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In Italy, from January 2021, the Ministry of Health indicated a vaccination plan against COVID for frail patients and physicians based on a three-dose scheme. However, conflicting results have been reported on which biomarkers permit immunization assessment. We used several laboratory approaches (i.e., antibodies serum levels, flow cytometry analysis, and cytokines release by stimulated cells) to investigate the immune response in a cohort of 53 family pediatricians (FPs) at different times after the vaccine. We observed that the BNT162b2-mRNA vaccine induced a significant increase of specific antibodies after the third (booster) dose; however, the antibody titer was not predictive of the risk of developing the infection in the six months following the booster dose. The antigen stimulation of PBMC cells from subjects vaccinated with the third booster jab induced the increase of the activated T cells (i.e., CD4+ CD154+); the frequency of CD4+ CD154+ TNF-α+ cells, as well as the TNF-α secretion, was not modified, while we observed a trend of increase of IFN-γ secretion. Interestingly, the level of CD8+ IFN-γ+ (independently from antibody titer) was significantly increased after the third dose and predicts the risk of developing the infection in the six months following the booster jab. Such results may impact also other virus vaccinations. [ABSTRACT FROM AUTHOR]

Simple Summary: Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis (PTB), chronic enteritis of ruminants spread worldwide. PTB is, by now, considered a conditioned disease, depending on both environmental and genomic factors. PTB susceptibility seems to be related to some genes coding for immune regulators involved in the cell-mediated response during infection: genetic markers, particularly single nucleotide polymorphisms (SNPs), have been investigated in several studies, and different candidate genes have been highlighted as associated with PTB resistance/susceptibility. The aim of this preliminary study was to verify, for the first time in a local beef cattle breed, known as Marchigiana, an association between MAP infection status and SNPs in candidate immune-genes. Specifically, in a MAP-infected herd, IFN-γ tests, ELISA, qPCR, and cultures were performed, for a follow-up range of 3–6 years, on 112 bovines to evaluate the state of MAP infection. Animals with positive results for at least one test were considered infected. DNA samples of bovines with a known MAP status were analyzed to assess the presence and the genotypic frequency of SNPs in genes encoding for gamma-interferon (BoIFNG), interleukin receptor 10 (IL10RA), interleukin receptor 12 (IL12RB2), and toll-like receptors (TLR1, TLR2, TLR4). For the IL10RA and IL12RB2 genes, relevant differences in genotypic frequencies among the considered cattle groups were observed. For all the investigated candidate genes, SNP genotypes that have been associated with PTB resistance in the literature, were found more frequently, suggesting potential genetic resistance traits in the Marchigiana breed. Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis (PTB), a widespread chronic enteritis of ruminants. The progression of the infection depends on the containment action of innate and cell-mediated immunity (CMI), and it is related to environmental and genetic factors. In particular, PTB susceptibility seems to be associated with specific genes coding for immune regulators involved in the cell-mediated response during the infection. The aim of this preliminary study was to verify, in Italian beef cattle, an association between MAP infectious status and the presence of single nucleotide polymorphisms (SNPs) in candidate genes. To the best of our knowledge, this is the first investigation conducted on a native beef cattle breed, known as Marchigiana, reared in Central Italy. The present research, based on a longitudinal study, aimed to identify and correlate phenotypic and genetic profiles characteristic of the subjects potentially able to contrast or contain PTB. In a MAP-infected herd, ELISA, IFN-γ tests, qPCR, and cultures were performed at a follow-up, occurring within a period ranging from three to six years, to evaluate the individual state of infection. Animals testing positive for at least one test were considered infected. DNA samples of 112 bovines, with known MAP statuses, were analyzed to verify an association with SNPs in the genes encoding gamma-interferon (BoIFNG), interleukin receptor 10 (IL10RA), interleukin receptor 12 (IL12RB2), and toll-like receptors (TLR1, TLR2, TLR4). Regarding statistical analysis, the differences among target genes and pairs of alleles in the analyzed groups of animals, were evaluated at a significance level of p < 0.05. For IL10RA and for IL12RB2 genes, relevant differences in genotypic frequencies among the considered cattle groups were observed. For all candidate genes studied in this investigation, SNP genotypes already associated with PTB resistance were found more frequently in our population, suggesting potential resistance traits in the Marchigiana breed. [ABSTRACT FROM AUTHOR]

The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to Mycobacterium tuberculosis -specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population., (Copyright © 2018 American Society for Microbiology.)

Background: This study aimed to evaluate inducible protein-10 (IP-10) as a biomarker besides interferon-gamma (IFN-γ) to improve the identification of active tuberculosis (TB) and latent tubercular infection (LTBI) in a country with a low incidence of TB., Methods: Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with region-of-difference-1 (RD1)-specific peptides and with heparin-binding hemagglutinin (HBHA) to determine the release of IP-10 and IFN-γ., Results: No statistically significant difference was observed between positive rates of IP-10 and IFN-γ after RD1-specific peptide stimulation in the TB and LTBI groups; a different response was detected in QuantiFERON TB-gold test-negative (QFT-) subjects. A significantly different proportion of positive responses was observed between IP-10 and IFN-γ following HBHA stimulation in the TB group and in the QFT- group but not in the LTBI group., Conclusions: The IP-10 test seemed to identify false-negative QFT results in some subjects with a positive IFN-γ/IP-10/HBHA pattern.