Neutralizing antibodies against Omicron BA.5 among children with infection alone, vaccination alone, and hybrid immunity

Abstract

Objectives: To assess the binding antibody response and strength of neutralization against Omicron BA.5 in serum samples from children with different antigen exposures (infection/vaccination) and hybrid immunity. Methods: This study recruited children aged 5-7 years. All samples were tested for anti-nucleocapsid immunoglobulin (Ig)G, anti-receptor binding domain (RBD) IgG, and total anti-RBD Ig. Neutralizing antibodies (nAbs) against Omicron BA.5 were determined using a focus reduction neutralization test. Results: A total of 196 serum samples from unvaccinated children with infection (n = 57), vaccination alone (n = 71), and hybrid immunity (n = 68). Our results showed that 90% of the samples from children with hybrid immunity, 62.2% from two-dose vaccination, and 48% from Omicron infection alone had detectable nAbs against Omicron BA.5. The highest neutralizing titer was observed in infection plus two-dose vaccination, which reached 6.3-fold increase, whereas nAb titers in two-dose vaccination was comparable to Omicron-infected sera. However, sera from pre-Omicron infection and single-dose vaccination failed to neutralize Omicron BA.5; although, the total anti-RBD Ig were comparable with Omicron-infected sera. Conclusion: This result highlights that hybrid immunity provided cross-reactive antibodies to neutralize Omicron BA.5 compared with either vaccination or infection alone. The finding emphasizes the importance of vaccination in unvaccinated children who are infected with pre-Omicron or Omicron variants.