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 ( ‫؍‬ 0.824, P < 0.001), PspA1 ( ‫؍‬ 0.746, P < 0.001), and PspA2 ( ‫؍‬ 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.

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

“…In settings with a high burden of pneumococcal disease such as PNG, infants become colonized rapidly and disease is likely to follow. For example, in PNG 50% of infants are colonized by 17–18 days of age 5. Moreover, in high‐risk settings pneumococcal colonization is intense, persistent and continues into adulthood.…”

“…We reported recently that in young infants in Papua New Guinea (PNG), a country highly endemic for pneumococcal infections, PspA‐specific antibodies are high at the time of birth and decline during the first 3 months of life, presumably due to waning of maternal antibodies, followed by an increase with ongoing exposure and increasing age 19. In this same study population, higher levels of naturally acquired immunoglobulin (Ig)G antibodies to dPly at birth were associated with delayed pneumococcal colonization during the first month of life; however, the opposite was observed for cord PspA‐specific antibodies 5. A US study, including 11 adults and 17 children (aged 6 months to 3 years), showed that in‐vitro responses to pneumococcal proteins, including PspA and dPly, were dominated by T helper type 1 (Th1) responses [interferon (IFN)‐γ, interleukin (IL)‐2] or primed ‘uncommitted’ (IL‐2) responses in adults, while in children responses were mainly ‘uncommitted’ IL‐2 responses 20.…”

“…The production of the recombinant PspA family 1 (PspA1) and PspA family 2 (PspA2) antigens from S. pneumoniae is outlined in Francis et al . 5. Briefly, PspA1 (family 1, clade 2) was derived from the recombinant PspA/Rx1 AA1…302 protein, which comprised 302 N‐terminal amino acids of the pneumococcal strain Rx1 PspA, and PspA2 (family 2, clade 3) from PspA/V‐24 AA1…410 , consisting of amino acids 1–410 of the wild‐type mature PspA S. pneumoniae Taiwan19F‐14.…”

“…Nasopharyngeal colonization is an immediate precursor to disease 3, 4. In low‐income settings infants become colonized rapidly, with carriage often persisting into adulthood 5. Early onset of pneumococcal carriage is considered an important risk factor for the high burden of serious pneumococcal disease and death in young infants 6, 7, 8, 9.…”

“…In the Eastern Highlands Province (EHP) of PNG, infants are colonized with S. pneumoniae within the first 3 months of life, with a median age of pneumococcal acquisition of 17–18 days 5, 24. In comparison, in a high‐income country such as Australia, fewer than half of non‐Indigenous Australian children carry pneumococci at least once during their first year of life 25.…”