Rapid decline of SARS-CoV-2–specific salivary IgA antibody levels in people with hybrid immunity—data from the STOPCoV study

Hybrid immune individuals who experience an infection after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine series show evidence of salivary anti-spike and anti-receptor binding domain (RBD) IgA antibodies with broad specificity against different variants. It is unclear how long these antibodies persist and whether they offer protection against new SARS-CoV-2 infections. We compared salivary IgA levels to full-length spike protein and its RBD of the ancestral Wuhan SARS-CoV-2 virus and the Omicron BA.1 variant in a subset of persons participating in a longitudinal study of binding antibody responses to vaccination. We assessed the decay rate of the salivary IgA antibodies in those with hybrid immunity. In our heavily vaccinated population, low levels of salivary IgA to RBD and spike was variably detected in vaccine-only immunity to both Wuhan and Omicron BA.1, but antibody levels were an order of magnitude higher in those with hybrid immunity. In hybrid immune individuals, anti-spike/RBD salivary IgA rapidly decayed over a 4-month observation period. In a multivariate analysis, salivary IgA antibody to Omicron BA.1 was not associated with protection from a new SARS-CoV-2 infection over the subsequent 10 months during the Omicron XBB.1.5, EG.5, and JN waves of infection. In contrast, receipt of a new vaccine dose was significantly associated with protection.