Harmonization of six quantitative SARS-CoV-2 serological assays using sera of vaccinated subjects

• Published in: Clinica chimica acta Vol. 522; pp. 144 - 151
• Main Authors: Ferrari, Davide, Clementi, Nicola, Spanò, Sestina Maria, Albitar-Nehme, Sami, Ranno, Stefania, Colombini, Alessandra, Criscuolo, Elena, Di Resta, Chiara, Tomaiuolo, Rossella, Viganó, Marco, Mancini, Nicasio, De Vecchi, Elena, Locatelli, Massimo, Mangia, Alessandra, Perno, Carlo Federico, Banfi, Giuseppe
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2021
• Subjects: Comirnaty vaccine; COVID-19; Neutralization; SARS-CoV-2; Serological standard; WHO; COVID-19; SARS-CoV-2; Serological standard; Comirnaty vaccine; WHO; Neutralization
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2021.08.024

•An accessible and highly concentrated working standard specific for IgG against SARS-CoV-2 Spike-protein was prepared.•The serological SARS-CoV-2 WHO International Standard behaves differently from the working standard produced using sera from vaccinated subjects.•A single instrument-to-instrument conversion factors is not sufficient to harmonize different instruments readouts from single samples.•The devices tested performed well in predicting neutralization activity based on the antibody titer. Vaccines, to limit SARS-CoV-2 infection, were produced and reliable assays are needed for their evaluation. The WHO produced an International-Standard (WHO-IS) to facilitate the standardization/comparison of serological methods. The WHO-IS, produced in limited amount, was never tested for reproducibility. This study aims at developing a reproducible and accessible working standard (WS) to complement the WHO-IS. Sera from vaccinated individuals were used to produce the WSs. The WHO-IS, the WSs and single serum samples (n = 48) were tested on 6 quantitative serological devices. Neutralization assays were performed for the 48 samples and compared with their antibody titers. The WS carry an antibody titer 20-fold higher than the WHO-IS. It was reproducible, showed both good linearity and insignificant intra- and inter-laboratory variability. However, the WSs behave differently from the WHO-IS. Analysis of the 48 samples showed that single correlation factors are not sufficient to harmonize results from different assays. Yet, all the devices predict neutralization activity based on the antibody titer. A reproducible and highly concentrated WS, specific for IgG against SARS-CoV-2 Spike-glycoprotein was produced. Such characteristics make it particularly suited for the harmonization of commercially available assays and the consequent evaluation of post-vaccinated individuals.