Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination

Abstract

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients—despite a decline in total S-specific antibodies—neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that—compared with mRNA vaccination—natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.

Comparison of the Anti-SARS-CoV-2 Surrogate Neutralization Assays by TECOmedical and DiaPROPH-Med with Samples from Vaccinated and Infected Individuals

“…Further, it was clear that the functionality of adaptive immunological components is more important than just sole quantity [5]. In line with this, it became evident that a diagnostic focus should be on the neutralizing the potency of detected anti-SARS-CoV-2-antibodies [6,7].…”

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

“…Recently, more studies are exploring the efficacy of the natural immune response to SARS-CoV-2 vs. the mRNA vaccine-elicited response [22][23][24][25]. Our most recent work confirmed that following a natural infection, neutralizing antibody (nAbs) titers generated during infection accompanied by vaccination are significantly better in function than those generated by vaccination alone [26]. To this end, in this study, we compared the neutralization capacity of previously infected individuals and healthy previously unexposed individuals before and after vaccination against several variants of concern (VOCs) using a surrogate viral neutralization assay [27].…”

“…There is growing, but still limited, information available on immunity against the viral variants conferred by natural infection with the authentic SARS-CoV-2 strain or by the mRNA COVID-19 vaccines. Using samples collected during the COVID-19 pandemic, most of them before the documented introduction of the variants in the jurisdiction of Puerto Rico [26,28], we attempted to compare the kinetics of the nAbs response in the context of individuals with naturally acquired infection (pre-exposed) and unexposed individuals, following vaccination, via a widely used sVNT detecting RBD-targeting antibodies [26,[29][30][31].…”

“…To determine the neutralizing activity of antibodies against SARS-CoV-2, we used a surrogate viral neutralization test (C-Pass GenScript sVNT, Piscataway, NJ, USA) according to the manufacturer's instructions [13,26,27]. Briefly, serum samples were diluted according to the manufacturer's instructions and incubated with soluble SARS-CoV-2 receptorbinding domain (RBD-HRP; S-RBD-HRP Wild Type (WT), Genscript Cat no.…”

The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization

“…Collectively, Seronet institutions reported development of 27 in-house ELISA methods (Table 1). 6,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] The majority of ELISA methods were developed for testing of serum and/or plasma, with additional methods available for testing dried blood spots (DBS), saliva/oral fluid, and breast milk. Two methods have been granted FDA EUA approval, 3 methods are pending FDA EUA, 4 methods are validated for high-complexity testing in a CLIA-certified laboratory, and 18 methods are for research-use only (RUO).…”