Prefusion F, Postfusion F, G Antibodies, and Disease Severity in Infants and Young Children With Acute Respiratory Syncytial Virus Infection.

ABSTRACT

Background: Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory tract infection in infants. Maternally derived RSV-specific antibodies play a role in protection against RSV infection in early life, but data regarding the concentration and specificity of those antibodies are incomplete. Methods: We prospectively enrolled a cohort of previously healthy infants and young children hospitalized (n = 45) or evaluated as outpatients (n = 20) for RSV infection, and healthy noninfected age-matched controls (n = 18). Serum samples were obtained at enrollment to quantify the concentrations and neutralizing activity of serum immunoglobulin G antibodies to the RSV prefusion (pre-F), postfusion (post-F), and G glycoproteins. We also assessed the associations between antibody concentrations and clinical disease severity. Results: Concentrations of pre-F antibodies were ≥3-fold higher than post-F antibodies and >30-fold higher than G antibodies in serum from infants with acute RSV infection. Antibody concentrations and neutralizing activity inversely correlated with age. The pre-F antibodies displayed the greatest neutralizing activity (55%-100%), followed by G (0%-45%), and post-F (0%-29%) antibodies. Higher concentrations of pre-F and G antibodies, but not post-F antibodies, were associated with lower clinical disease severity scores. Conclusions: Maternal antibodies directed to pre-F, followed by antibodies directed to G, can modulate RSV disease severity in young infants.