NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals

Angélica Cuapio ,C I Edvard Smith,Niklas K Björkström,Gunnar Söderdahl,David Wullimann,Margaret Sällberg Chen,Karin Loré,Anders Österborg,André Pérez Potti,Yu Gao,Marcus Buggert,Mira Akber,Katie Healy,Caroline Boulouis,Giorgio Gabarrini,Jagadeeswara Rao Muvva,Peter Bergman,Olga Rivera‐Ballesteros ,Tobias Kammann,John R Lange ,Per Ljungman,Benedikt Strunz,Soo Aleman,Sandra Muschiol,Ola Blennow,Piotr Nowak,Lotta Hansson,Iva Filipovic,Gordana Bogdanović ,Evren Alici,Michał J Sobkowiak ,Stephan Mielke,Puran Chen,Johan K Sandberg,Fredrika Hellgren,Quirin Hammer,Tiphaine Parrot,Hans‐Gustaf Ljunggren

doi:10.1186/s10020-022-00443-2

Angélica Cuapio , C I Edvard Smith + Show 36 more

Open Access

https://doi.org/10.1186/s10020-022-00443-2

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Abstract

Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021–000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1.

Highlights

COVID-19 vaccination programs have targeted more than 60% of the global population
natural killer (NK) cell absolute counts, frequencies, subsets and phenotypes following BNT162b2 Messenger ribonucleic acid (mRNA) vaccination in healthy individuals and immunocompromised patients In exploratory studies connected to the COVAXID BNT162b2 mRNA clinical trial (Bergman et al 2021), we assessed total NK cells and their subsets in terms of absolute counts and frequencies, and cell phenotypes associated with effector function, activation, maturation, migration and differentiation before and after mRNA vaccination in healthy individuals and patients with primary and secondary immunodeficiencies (Fig. 1A; see Additional file 2: Fig. S1 for complete gating strategy)
As expected due to differences in disease background or intervention combined with specific immunosuppressive treatment, NK cell absolute counts and frequencies differed among the group of healthy individuals and some of the patient groups (Fig. 1C–E)

Summary

Introduction

COVID-19 vaccination programs have targeted more than 60% of the global population (https://ourworldindata.org/covid-vaccinations). This achievement has been the result of major efforts by individual scientists and industries, successful outcomes of clinical trials, and Cuapio et al Molecular Medicine (2022) 28:20 subsequent global vaccination programs. They have been demonstrated to contribute to the regulation of vaccine-elicited T cell and B cell responses (Wagstaffe et al 2018; Cox et al 2021). NK cells isolated from healthy individuals are used as therapeutic agents in clinical trials involving human malignant (Ljunggren and Malmberg 2007; Myers and Miller 2021) and viral diseases including COVID-19 (Market et al 2020; Soleimanian and Yaghobi 2020)

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