Evolution-dependent SARS-CoV-2 vaccination success determined by neutralizing antibodies and reliability of point-of-care testing

SARS-CoV-2 spread from Wuhan in China all over the world and was first detected in February 2020 in Germany. Under biosafety level 3 conditions, we established a Vero cell-based cultivation system and isolated an early Wuhan-like type (wt) of SARS-CoV-2 and the variants of concern Alpha, Delta, Omicron BA.1, and Omicron BA.2. Moreover, we established a Vero cell-based virus neutralization test to validate various diagnostic systems and to estimate vaccination success. Since RT-qPCR tests were not sufficient for mass testing, point-of-care tests (POCTs) for antigen detection became necessary. In 2020, we determined the sensitivity of a newly developed POCT by comparison with RT-qPCR and virus cultivation assays. The accuracy of eight commercial SARS-CoV-2 specific antibody tests were compared to RT-qPCR and neutralization tests. The sensitivities ranged between 80.8 and 96.3 % and the specificities from 96.0 to 100.0 %. Moreover, we defined the sensitivity of two surrogate virus neutralization tests and found that they greatly overestimated the presence of NAs. Two vaccinations were required for high avidity IgGs. We analyzed the humoral and cellular immune response after infection and vaccination and compared various vaccination schemes concerning IgG concentrations and neutralization titers. mRNA-based and heterologous vaccination schedules were superior as compared to homologous vector-based vaccinations. Interferon gamma release by CD8+ T cells was comparable for the different vaccination schemes. The effects of a third vaccination were studied in the context of the Delta variant wave and led to a significant increase in IgG concentrations and Delta neutralization titers. Nucleocapsid protein-specific IgGs had a half-life period of 156 d and spike protein-specific IgGs as well as neutralization titers of more than 165 d. An immune escape was not detectable for the Alpha variant compared to the wt of SARS-CoV-2. In contrast, neutralization titers were considerably lower for the Delta variant, and even more for the Omicron variants BA.1 and BA.2. Infection with Omicron BA.1 did not induce neutralization titers against the Delta variant in individuals without prior immunization. Thus, the Omicron variants represent a new SARS-CoV-2 serotype and demonstrate the need for variant-adjusted vaccines.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Christian-Albrechts-Universität zu Kiel

Year

2026

Author dc:creator

• Rose, Ruben

Contributors dc:contributor

• Fickenscher, Helmut
• Ankermann, Tobias

• SARS-CoV-2
• COVID-19
• neutralizing antibodies
• point-of-care test POCT
• variants of concern
• antibody test
• vaccination success
• immune escape

Repository record source_url

https://macau.uni-kiel.de/receive/macau_mods_00008691

OAI identifier oai:identifier

oai:macau.uni-kiel.de:macau_mods_00008691