title: Pneumococcal surface protein A (PspA) is effective at eliciting T cell-mediated responses during invasive pneumococcal disease in adults.
abstract: Humoral immune response is essential for protection against invasive pneumococcal disease and this property is the basis of the polysaccharide-based anti-pneumococcal vaccines. Pneumococcal surface protein A (PspA), a cell-wall-associated surface protein, is a promising component for the next generation of pneumococcal vaccines. This PspA antigen has been shown to stimulate an antibody-based immunity. In the present study, we evaluated the capacity of PspA to stimulate CD4+ T cells which are needed for the correct development of a B cell based immune response in humans. Cellular immunity to PspA was evaluated by whole-blood culture with different pneumococcal antigens, followed by flow cytometric detection of activated CD4+CD25+ T cells. T cell-mediated immune responses to recombinant PspA proteins were assessed in acute-phase and convalescent blood from adults with invasive pneumococcal disease and in blood from healthy subjects. All cases had detectable antibodies against PspA on admission. We found that invasive pneumococcal disease induced transient T cell depletion but adaptive immune responses strengthened markedly during convalescence. The increased production of both interleukin (IL)-10 and interferon (IFN)-gamma during convalescence suggests that these cytokines may be involved in modulating antibody-based immunity to pneumococcal disease. We demonstrated that PspA is efficient at eliciting T cell immune responses and antibodies to PspA. This study broadens the applicability of recombinant PspA as potent pneumococcal antigen for vaccination against S. pneumoniae.
authors.affiliation: Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France. baril@pasteur.fr
authors.forename: L
authors.initials: L
authors.lastname: Baril
authors.forename: J
authors.initials: J
authors.lastname: Dietemann
authors.forename: M
authors.initials: M
authors.lastname: Essevaz-Roulet
authors.forename: L
authors.initials: L
authors.lastname: Béniguel
authors.forename: P
authors.initials: P
authors.lastname: Coan
authors.forename: D E
authors.initials: DE
authors.lastname: Briles
authors.forename: B
authors.initials: B
authors.lastname: Guy
authors.forename: G
authors.initials: G
authors.lastname: Cozon
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D011008:Pneumococcal Infections / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; C051592:pneumococcal surface protein A; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma