A novel assessment method for COVID-19 humoral immunity duration using serial measurements in naturally infected and vaccinated subjects

Background It is crucial for medical decision-making and vaccination strategies to collect information on sustainability of immune responses after infection or vaccination, and how long-lasting antibodies against SARS-COV-2 could provide a humoral and protective immunity, preventing reinfection with SARS-CoV-2 or its variants. The aim of this study is to present a novel method to quantitatively measure and monitor the diversity of SARS-CoV-2 specific antibody profiles over time. Methods Two collections of serum samples were used in this study: A collection from 20 naturally infected subjects (follow-ups to 1 year) and a collection from 83 subjects vaccinated with one or two doses of Pfizer BioNtech vaccine (BNT162b2/BNT162b2) (follow-ups to 6 months). The Multi-SARS-CoV-2 assay, a multiparameter serology test, developed for the serological confirmation of past-infections was used to determine the reactivity of six different SARS-CoV-2 antigens. For each patient sample, 3 dilutions (1/50, 1/400 and 1/3200) were defined as an optimal set over the six antigens and their respective linear ranges, allowing accurate quantitation of the corresponding six specific antibodies. Nonlinear mixed-effects modelling was applied to convert intensity readings from 3 determined dilutions to a single quantification value for each antibody. Results Median half-life for the 20 naturally infected vs 74 vaccinated subjects (two doses) was respectively 120 vs 50 days for RBD, 127 vs 53 days for S1 and 187 vs 86 days for S2 antibodies. Respectively, 90% of the antibody concentration wanes after 398 vs 158 days for RBD, 420 vs 171 days for S1, and 620 vs 225 days for S2 after the second vaccine shot. Conclusion The newly proposed method, based on a series of a limited number of dilutions, can convert a conventional qualitative assay into a quantitative assay. This conversion helps define the sustainability of specific immune responses against each relevant viral antigen and can help in defining the protection characteristics after an infection or a vaccination.