Cellular and humoral immune response to SARS-CoV-2 mRNA vaccines in patients treated with either Ibrutinib or Rituximab.

Patients treated with B-cell-targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison with the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection.

Peroxidase profiling reveals genetic linkage between peroxidase gene clusters and basal host and non-host resistance to rusts and mildew in barley.

BACKGROUND: Higher plants possess a large multigene family encoding secreted class III peroxidase (Prx) proteins. Peroxidases appear to be associated with plant disease resistance based on observations of induction during disease challenge and the presence or absence of isozymes in resistant vs susceptible varieties. Despite these associations, there is no evidence that allelic variation of peroxidases directly determines levels of disease resistance. METHODOLOGY/PRINCIPAL FINDINGS: The current study introduces a new strategy called Prx-Profiling. We showed that with this strategy a large number of peroxidase genes can be mapped on the barley genome. In order to obtain an estimate of the total number of Prx clusters we followed a re-sampling procedure, which indicated that the barley genome contains about 40 peroxidase gene clusters. We examined the association between the Prxs mapped and the QTLs for resistance of barley to homologous and heterologous rusts, and to the barley powdery mildew fungus. We report that 61% of the QTLs for partial resistance to P. hordei, 61% of the QTLs for resistance to B. graminis and 47% of the QTLs for non-host resistance to other Puccinia species co-localize with Prx based markers. CONCLUSIONS/SIGNIFICANCE: We conclude that Prx-Profiling was effective in finding the genetic location of Prx genes on the barley genome. The finding that QTLs for basal resistance to rusts and powdery mildew fungi tend to co-locate with Prx clusters provides a base for exploring the functional role of Prx-related genes in determining natural differences in levels of basal resistance.

Isolate specificity of quantitative trait loci for partial resistance of barley to Puccinia hordei confirmed in mapping populations and near-isogenic lines.

Partial resistance is considered race-nonspecific and durable, consistent with the concept of 'horizontal' resistance. However, detailed observations of partial resistance to leaf rust (Puccinia hordei) in barley (Hordeum vulgare) revealed small cultivar x isolate interactions, suggesting a minor-gene-for-minor-gene interaction model, similar to so-called 'vertical' resistance. Three consistent quantitative trait loci (QTLs), labelled Rphq2, Rphq3 and Rphq4, that were detected in the cross susceptible L94 x partially resistant Vada have been incorporated into the L94 background to obtain near-isogenic lines (NILs). Three isolates were used to map QTLs on seedlings of the L94 x Vada population and to evaluate the effect of each QTL on adult plants of the respective NILs under field conditions. Rphq2 had a strong effect in seedlings but almost no effect in adult plants, while Rphq3 was effective in seedlings and in adult plants against all three isolates. However, Rphq4 was effective in seedlings and in adult plants against two isolates but ineffective in both development stages against the third, demonstrating a clear and reproducible isolate-specific effect. The resistance governed by the three QTLs was not associated with a hypersensitive reaction. Those results confirm the minor-gene-for-minor-gene model suggesting specific interactions between QTLs for partial resistance and P. hordei isolates.