Quantification of the IgG antibody response half-life for hybrid immunity to SARS-CoV-2

Background: A firm understanding of SARS-CoV-2 hybrid immunity is crucial for our ongoing efforts to protect people from severe and fatal disease and assess population vulnerability to emerging novel variants. As many components of the immune response are unobserved and complex to investigate, some ambiguities and unanswered questions remain about hybrid immunity to COVID-19, such as the duration of the antibody response in individuals. Methods: To address this, we evaluated longitudinal data that spanned up to 21 months from 53 SARS-CoV-2 naive individuals and 89 SARS-CoV-2 recovered individuals. We further separated individuals according to whether they received an mRNA or non-mRNA vaccine for their primary two-dose vaccinations. A hierarchical Bayesian framework was used to fit the parameters of single-phase exponential decay and bi-phasic exponential decay models to the observed data to estimate the magnitude and half-life of the spike-specific and receptor-binding domain (RBD)-specific IgG responses. Results: Results from both our single-phase and bi-phasic exponential decay models estimate that the median half-life of the spike-specific and RBD-specific IgG response in individuals with hybrid immunity is almost double that of naive individuals who were only vaccinated. Recovered individuals who received an mRNA vaccine for their primary two-dose schedule were estimated to have the longest IgG half-life response in both model results. Through the single-phase exponential decay estimates, recovered mRNA recipients had a median IgG response half-life of 499 days (95% CrI: [404.9, 635.8]) to RBD antigen and 452.6 days (95% CrI: [376.4, 556.3]) to spike antigen. Estimates from the bi-phasic exponential decay model show that recovered individuals who received mRNA vaccinations had a median IgG response half-life of 859.1 days (95% CrI: [685.7, 1095.4]) to spike antigen and 807.8 days (95% CrI: [645.4, 1030.9]) to RBD antigen. Our results show that, across different model assumptions, individuals with hybrid immunity have an IgG response half-life that is considerably greater than that of individuals with only infection- or vaccine-induced immunity. Conclusions: Our work provides important insight into the longevity of the IgG response to SARS-CoV-2 in individuals with hybrid immunity and can guide effective immunisation approaches to maintain and improve population-level protection.