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

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.