In order to investigate the dynamics of the immune response, the scientists carried out comprehensive immunological and viral load analyses of swabs from the nasopharynx and blood samples taken from unvaccinated infected people during the first coronavirus wave. "It is important that we were able to recruit the majority of our test subjects in the first week after the onset of symptoms, i.e. at a very early stage of the infection," says Geldmacher.
This showed that certain inflammatory markers in the blood reached their highest values during the first week after the onset of symptoms - and the higher the viral load in the upper respiratory tract, the higher the values. At the same time, the researchers found evidence of the onset of the immune defense: "Antibodies against the virus are usually not yet present in the first week, but the majority of the test subjects already showed virus-specific activation of T cells," says Geldmacher.
Nucleocapsid-specific T cells inhibit viral replication
In principle, T cells recognized both the envelope protein spike and the viral nucleocapsid, a protein that binds to the RNA of SARS-CoV-2 and forms the main component of the virus in terms of quantity, during this acute infection phase. The nucleocapsid-specific T cells in particular played an important role in the early control of the infection: the more of these cells were present during the first week, the fewer viruses were found in the nasopharynx and the fewer inflammatory markers were found in the blood. This correlation was not detectable for the spike-specific T cells, which are also produced by the SARS-CoV-2 vaccination. In addition, the study results indicate that such activated T cells create an antiviral environment in the infected nasopharyngeal tissue, through which virus-infected cells are better recognized and killed by the immune system.
Taken together, the scientists conclude from their results that the nucleocapsid-specific T cells are central components of the immune defence, which recognize infected and virus-presenting cells with high sensitivity and inhibit the multiplication of the viruses and the associated inflammatory reaction. The researchers explain the fact that these cells correlated much more clearly with the viral load than spike-specific T cells by the fact that both infected cells and the virus itself contain significantly more nucleocapsid than spike - in other words, there is much more material available to activate T cells.
Geldmacher had already made a similar observation in earlier studies with HI viruses, which also contain significantly more nucleocapsid than envelope proteins. "A lot helps a lot," says Geldmacher. Corona vaccines have so far mainly been directed against spike. In light of their results and other independent studies in animal models and humans, the researchers are therefore advocating the inclusion of nucleocapsid proteins in the future in order to develop improved vaccines. This does not only apply to corona: "The inclusion of important T-cell antigens could also improve the effectiveness of other respiratory viruses and make it more difficult for the virus to escape the immune response," emphasizes Geldmacher.
The study was also made possible by the use of existing data sets from published clinical studies. Geldmacher emphasizes: "Access to pseudonymized (double-coded) personal data from published studies for further analyses was of great importance for our study. This also saved us costs of several hundred thousand euros and a lot of effort."
Source: LMU website, 24.05.2023(English version)
