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Background In mid-December 2020, Israel had started a nationwide mass vaccination campaign against COVID-19. In the first few weeks, medical personnel, elderly citizens and patients with chronic diseases were prioritized. As such, patients with primary and secondary immunodeficiencies were encouraged to receive the vaccine. While the efficacy of RNA-based COVID-19 vaccines was demonstrated in the general population, little is known about their efficacy and safety in patients with Inborn Errors of Immunity (IEI). Objectives To evaluate the humoral and cellular immune response to COVID-19 vaccine in a cohort of IEI patients. Methods 26 adult patients were enrolled, and plasma and peripheral blood mononuclear cells were collected two weeks following the second dose of Pfizer-BioNTech COVID-19 vaccine. Humoral response was evaluated by testing anti-SARS-CoV-2 Spike (S) Receptor Binding Domain (RBD) and anti-Nuclear (N) antibody titers, and evaluation of neutralizing ability by inhibition of RBD:ACE2 binding. Cellular immune response was evaluated by ELISpot, estimating IL2 and IFNγ secretion in response to pooled SARS-CoV-2 S or M peptides. Results Our cohort included 18 patients with predominantly antibody deficiency, 2 with combined immunodeficiency, 3 with immune-dysregulation, and 3 with other genetically defined diagnoses. 22/26 were receiving immunoglobulin replacement therapy. 18/26 developed specific antibody response and 19/26 showed S-peptide specific T-cell response. None of the patients reported significant adverse events. Conclusion Vaccinating IEI patients is safe, and most patients were able to develop vaccine specific antibody response, S-protein specific cellular response or both.

The presence of tumor-infiltrating Natural Killer (NK) within a tumor bed may be indicative of an ongoing immune response toward the tumor. However, many studies have shown that an intense NK infiltration, is associated with advanced disease and may even facilitate cancer development. The exact role of the tumor infiltrating NK cells and the correlation between their presence and poor prognosis remains unclear. Interestingly, during pregnancy high numbers of a specific NK subset, CD56brightCD16dim, are accumulated within first trimester deciduas. These decidual NK (dNK) cells are unique in their gene expression pattern secret angiogenic factors that induce vascular growth. In the present study we demonstrate a significant enrichment of a CD56brighCD16dim NK cells within tumors. These NK cells express several dNK markers including VEGF. Hence, this study adds new insights into the identity of tumor residual NK cells, which has clear implications for the treatment of human cancer.

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