Vaccine- and infection-induced pneumococcal and DENV-NS1 antibodies reveal differential transplacental transfer and maternal–infant early exposure burden

BACKGROUND: Pregnant women and their infants are vulnerable to severe infections with S. pneumoniae and dengue virus (DENV), for which early protection depends on maternally derived antibodies. Infection- and vaccine-induced responses may differ in quality and transfer, with implications for maternal immunization strategies. We evaluated isotype-specific antibody responses to pneumococcal vaccination and natural DENV infection in pregnant women and their infants and quantified early postnatal DENV exposure. METHODS: In a longitudinal cohort in southern Colombia, a DENV-hyperendemic region, 140 low-risk pregnant women received either PPSV23 or Hib conjugate vaccine randomly in the third trimester. Circulating pneumococcal serotype 23F (Pn23F)-specific IgG and DENV NS1-specific IgG, IgM, and IgA were measured by ELISA in maternal, cord, and infant at delivery, 3, and 6 months; circulating NS1 was used to detect active DENV infection. Postnatal clinical follow-up was performed until 6 months of age. RESULTS: PPSV23 increased maternal anti-Pn23F IgG, whereas anti-NS1 IgG from natural infection remained stable. Anti-Pn23F and anti-NS1 IgG were detectable in cord blood, but maternal-cord levels were strongly correlated for anti-NS1 IgG and not for anti-Pn23F IgG. Infant anti-NS1 IgG seropositivity declined from 99% at birth to 74% at 6 months, while anti-Pn23F IgG levels in infants of PPSV23-vaccinated mothers remained stable. Despite 99.1% maternal anti-NS1 IgG seroprevalence, 13.1% of infants developed anti-NS1 IgM or anti-NS1 IgA by 6 months, indicating early DENV infection without NS1 antigenemia or clinically apparent dengue. CONCLUSION: Vaccine- and infection-induced antibodies showed antigen- and isotype-specific differences in transplacental transfer and postnatal persistence, revealing a high burden in the maternal and early infant populations. The emergence of NS1-IgA in infants demonstrates active postnatal DENV transmission and supports NS1-IgA as a sensitive marker for early infant exposure and serosurveillance in hyperendemic settings.