Clin Vaccine Immunol. 2016 Aug 31. pii: CVI.00341-16. [Epub ahead of print]
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. Fifty healthy children had serum samples collected from their first months up to the age of 13 years (median sampling interval 6 months). We also analyzed sera from 24 adults. Serum IgG against eight pneumococcal proteins (Ply, CbpA, PspA1 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 3-5 years of age and then reached a plateau. Antibody levels against H. influenzae proteins peaked during the second year, then stabilized. Antibody levels against M. catarrhalis proteins peaked during the first year, then slowly decreased. Peak antibody levels during childhood were higher than adult levels. Correlations between pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD (r=0.71-0.75; p<0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve antibody level prediction in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially between CbpA, PcpA, and PhtD. Antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reach peak levels earlier compared to antibodies against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.
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