The Humoral Immune Profiles of Infants Before and After Severe Primary RSV/A and RSV/B Infection

Abstract Introduction Infants are at risk of severe respiratory syncytial virus (RSV) infection. We characterized the humoral immune response of infants with primary RSV infection. Methods Term infants hospitalized for RSV-acute respiratory infection (ARI) or non-RSV–ARI (controls) were enrolled from November 2018 through March 2020 at 5 pediatric medical institutions. Adult controls were women aged 18-45 years without acute RSV infection. Acute and convalescent sera were tested for homologous and heterologous neutralizing antibodies (NtAbs), competitive antibodies (CA) to sites Ø, II, IV and I on the fusion (F) glycoprotein, and anti-postF and 27 amino acid peptide (p27) IgG. Geometric mean titer or CA concentration of acute and convalescent sera were compared between and within groups. Results Sixty-six infants (49 RSV infected and 17 controls) were enrolled. Median age was 76 (IQR 45-179) and 151 (IQR 72-207) days for RSV and control groups, respectively. NtAbs and CA at hospitalization were low among infant groups. Post-infection, RSV/A induced robust homologous and heterologous NtAb responses while RSV/B caused a robust NtAb response only to RSV/B. RSV/A infection generated significant CA rise to sites IV and II, while RSV/B infection resulted in only site II CA rise. Rises in postF and p27 IgG were not detected. Post-infection RSV antibody levels in infants were markedly lower compared to control adult women. Conclusion RSV-infected infants had low pre-infection levels of protective antibodies. Infants infected with RSV/A compared to RSV/B generated a more robust NtAb response, highlighted by a broader CA response to sites II and IV.