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

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.

Immunological response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis treated with Rituximab

“…First, we showed that, despite the impaired B cells and humoral anti-spike response, the patient under RTX who contracted the SARS-CoV-2 infection mounted a robust innate and CD8-effector memory T cell response. These findings are in agreement with reports showing that B cells are not required for recovering from SARS-CoV-2 in MS patients under immunosuppressants,[ 19 , 20 ] and that, innate and CD8 T cell response are most relevant in fighting SARS-CoV2 infection. [ 21 , 22 ] After vaccination, we found comparable innate and adaptive responses between patients with no circulating B cells and controls, as previously shown in patients with MS under anti-CD20 therapies.…”

“… [10] NK cells increased in RTX patients in accordance with previous reports after mild SARS-Cov2 infection and vaccination in immunocompromised patients. [ 20 , 21 ] One unexpected finding was the lack of IFN-γ production in one of the RTX-treated patients after both infection and vaccinations. Given that T cells from the other RTX patients analysed here produced IFN-γ, this finding may be related to a delayed immune response - not captured at the time points we analysed - rather than to B cell depletion.…”

Cellular and humoral SARS-CoV2 vaccination responses in 192 adult recipients of allogeneic hematopoietic cell transplantation

“…With regard to lymphocyte subsets we were able to con rm previous observations, as in our cohort humoral response correlated with higher B-, NK-as well as CD4-cell count in the vaccination period 9,25,27,30,31 . Intriguingly, cellular response failure in our collective correlated with higher CD8 + and activated, HLA-DR + T cells one year after transplantation.…”

Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications

“…In this context, very recent evidence suggests that the frequency of NKG2C pos NK cells before the vaccination can positively influence the anti-SARS-CoV-2 antibody titers following two doses of BNT162b2 mRNA vaccine ( 121 ). However, by comparing the NK cell responses in subjects receiving two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) and who develop or not COVID-19 after vaccination or subjects experienced for SARS-CoV-2 infection and infused or not with CoronaVac, any differences in terms of IFN- γ release upon overnight stimulation with aspecific NK cell activation stimuli have been observed ( 122 ).…”