.8%, 100.0%) and 91.4% (-191.4%, 100.0%) against PCV13-serotype and PCV7-serotype CAAP.ConclusionsAmong children, PCV-conferred protection against CAAP attributable to vaccine-targeted pneumococcal serotypes resembles protection against vaccine-serotype invasive pneumococcal disease.

Dataset Information

Differences in Homing Potentials of Streptococcus pneumoniae-Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations.

Publications

Differences in Homing Potentials of Streptococcus pneumoniae-Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations.

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