Natural Development of Antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Protein Antigens during the First 13 Years of Life

Abstract

j Conserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. We evaluated the natural development of antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins during childhood. Serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). We also analyzed serum samples from 24 adults. Serum IgG antibodies against eight pneumococcal proteins (Ply, CbpA, PspA 1 and 2, PcpA, PhtD, StkP-C, and PcsB-N), three H. influenzae proteins, and five M. catarrhalis proteins were measured using a multiplexed bead-based immunoassay. Antibody levels were analyzed using multilevel mixed-effects regression and Spearman's correlation. Antibody levels against pneumococcal proteins peaked at 3 to 5 years of age and then reached a plateau. Antibody levels against H. influenzae proteins peaked during the second year and then stabilized. Antibody levels against M. catarrhalis proteins peaked during the first year and then slowly decreased. Peak antibody levels during childhood were higher than those of adults. Correlations among pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD antibodies (r ‫؍‬ 0.71 to 0.75; P < 0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve prediction of antibody levels in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.

Immune exclusion by naturally acquired secretory IgA against pneumococcal pilus-1

“…based on serum IgG levels (64). Likewise, anti-pilus antibodies are commonly found in humans, and reach maximum levels around 10-15 years of age (31).…”

Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae

“…Having established that hexamer-enhancing variants of CPS6-IgG1 strongly induce phagocytosis of serogroup 6 and serotype 19A strains, we studied whether these antibodies also trigger intracellular killing of bacteria by neutrophils. To mimic the natural situation more closely, we now performed experiments in normal human serum (NHS) that contains pre-existing antibodies (62,63) instead of using IgG/IgM-depleted serum as a complement source. This is important because 6B and 19A serotypes circulate in the healthy population and naturally occurring antibodies could thus play an additional role in phagocytosis by the mAbs.…”

Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children

“…We therefore undertook a post-hoc analysis of acute IgG to pneumococcal proteins in children ≥2 years of age for the etiological diagnosis of pneumonia. Children ≥2 years of age known to have a qualitatively different humoral immune response to pneumococcal polysaccharide antigens, although not pneumococcal protein antigens, in comparison with young infants (Clutterbuck et al, 2007;Borges et al, 2016;Ramos-Sevillano et al, 2019). The clinical characteristics of children ≥2 .…”

“…We used five pneumococcal proteins as target antigens (choline binding protein A, CbpA; protein for cell wall separation of group B streptococci, PcsB; pneumococcal histidine triad D, PhtD; pneumolysin, Ply; serine threonine kinase protein C, StkpC). These antigens are thought to be expressed by all pathogenic pneumococci, are specific to pneumococci or closely related species, and have been used to assess the serological response to pneumococcal pneumonia (Andrade et al, 2014Borges et al, 2016).…”