Serum Antipneumococcal Antibodies and Pneumococcal Colonization in Adults with Chronic Obstructive Pulmonary Disease

Abstract

Antibodies to pneumococcus are thought to represent the primary mechanism of naturally acquired resistance to colonization. Here, however, we show that, in patients with chronic obstructive pulmonary disease (COPD), resistance to pneumococcal colonization is not associated with higher concentrations of serum anti-capsular or -noncapsular antibodies. We compared preacquisition serum antibody concentrations to capsular antigens 6B, 7F, 14, 19F, and 23F from patients with COPD who did and did not acquire pneumococcal respiratory tree colonization over the course of 2 years. Colonized patients did not have lower anti-capsular antibody concentrations than control subjects who did not acquire pneumococcus. We found no difference in functional antibody concentrations between colonized patients and control subjects. Furthermore, colonized patients had significantly higher preacquisition concentration of antibody directed against the whole cell and pneumococcal surface protein A than control subjects. We thus conclude that, in adult patients with COPD, resistance to pneumococcal colonization is unlikely to be determined by higher serum antibody concentrations to pneumococcal antigens.Streptococcus pneumoniae is an important human pathogen causing asymptomatic carriage as well as important mucosal and systemic infections. Anti-capsular antibodies are thought to represent the single most important protective mechanism against invasive disease [1]. Antibodies to pneumococcal capsular polysaccharides were the basis of serum therapy in which passively transferred, serotype-specific antipneumococcal serum was shown to reduce mortality from pneu- mococcal pneumonia by half [2]. The development of pneumococcal polysaccharide vaccines for adults [3] and the efficacy of pneumococcal polysaccharide-protein conjugate vaccines in infants and children [4,5] have confirmed that antibodies to polysaccharide antigens can provide excellent protection against invasive disease caused by pneumococci of the same serotype as well as that caused by cross-reacting serotypes.Whether these anti-capsular antibodies represent the mechanism whereby unimmunized individuals develop resistance to pneumococcal infection is less clear. We recently presented seroepidemiologic data that suggest otherwise: the risk of invasive pneumococcal disease in childhood decreases in parallel for many different serotypes (which suggests a serotype-transcending mechanism) and before naturally acquired anti-capsular antibodies are detectable [6]. Antibodies to other, noncapsular antigens have also been suggested to mediate acquired resistance to pneumococcal infection [7,8].It has also generally been assumed that resistance

Protection against Nasopharyngeal Colonization byStreptococcus pneumoniaeIs Mediated by Antigen-Specific CD4+T Cells

“…Similar patterns have been suggested for nasopharyngeal carriage (8). Experimental (20,21) and observational (7,16) studies in adults have found little or no evidence that higher anticapsular antibody concentrations are associated with greater protection from colonization.…”

“…Interestingly, there was also significant up-regulation of IL-17 expression (27). In a study of elderly adults with chronic obstructive pulmonary disease, we have shown that systemic antipneumococcal antibodies did not predict resistance to the acquisition of a new pneumococcal strain, suggesting that other mechanisms, possibly including T cells, may be responsible (16). In a recent study, significantly lower proliferative and cytokine peripheral blood T-cell responses to pneumolysin were observed in children who were colonized with S. pneumoniae than in noncolonized children, raising the intriguing hypothesis that T-cell responses to this antigen may be associated with increased resistance to pneumococcal colonization (35).…”

Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease

“…A recent study also reported that higher levels of antipneumococcal antibodies did not correlate with protection from pneumococcal colonization in patients with COPD [35]. Therefore, the question arises as to why an additional increase of IgG in sera is required for preventing infectious acute exacerbation in COPD patients.…”

Superior Immune Response to Protein-Conjugate versus Free Pneumococcal Polysaccharide Vaccine in Chronic Obstructive Pulmonary Disease

“…First, although the greater immunogenicity of PCV7 may provide improved protection against invasive pneumococcal disease and pneumonia, it is not clear that the vaccine will prevent acute exacerbations of COPD. Prior studies have shown that patients with COPD are frequently colonized with S pneumoniae and that this colonization is a predictor of subsequent exacerbation, but higher levels of anti-pneumococcal IgG and OPK have not been associated with bacterial clearance (25). It is possible that protein-conjugate vaccines may elicit greater IgA antibody responses as compared with polysaccharide vaccines and this may augment the mucosal immune response and better protect against both colonization and exacerbation (26).…”