Ricerc@Sapienza

We are extending our previous observations on the Impact of vaccination on NK cell compartment. Our study revealed that mRNA based Sars-Cov2 vaccine stably affect NK cell phenotype and functions highlighting the impact of genetic and environmental host-related factors in modulating NK cell susceptibility to post-vaccinal Fc-dependent functional impairment.

Natural Killer (NK) cells contribute to the protective effects of vaccinal antibodies (Abs) thanks to the IgG receptor, FcγRIIIA/CD16, whose aggregation leads to the killing of infected cells and IFNγ release, which potentiates adaptive responses.

We recently focused on the adjuvanted glycoprotein E (gE)-based Recombinant Zoster Vaccine (RZV, Shingrix, GSK) which efficacy in Primary Antibody Deficient (PAD) patients is completely unknown. We have evidence that, while the vast majority of unclassified PAD (unPAD) patients exhibited significant Ab production, a significant portion of Common Variable Immunodeficient (CVID) patients was unable to produce anti-gE IgG. Vaccine-induced Abs were effective in activating gE-specific, CD16-dependent cytotoxicity and cytokine production in NK cells.

Interestingly, the conventional NK pool is selectively exhausted in CVID patients, more markedly in non-responders, in a maturation-dependent fashion. At variance, an expansion of memory NK compartment, endowed with amplified Ab-dependent functions and reduced susceptibility to exhaustion, was selectively observed in CVID patients.

The findings of a perturbation of memory NK cell compartment and reduced inhibitory checkpoints expression levels in conventional NK pool led us to investigate their phenotypic and functional profile in both naive CVID or those undergoing to intravenous immunoglobulin (IVIg) replacement. These studies will provide insights on the pathophysiology of the natural immune system in CVID patients also evidencing as distinct features of memory NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in immunodeficient patients.