Newswise — Despite extensive investigation since the onset of the pandemic, the precise involvement of immune system components in early virus replication control within the respiratory tract remains uncertain, thus hindering the prevention of severe cases of COVID-19. Led by PD Dr. Christof Geldmacher, Head of the Infection and Immunity research group at the Division of Infectious Diseases and Tropical Medicine at the LMU University Hospital Munich, a team has successfully demonstrated the significant role played by virus core-targeting immune cells, known as T cells. Published in Nature Communications, these study results have promising implications for enhancing vaccine development.
To explore the immune defense dynamics, the researchers conducted extensive immunological and viral load assessments on swab samples obtained from the nasopharyngeal area (nose and throat) and blood samples from individuals who were not vaccinated and had contracted COVID-19 during the initial phase of the pandemic. "Crucially, we successfully enlisted a majority of our study participants within the initial week of symptom onset, representing a highly early stage of infection," stated Geldmacher.
The analysis conducted by the researchers unveiled that specific markers of inflammation in the bloodstream reached their highest levels within the initial week of symptom onset. There was a direct correlation between the severity of systemic inflammation and the viral load present in the upper respiratory tract. Simultaneously, the team observed early indications of the adaptive immune response targeted at the virus: "Although antibodies targeting the virus were typically absent during the first week, a majority of individuals already displayed virus-specific activation of T cells," Geldmacher explained.
Nucleocapsid-specific T cells inhibit propagation of viruses
During the acute phase, T cells exhibited recognition of both the spike envelope protein and the viral nucleocapsid, a protein responsible for binding to the RNA of SARS-CoV-2 and representing a significant proportion of the virus's protein content. Notably, T cells specific to the nucleocapsid protein seemed to play a crucial role in the early containment of the infection. A higher presence of these cells in the first week correlated with reduced virus detection in the upper respiratory tract and fewer inflammation markers in the bloodstream. However, no such correlation was observed for spike-specific T cells, which are also induced by SARS-CoV-2 vaccination. Additionally, the study findings suggest that these activated T cells establish an antiviral environment within the infected nasopharyngeal tissue, enhancing the immune system's ability to identify and eliminate virus-infected cells.
Geldmacher's earlier studies on the Human Immunodeficiency Virus (HIV), which shares a similar characteristic of having a higher abundance of nucleocapsid compared to envelope proteins, have led him to make a comparable observation. He explains that the viral nucleocapsid gene is less prone to accumulating immune-evading mutations in comparison to spike proteins or HIV envelope proteins. Historically, coronavirus vaccines have predominantly targeted the spike protein. However, based on their findings and additional independent studies conducted on animal models and humans, the researchers argue for the consideration of nucleocapsid proteins in the development of more effective vaccines. This recommendation extends beyond COVID-19, as Geldmacher emphasizes that including crucial T cell antigens in vaccines for other respiratory viruses could enhance their efficacy, make it more challenging for the virus to evade the immune response, and potentially reduce onward transmission even in cases of breakthrough infections following vaccination.
The study's progress was aided by the utilization of preexisting datasets from published clinical trials. Geldmacher highlights the significance of having open access to these pseudonymized (double-coded) data, as it allowed for further analysis in their study. This not only resulted in substantial cost savings, estimated in the hundreds of thousands of euros, but also saved significant labor resources. Such access to data from published studies proved to be highly valuable for the researchers in conducting their study.
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