Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination.

BACKGROUND: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. METHODS: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, and avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2-12 weeks following secondary immunization (T2). RESULTS: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p < .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. CONCLUSIONS: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T-cell activation is unlikely to compensate for poor humoral responses.

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

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.

Comparison of Five Serological Assays for the Detection of SARS-CoV-2 Antibodies.

Serological assays can contribute to the estimation of population proportions with previous immunologically relevant contact with the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) virus. In this study, we compared five commercially available diagnostic assays for the diagnostic identification of SARS-CoV-2-specific antibodies. Depending on the assessed immunoglobulin subclass, recorded sensitivity ranged from 17.0% to 81.9% with best results for immunoglobulin G. Specificity with blood donor sera ranged from 90.2% to 100%, with sera from EBV patients it ranged from 84.3% to 100%. Agreement from fair to nearly perfect was recorded depending on the immunoglobulin class between the assays, the with best results being found for immunoglobulin G. Only for this immunoglobulin class was the association between later sample acquisition times (about three weeks after first positive PCR results) and positive serological results in COVID-19 patients confirmed. In conclusion, acceptable and comparable reliability for the assessed immunoglobulin G-specific assays could be shown, while there is still room for improvement regarding the reliability of the assays targeting the other immunoglobulin classes.

Evaluation of the Xiamen AmonMed Biotechnology rapid diagnostic test COVID-19 IgM/IgG test kit (Colloidal gold).

INTRODUCTION: To efficiently monitor the COVID-19 pandemic for surveillance purposes, reliable serological rapid diagnostic tests (RDTs) are desirable for settings where well-established high-throughput bench-top solutions are not available. Here, we have evaluated such an RDT. METHODS: We have assessed the Xiamen AmonMed Biotechnology COVID-19 IgM/IgG test kit (Colloidal gold) and the EUROIMMUN benchtop assay with serum samples from patients with polymerase chain reaction (PCR)-confirmed COVID-19 disease. Samples from patients with Epstein-Barr-virus (EBV) infection and blood donors were used for specificity testing. RESULTS: For the colloid gold rapid test and the EUROIMMUN assay, the study indicated overall sensitivity of 15.2% and 67.4%, respectively, while specificity of 99.0% and 97.9% with the blood donor sera, as well as 100% and 96.8% with the EBV-patients, were observed, respectively. An association of the time period between positive PCR results and serum acquisition with serological test positivity could be observed for the immunologlobulin G subclass of the EUROIMMUN assay only. CONCLUSIONS: In spite of acceptable specificity of the assessed RDT, the detected poor sensitivity leaves room for improvement. The test results remain difficult to interpret and therefore the RDT can currently not be recommended for routine diagnostic or surveillance use.