Comparative Assessment of Sera from Individuals after S-Gene RNA-Based SARS-CoV-2 Vaccination with Spike-Protein-Based and Nucleocapsid-Based Serological Assays

Abstract

Due to the beginning of vaccination against COVID-19, serological discrimination between vaccine-associated humoral response and serology-based surveillance of natural SARS-CoV-2 infections as well as breakthrough infections becomes an issue of relevance. Here, we assessed the differentiated effects of the application of an RNA vaccine using SARS-CoV-2 spike protein epitopes on the results of both anti-spike protein–based serology (EUROIMMUN) and anti-nucleocapsid-based serology (VIROTECH). A total of 80 serum samples from vaccinees acquired at different time points after vaccination was assessed. While positive or borderline serological response in the anti-spike protein assay was observed for all samples (90% both IgG and IgA, 6.3% IgA only, 3.8% borderline IgG only), only a single case of a falsely positive IgM was observed for the anti-nucleocapsid assay as expected due to this assay’s specificity. Positive anti-spike protein antibodies were already detectable in the second week after the first dose of vaccination, with higher titers after the second dose of the vaccine. In conclusion, the combined application of anti-spike protein–based serology and anti-nucleocapsid-based serology will provide a useful option for the discrimination of vaccination response and natural infection.

Anti-SARS-CoV-2 Receptor-Binding Domain Total Antibodies Response in Seropositive and Seronegative Healthcare Workers Undergoing COVID-19 mRNA BNT162b2 Vaccination

“…Overall, the identification of three important predictors (age, sex, baseline serostatus) of post-COVID-19 mRNA BNT162b2 vaccine humoral response in our population of healthcare workers may have some substantial implications and consequences for vaccine plans. Unlike the recent study of Dörschug et al [21], who used a spike protein-based IgG serological immunoassay for monitoring humoral response to COVID-19 mRNA BNT162b2 vaccine and failed to find significant differences between sexes, we found that women had a significantly higher response (between 1.15-1.20-fold higher compared to men) of total anti-SARS-CoV-2 RBD antibodies, especially after the second vaccine dose. This agrees with recent data published by Terpos et al [22], who also found that the anti-Spike-RBD IgGs response was more sustained in female than in male octogenarians after vaccination with Pfizer BNT162b2 mRNA vaccine.…”

SARS-CoV-2 messenger RNA vaccine antibody response and reactogenicity in heart and lung transplant recipients

“…Priming dose responders in the present study assessed with the same assay but in semiquantitative fashion had a median of at least 250 U/mL 28 days after D2, making their antibody response at least as robust as healthy individuals 3 weeks from series completion. Another study of 27 healthy individuals who received one or two doses of SARS-CoV-2 mRNA vaccine reported median results of 3.3 at 19 days post-D1 and 6.1 at 3 days post-D2 using an anti-S1 immunoassay (EUROIMMUN) ( 33 ). Priming dose responders in the present study assessed with the same assay had median results of 2.4 at 20 days and 9.3 at 28 days following D1 and D2, respectively.…”

Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers

“…This agrees with the recent studies of Salvagno et al [ 18 ] and Terpos et al [ 22 ], where the anti-Spike-RBD IgGs response was also observed to be more sustained in females than in males after vaccination with BNT162b2 vaccine. Another study, where the Euroimmun anti-SARS-CoV-2 S1 IgG ELISA assay was used to monitor humoral response to COVID-19 mRNA BNT162b2 vaccine, did not show any statistically significant correlation between the age and sex of the individuals and the immune response caused by the vaccine [ 23 ].…”

“…Studies have consistently reported higher morbidity and mortality of SARS-CoV-2 infection in women and people of older age, excluding children younger than 5 years old that are also vulnerable [ 19 , 20 , 21 ]. However, concerning the impact of age and sex on vaccine efficiency, the data so far are limited and contradictory [ 18 , 22 , 23 , 24 , 25 , 26 , 27 ]. Thus, more experiments should be conducted to determine this relationship.…”