Maternal antibodies to pneumolysin but not to pneumococcal surface protein A delay early pneumococcal carriage in high-risk Papua New Guinean infants

Abstract

Immunization of pregnant women can be an efficient strategy to induce early protection in infants in developing countries. Pneumococcal protein-based vaccines may have the capacity to induce pneumococcal serotype-independent protection. To understand the potential of maternal pneumococcal protein-specific antibodies in infants in high-risk areas, we studied the placental transfer of naturally acquired antibodies to pneumolysin (Ply) and pneumococcal surface protein A family 1 and 2 (PspA1 and PspA2) in relation to onset of pneumococcal nasopharyngeal carriage in infants in Papua New Guinea (PNG). In this study, 76% of the infants carried Streptococcus pneumoniae in the upper respiratory tract within the first month of life, at a median age of 19 days. Maternal and cord blood antibody titers to Ply (rho = 0.824, P < 0.001), PspA1 (rho = 0.746, P < 0.001), and PspA2 (rho = 0.631, P < 0.001) were strongly correlated. Maternal pneumococcal carriage (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.25 to 5.39) and younger maternal age (HR, 0.74; 95% CI, 0.54 to 1.00) were independent risk factors for early carriage, while higher cord Ply-specific antibody titers predicted a significantly delayed onset (HR, 0.71; 95% CI, 0.52 to 1.00) and cord PspA1-specific antibodies a significantly younger onset of carriage in PNG infants (HR, 1.57; 95% CI, 1.03 to 2.40). Maternal vaccination with a pneumococcal protein-based vaccine should be considered as a strategy to protect high-risk infants against pneumococcal disease by reducing carriage risks in both mothers and infants.

Figures

FIG. 1.

Pneumococcal nasopharyngeal carriage in PNG mothers according to their age.

FIG. 2.

Maternal pneumococcal carriage as a predictor of age of first pneumococcal carriage in PNG infants. The solid line represents the group of PNG infants whose mothers carried pneumococci at the time of delivery (n = 20), and the broken line represents infants whose mothers were noncarriers (n = 47).

FIG. 3.

Antibody titers to pneumococcal proteins in PNG mothers and newborns and AUS mothers. Data shown are GMTs (and 95% confidence intervals) of antibodies to Ply, PspA1, and PspA2 in plasma samples of Australian mothers (light gray bars; n = 50) and of Papua New Guinean mothers (white bars; n = 87) and their newborns (dark gray bars; n = 89), with * indicating significant differences (P < 0.05) between groups.

FIG. 4.

Cord antibody titers to Ply, PspA1, and PspA2 in relation to early pneumococcal carriage. Data shown are GMTs (and 95% confidence intervals) of antibodies to Ply, PspA1, and PspA2 in cord samples of PNG newborns that carried pneumococci within the first 2 weeks of life (white bars; n = 27), within 2 to 4 weeks of life (gray bars; n = 28), or did not carry within the first 4 weeks of life (black bars; n = 17).