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Relevance and heterogeneity of adaptive NK cells in the scenario of SARS-CoV-2: between vaccination and natural infection / A. Frigo, S. Terzoli, M. Calvi, N. Coianiz, F. Calcaterra, C. DI VITO, D. Mavilio. ((Intervento presentato al 14. convegno National SIICA Congress : 22-25 may tenutosi a Verona nel 2023.

Relevance and heterogeneity of adaptive NK cells in the scenario of SARS-CoV-2: between vaccination and natural infection

A. Frigo;M. Calvi;F. Calcaterra;C. DI VITO;D. Mavilio
2023
2023
The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic urged for the rapid development of strategies to immunize the population and simultaneously limit the onset of the severe form of the disease. Since their introduction, SARS-CoV-2 mRNA vaccines revolutionized the branch of vaccinology, given their unique properties as safety, efficacy and rapidity of development. Specifically, formulations such as the Pfizer-BioNTech mRNA vaccine BNT162b2 (Comirnaty) are proven to stimulate a robust humoral response to the SARS-CoV-2 Spike protein, thus conferring a great protection against the natural infection. Nonetheless, adaptive responses induced upon vaccination tend to decline naturally after few months. Still, vaccinated individuals are shielded from the infection and have a reduced probability to develop severe COVID-19 disease, probably due to alternative immune mechanisms. Although poorly understood, non-conventional innate immune responses could be pivotal in conferring the desired long-lasting protection. In this setting, Natural Killer (NK) cells are on trend: beside being typical cytotoxic lymphocytes, essential in controlling viral infections, they are reported to acquire a ”memory-like” phenotype, when stimulated properly. Such adaptive NK cells can mount rapid and more intense cytotoxic responses upon rechallenge. Herein, by means of single-cell RNA sequencing (scRNA-seq) we investigated the effects of the mRNA vaccine BNT162b2 on circulating NK cells in a cohort of six healthy donors, naïve for SARS-CoV2. We were able to identify eight clusters of NK cells, encompassing the major NK cell subsets described in literature. Our data showed that most clusters shared an activated signature, triggered by the first vaccine administration and boosted by the second. This activated signature was accompanied by the upregulation of genes related to adaptive traits, such as CD3E, NKG2C and CD2. Out of all the clusters, the one constituted by adaptive NK cells, showed a peculiar, delayed activation, coherent with the potential of establishing a long-term protection. In line with this hypothesis, we tested the cytotoxic potential of CD2pos memory-like NK cells towards SARS-CoV2 infected Vero cells, in vitro. Preliminary data show that not only the presence of infected cells favors the upregulation of CD2 on NK cells, seemingly pushing toward the adaptive fate, but that CD2pos NK cells of vaccinated subjects also harbor an increased degranulation capacity, as measured by flow cytometry. Last, we inspected the diversity in the repertoire of adaptive NK cells arising after the vaccination and after the natural infection. To this aim, we integrated our data with publicly available scRNA-seq data from non-vaccinated convalescent subjects, recovering from moderate or severe COVID-19. Although sharing the adaptive NK cell signature, cells from the convalescent patients revealed a more heterogeneous situation, possibly reflecting diverse cell states directly related to the natural course of the disease. Collectively, our data highlight a central role for the non-conventional NK cell “memory” in both the vaccine-induced protection and the natural infection. Further investigation is warranted to disclose the actual involvement of adaptive NK cells in controlling SARS-CoV-2 infection.
NK cells; Innate immunity; mRNA vaccine; Innate memory
Settore MEDS-26/A - Scienze tecniche di medicina di laboratorio
Società Italiana di Immunologia, Immunologia Clinica e Allergologia (SIICA)
https://siica.it/siica-xiv-national-congress-2023-siica2023/
Relevance and heterogeneity of adaptive NK cells in the scenario of SARS-CoV-2: between vaccination and natural infection / A. Frigo, S. Terzoli, M. Calvi, N. Coianiz, F. Calcaterra, C. DI VITO, D. Mavilio. ((Intervento presentato al 14. convegno National SIICA Congress : 22-25 may tenutosi a Verona nel 2023.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1144559
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