Development of antibodies to PspA families 1 and 2 in children after exposure to Streptococcus pneumoniae

Abstract

Pneumococcal surface protein A (PspA) is an important virulence factor of Streptococcus pneumoniae. PspA exists as two major families, which include variable but serologically cross-reactive proteins. Previous studies with a family 1 PspA antigen suggested that children develop low concentrations of anti-PspA after pneumococcal carriage or infection. In this study, antibody to PspA families 1 and 2 was measured by an enzyme immunoassay of the serum and saliva of children with a history of culture-proven pneumococcal colonization and/or acute otitis media and in the serum and saliva of adults. The PspA families of the pneumococcal strains isolated from children were determined. The majority of the children had high serum and salivary anti-PspA concentrations to the PspA family they had encountered and low concentrations to the other, whereas adults had high antibody concentrations to both PspA families, both in serum and in saliva. The results suggest that children have a relatively family-specific antibody response to the PspA family they have been exposed to and that any PspA vaccine for children should contain members of both major PspA families.

FIG. 1.

Numbers of subjects and samples selected for the study from among the whole cohort of 329 children and adults participating in the FinOM Cohort Study. The adult saliva samples were from donors not enrolled in the FinOM Cohort Study.

FIG. 2.

Anti-PspA antibodies in the sera of children (47 sera) with previous culture-proven pneumococcal exposures (nasopharyngeal or middle-ear isolates) and in the sera of adults (60 sera). The samples are distributed below and above the limits of detection in the four fields (0.22 μg/ml for PspA1 and 0.26 μg/ml for PspA2), and the number of samples in each of the four sections is given.

FIG. 3.

Salivary antibodies to PspA in children with recent pneumococcal exposures (n = 19) and in 12 adults. Only one sample per child was included in the comparison; the last sample was preceded by exposures to strains with either family 1 (n = 6) or family 2 PspAs (n = 13). Detection limits are indicated in the figures; samples with an OD of <0.04 remain beyond the antibody detection range; samples below that OD are assigned a common OD value equal to half of the detection limit (OD = 0.02).

FIG. 4.

Kinetics of serum anti-PspA1 and -PspA2 antibody development in individual children. The circles indicate positive pneumococcal cultures, and the squares indicate the kinetics of antibodies to either PspA1 or PspA2. The children were divided into three groups based on the pattern of their serum anti-PspA antibody kinetics. Two representatives of each group are shown: PspA family-specific response (A and B), antibody responses to both PspA families in spite of exposure to only one PspA family (C and D), and no anti-PspA response in spite of exposure (E and F). Half of the children had an antibody response specific to the PspA family they had been exposed to (A and B). A simultaneous increase in both anti-PspA1 and -PspA2 concentrations was found in one-fifth of the children who had been exposed to only one of the PspA families (C and D). Acquisition of a strain with a different capsular serotype is indicated in panel D. One-fifth of the children had antibody concentrations below the detection limit (E), or they did not have any response to the PspA that was found in the isolated pneumococci (F).