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.

Fig. 1

(a,b) Percentages of cultured CD4⁺ CD25⁺ T cells reacting with the different antigens as detected by flow cytometry. Box plots graphs: the boundary of the box closest to zero indicates the 25th percentile, a line within the box marks the median, and the boundary of the box furthest from zero indicates the 75th percentile. Whiskers above and below the box indicate the 95th and 5th percentiles. The outlining dots represent the values out of the 95th and 5th percentiles. Horizontal bar is defined at 2% of CD25⁺ CD4⁺ T cells in all the graphs. Statistical results: *P < 0·05 and **P < 0·01.

Fig. 2

Concentration of cytokines [interleukin (IL)-10 and interferon (IFN)-γ] from the supernatants using Rx1 and FL-Rx1 antigens: acute blood from cases (closed circle), convalescent blood from cases (open triangle), blood from controls (closed square).The dots at the bottom of each graph are below the detection limit. Statistical results: *P < 0·05 and **P < 0·01.

Fig. 3

Antibody concentrations against the recombinant pneumococcal surface protein A (PspA) and PsaA antigens in acute and convalescent sera from the patients with pneumococcal disease. Box plot graphs: the boundary of the box closest to zero indicates the 25th percentile, a line within the box marks the median, and the boundary of the box furthest from zero indicates the 75th percentile. Whiskers above and below the box indicate the 95th and 5th percentiles. The outlining dots represent the values out of the 95th and 5th percentiles. Statistical results: *P < 0·05 and **P < 0·01.