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T cells prevent severe disease progression even after first vaccination / Antibodies only provide reliable protection against infection after second vaccination dose / Research results published in Nature

In view of the continuing high number of infections worldwide, vaccination offers important protection against severe COVID-19 disease. Scientists from the Faculty of Medicine - University of Freiburg have now been able to break down in detail when initial immune protection can be detected after vaccination with an mRNA-based vaccine and how the reactions of the different components of the human immune system develop over months. The researchers published their results in the online edition of the renowned journal Nature on July 28, 2021.

"Effective protection against severe disease progression is already in place ten days after the first vaccine dose. At this point, however, neutralizing antibodies that prevent the virus from entering the cells are barely detectable. Instead, this early protective effect is due to specific T cells that control the cellular immune response," said Dr. Maike Hofmann, head of a research group in the Department of Medicine II at the Medical Center - University of Freiburg.

Detailed analysis of the immune response

The scientists examined blood samples from 32 test subjects before the first COVID-19 vaccination dose and continuously for up to four months after the second vaccination dose at intervals of three to four days. This allowed them to follow the development of the different components of the immune response in detail. "In the majority of our test subjects, a relevant increase in so-called CD8+ T cells, which are precisely tailored to the SARS-CoV-2-typical spike protein, could already be detected six to eight days after the first vaccination," reports Prof. Dr. Christoph Neumann-Haefelin, Head of the Gerok Liver Center at the Medical Center - University of Freiburg.

After the second vaccination dose, the number of CD8+ T cells increased. It was only at this point that neutralizing antibodies could be detected in such large quantities that they could prevent the virus from penetrating and thus the infection itself. "Our results therefore also underline the importance of complete vaccination with two doses of the mRNA vaccine for good protection against infection," adds Neumann-Haefelin.

High effectiveness of mRNA vaccination technology

The effective combination of rapid T-cell response and neutralizing antibodies is proof of the high efficacy of the still new mRNA vaccination technology. Follow-up studies will show how long the protection lasts after the second vaccination dose and when a booster vaccination - possibly adapted to new virus variants - will be necessary. "The better we understand the mode of action of the mRNA vaccine, the sooner we can develop it further for other diseases - for example for a future vaccination against hepatitis C or a therapeutic vaccination for tumor diseases," explains Prof. Dr. Robert Thimme, Medical Director of the Department of Medicine II at the Medical Center - University of Freiburg.

"The fact that important insights into the development of a solid immune response to SARS-CoV-2 could be gained and published within just a few months demonstrates the great expertise and commitment of our researchers," says Prof. Dr. Lutz Hein, Dean of the Faculty of Medicine - University of Freiburg.

Original title of the study: Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine
DOI: 10.1038/s41586-021-03841-4
Link to the study: www.nature.com/articles/s41586-021-03841-4

Contact:
Prof. Dr. Robert Thimme, Medical Director
Prof. Dr. Christoph Neumann-Haefelin, Head of Gerok Liver Center
Dr. Maike Hofmann, Research Group Leader
Department of Medicine II
Medical Center - University of Freiburg
robert.thimme@uniklinik-freiburg.de
christoph.neumann-haefelin@uniklinik-freiburg.de
maike.hofmann@uniklinik-freiburg.de