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Response to pneumococcal infection or vaccination in immunocompetent and immunocompromised children

Defense Thèse de privat-docent : Univ. Genève, 2011
Abstract Streptococcus pneumoniae is one of the most important pathogen in childhood. We explored different aspects of immune responses to S. pneumoniae to better understand how natural protection against the disease is performed. The ultimate goal is to find diagnostic procedures to recognize pneumococcal disease in children, but also to identify strategies to protect children against S. pneumoniae, especially those at risk for severe disease. Hypothesis I Pneumococcal surface proteins- which act in vivo as virulence factors of S. pneumoniae- elicit immunogenic responses in children and can therefore be used for diagnostic purposes. This seroresponse may protect children against future disease. Methods I Seroresponses to different pneumococcal surface proteins were examined in different settings: A) In healthy young children B) In young children with pneumococcal bacteremia C) In children with community-acquired pneumonia Results I A) In healthy young children, we showed that antibodies against PcpA were measured at a younger age than against PhtD or PrtA, showing a distinct pattern for each pneumococcal surface protein. In addition, nasopharyngeal carriage played a significant role in producing higher antibody concentrations. B) In bacteremic young children, seroresponses was elicited in only approximately 50% of children. Younger children even showed an antibody-depleting effect after their disease. Serology-based diagnosis in young children is therefore unreliable. C) Low anti-PcpA antibody responses in the acute phase suggested a primary episode of pneumococcal disease. Its protective function is however not known. A combination of several pneumococcal surface proteins' seroresponses increased the likelihood of diagnosing community-acquired pneumococcal pneumonia. Hypothesis II Immunocompromised children can produce serotype-specific pneumococcal antibodies following vaccination. Methods II Iatrogenically immunocompromised children- pediatric orthotopic liver transplant recipients-were immunized against S. pneumoniae and their serotype-specific antibody levels measured. Results II Most liver transplanted children were able to produce protective antibody levels against S. pneumoniae, even while immunocompromised. Hypothesis III Children with recurrent lower respiratory tract infections due mostly to S. pneumoniae have a delayed or impaired maturation of their memory B cell compartment. Methods III We compared the B cell compartment and its function in children with recurrent lower respiratory tract infection and in healthy age-matched pediatric controls. Results III The memory B cell compartment, including subtypes, such as switched and IgM memory B cells were already constituted at two years of age in both groups, and could not explain the increased risk for pneumococcal infection.  
Keywords Streptococcus pneumoniaePneumoniaBacteremiaCarriageImmune responsePneumococcal surface proteinsDiagnosisSeroresponsePcpAImmunocompromisedChildrenMemory cellsB cellsIgMLower respiratory tract infectionsRecurrent infections
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POSFAY BARBE, Klara. Response to pneumococcal infection or vaccination in immunocompetent and immunocompromised children. Université de Genève. Thèse de privat-docent, 2011. doi: 10.13097/archive-ouverte/unige:17369 https://archive-ouverte.unige.ch/unige:17369

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Deposited on : 2011-11-09

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