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RSV neutralizing antibodies at birth predict protection from RSV illness in infants in the first three months of life

Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of viral pneumonia and bronchiolitis during the first six months of life. Placentally-transferred antibodies can prevent severe RSV illness, and maternal immunization may reduce illness in young infants. Identifying protective antibody levels will facilitate the advancement of vaccine candidates and maternal immunization. Methods: We conducted a nested case-control study involving 587 Malian mother-infant pairs, followed from birth to 6 months of age. RSV cases were infants who developed influenza-like-illness (ILI) or pneumonia and were RSV positive by PCR. Cases were matched to healthy controls and RSV-negative ILI controls. RSV-A and RSV-B neutralizing antibodies were measured in maternal, cord blood, and infant sera at 3 and 6 months of age. Results: Maternal antibodies were efficiently transferred to infants. Maternal and infant RSV titers were strongly correlated. Infant antibody titers against RSV-A were 3X higher compared to those against RSV B. At birth, infants who remained healthy had significantly higher RSV-A and RSV-B titers compared to infants that subsequently contracted RSV. RSV-A IC80 titer >239 or RSV-B IC80 titer >60 at birth was significantly associated with being a healthy control compared to an RSV case within the first three months of life. RSV-A IC80 titers in cord blood were associated with decreased episodes of pneumonia. Conclusions: Maternally acquired RSV antibodies were associated with protection of infants against community-detected cases of RSV-ILI and pneumonia. RSV antibody levels in cord blood can predict whether an infant will be infected with RSV or remain uninfected.

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