Vaccines have played a critical role in reducing morbidity and mortality caused by SARS-CoV-2. However, the emergence of new virus variants that can evade the antibody response raises questions about the long-term effectiveness of this strategy. The study was published in the renowned specialist journal natural immunology, opens new perspectives for understanding the immune response against the virus and highlights the fundamental role of T lymphocytes as a long-lasting defense weapon in our body, going beyond the antibody-mediated response.

I study

The researchers used several mouse models, including mice without antibodies but with intact lymphocyte function and an innovative model that expressed a hybrid human/mouse ACE2 receptor. The study was coordinated by Professor Matteo Iannacone, Director of the Department of Immunology, Transplantation and Infectious Diseases of the IRCCS San Raffaele Hospital and Professor of General Pathology at the University Vita-Salute San Raffaele, and in collaboration with Professors Luca Guidotti, Deputy Scientific Director and Professor of General Pathology at IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Marco Bianchi, Head of the Division of Chromatin Dynamics at IRCCS San Raffaele Hospital and Professor of Molecular Biology at Vita-Salute University San Raffaele, and Raffaele De Francesco, Head of the Virology Laboratory at the National Institute of Molecular Genetics and Professor of Microbiology at the University of Milan.

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The immune system

When our immune system is affected by an infection, it uses various defense mechanisms, including the activation of B lymphocytes, which are responsible for the production of antibodies, and the activation of T lymphocytes, which coordinate the entire immune system and act as “foreign” identified cells therefore defeat potentially harmful.

“Our research has shown that T lymphocytes, due to their historical memory, are able to provide protection against the SARS-CoV-2 virus even in the absence of antibodies. This antibody-independent form of defense underlines the crucial importance of the “T cell-mediated cellular response in the fight against the virus,” says the professor Matteo Iannacone.

“We observed that a specific subset of T lymphocytes, called CD8+, is crucial in fighting severe infections, while the so-called CD4+ T lymphocytes play a complementary role in milder infections, with interferon-gamma (IFN-) plays an important role. ),” adds Valeria Fumagalli, researcher in Iannacone’s laboratory, first author of the study and recipient of specific funding from the Prossimo Mio Foundation in Milan.

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Defend against Covid

To date, the focus of the defense strategy against SARS-CoV-2 has been primarily on the antibody response, with the assumption that the antibody-mediated response was the main, if not the only, protective mechanism following vaccination or exposure to the virus. “The results of our study change the traditional understanding of immunity and show the importance of including the T cell-mediated immune response in monitoring vaccination responses and in new vaccine development strategies,” emphasizes Professor Iannacone.

The vaccines

“The indication for vaccination remains the fundamental factor in protecting the population from serious disease, and our research shows the effectiveness of this approach in protecting against reinfection by virus variants as well.” “This work highlights the importance of an approach to immunity against SARS-CoV -2, which takes into account both antibody and cellular responses. Our research paves the way for new vaccination and therapeutic strategies for effective and lasting protection against the virus and its emerging variants,” adds Professor Iannacone.

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“The study was possible thanks to the continuous support of the SAME Foundation, a philanthropic institution of the Same Deutz Fahr group from Treviglio,” emphasizes the professor Luca Guidotti. The SAME Foundation has enabled the creation and deployment of BSL3 biosecurity environments – unique of their kind in Italy – at the IRCCS San Raffaele Hospital: “Thanks to the various advanced technologies dedicated to the study of highly dangerous respiratory viruses in mouse models, these environments have worked. “Conducting high-precision research on SARS-CoV-2 was and continues to be possible,” continues Guidotti. Among the innovative research tools used in this project thanks to donations is also an inhalation tower that allows the exhibition of mouse models to virus particles that infect them in a physiological way by exposing them to SARS-CoV-2, which operates at pressure, temperature and humidity is nebulized. “The support of the SAME Foundation is another example of how scientific research in Italy benefits enormously from philanthropic activities with great impact,” concludes Professor Guidotti.