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

Abstract

SummaryIn areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high‐risk areas have pre‐existing pneumococcal‐specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA‐induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA‐specific interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐5, IL‐6, IL‐10 and IL‐13 responses, and lower dPly‐IL‐6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA‐IL‐5 and PspA‐IL‐13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly‐IL‐6 responses with a higher frequency of cord antigen‐presenting cells. In the PNG cohort, higher PspA‐specific IL‐5 and IL‐6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA‐IL‐10 CBMC responses. Pneumococcus‐specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.

Pneumococcal conjugate vaccine primes mucosal immune responses to pneumococcal polysaccharide vaccine booster in Papua New Guinean children

“…Secondly, compared to children in low-risk settings, PCV may be more capable of inducing mucosal immune responses in children at high risk of pneumococcal infections, even after or maybe because of our accelerated vaccination schedules. Infants in high-risk settings such as PNG experience early pneumococcal colonization with a broad range of pneumococcal serotypes [6] , [7] , [8] . Possibly this early colonization stimulates the development of mucosal vaccine responses, unlike systemic vaccine responses that reportedly may be suppressed in individuals colonized with vaccine serotypes before vaccination [34] , [35] .…”

“…Pneumococcal colonization is a major risk factor for mucosal and invasive pneumococcal disease [5] . In the highlands of PNG, pneumococcal colonization starts within a few weeks of birth, with half of children being colonized before 3 weeks of age [6] . In addition, the range of colonizing pneumococcal serotypes is broad and more diverse than in low-endemicity settings and children can carry multiple serotypes at the same time [7] , [8] .…”