Electronic Package Leaflets for Vaccines: What Are People's Perceptions in Italy?

In Italy, the paper package leaflet (PPL) is the official document that is approved by the Italian Medicines Agency (AIFA) for each medicine. PPLs of all medicines, including vaccines, are freely available online by accessing the AIFA website. To investigate people's attitudes toward possible access to the PPLs of vaccines and the acceptability of switching to an electronic package leaflet (e-leaflet) in the future, we surveyed three target groups (pregnant women, young parents, and older people) in Italy, via an online survey. We collected 321 questionnaires from the cohorts, which comprised 104 pregnant women, 105 young parents, and 112 older people. The results indicate in all target groups that health care professionals (HCPs) do not usually offer the vaccine PPL during the vaccination session: only about 10.7% of respondents receive the PPL without asking for it, with pregnant women receiving it the most frequently. The acceptance rate for switching from a PPL to an e-leaflet is fairly high in all target groups (76.9% in pregnant women, 81.9% in young parents, and 66.1% in the elderly), especially if the option exists to request a paper print, to make sure that people with a low level of digital skills can access the PPL information as well. HCPs have an important role in ensuring access to the PPLs of vaccines. HCPs should be trained to inform their patients about the different options for accessing the PPLs (as well as online access) to increase their patients' knowledge and satisfaction.

Replacing vaccine paper package inserts: a multi-country questionnaire study on the acceptability of an electronic replacement in different target groups.

BACKGROUND: In the European Union it is mandatory to include paper package leaflets (PPL) with all medicines, including vaccines, to inform the recipient. However, it is difficult to meet the necessity for localized PPLs in each of the 24 official European languages. Replacing PPLs with electronic versions offers many advantages including redistribution across nations, reduced storage space, accessibility by the visually impaired, easily updated information or the addition of video content. We wanted to assess the attitudes of patients (vaccine recipients or their parents) to the potential of replacing PPL with electronic versions. METHODS: We surveyed vaccinees or their parents in four European countries-Belgium, Italy, Bulgaria and France-for their actual use of vaccine PPLs and their opinions about switching to an electronic package leaflet. Our survey was conducted online because of the COVID-19 pandemic and resulted in 2518 responses to a questionnaire targeted at three specific groups with particular information needs: parents of young children, pregnant women and the elderly (≥ 60 years). RESULTS: Our main findings are that currently vaccine PPLs are rarely used and frequently unavailable for the vaccinee. Across the four countries surveyed 55-82% of vaccinees would accept an electronic version, as did 64% when there was an option to request a printout of the leaflet. CONCLUSIONS: We found that switching to electronic versions of vaccine PPLs is an acceptable alternative for the public, potentially increasing the quality and amount of information reaching vaccinees while eliminating some barriers to redistribution of vaccines between countries.

A new pathway of CD5 glycoprotein-mediated T cell inhibition dependent on inhibitory phosphorylation of Fyn kinase.

Triggering of the T cell receptor initiates a signaling cascade resulting in the activation of the T cell. These signals are integrated alongside those resulting from the triggering of other receptors whose function is to modulate the overall response. CD5 is an immunotyrosine-based inhibition motif-bearing receptor that antagonizes the overt T cell receptor activation response by recruiting inhibitory intracellular mediators such as SHP-1, RasGAP, or Cbl. We now propose that the inhibitory effects of CD5 are also mediated by a parallel pathway that functions at the level of inhibition of Fyn, a kinase generally associated with T cell receptor-mediated activation. After CD5 ligation, phosphorylation of the negative regulatory tyrosine (Tyr(531)) of Fyn increases, and this correlates with a substantial reduction in the kinase activity of Fyn and a profound inhibition of ZAP-70 activation. The effect requires the last 23 amino acids of the cytoplasmic domain of the receptor, strongly implying the involvement of a new CD5-interacting signaling or adaptor protein. Furthermore, we show that upon CD5 ligation there is a profound shift in its distribution from the bulk fluid phase to the lipid raft environment, where it associates with Fyn, Lck, and PAG. We suggest that the relocation of CD5, which we also show is capable of forming homodimers, to the proximity of raft-resident molecules enables CD5 to inhibit membrane proximal signaling by controlling the phosphorylation and activity of Fyn, possibly by interfering with the disassembly of C-terminal Src kinase (Csk)-PAG-Fyn complexes during T cell activation.

Protein interactions between CD2 and Lck are required for the lipid raft distribution of CD2.

In T lymphocytes, lipid rafts are preferred sites for signal transduction initiation and amplification. Many cell membrane receptors, such as the TCR, coreceptors, and accessory molecules associate within these microdomains upon cell activation. However, it is still unclear in most cases whether these receptors interact with rafts through lipid-based amino acid modifications or whether raft insertion is driven by protein-protein interactions. In murine T cells, a significant fraction of CD2 associates with membrane lipid rafts. We have addressed the mechanisms that control the localization of rat CD2 at the plasma membrane, and its redistribution within lipid rafts induced upon activation. Following incubation of rat CD2-expressing cells with radioactive-labeled palmitic acid, or using CD2 mutants with Cys226 and Cys228 replaced by alanine residues, we found no evidence that rat CD2 was subjected to lipid modifications that could favor the translocation to lipid rafts, discarding palmitoylation as the principal mechanism for raft addressing. In contrast, using Jurkat cells expressing different CD2 and Lck mutants, we show that the association of CD2 with the rafts fully correlates with CD2 capacity to bind to Lck. As CD2 physically interacts with both Lck and Fyn, preferentially inside lipid rafts, and reflecting the increase of CD2 in lipid rafts following activation, CD2 can mediate the interaction between the two kinases and the consequent boost in kinase activity in lipid rafts.

MDM2 is recognized as a tumor-associated antigen in chronic lymphocytic leukemia by CD8+ autologous T lymphocytes.

OBJECTIVE: Tumor-associated antigens (TAA) are the basis for antigen-specific immunotherapy. The human homolog of the murine double-minute 2 oncoprotein (MDM2) is a putative TAA because it is overexpressed in several malignancies, including chronic lymphocytic leukemia (CLL) cells compared with normal B lymphocytes. PATIENTS AND METHODS: Autologous, MDM2-specific human leukocyte antigen (HLA)-A2-restricted T cells were identified using interferon (IFN)-gamma-ELISPOT assays and HLA-A2/dimer-peptide staining after 4 weeks of in vitro culture. RESULTS: Using native CLL cells as antigen-presenting cells (APCs), we demonstrate the generation of MDM2-specific T cells in 7/12 CLL patients that recognized specifically the MDM2-derived peptide MDM2(81-88) bound to HLA-A2-dimers while they were inactive against an unrelated MAGE-3 peptide (p = 0.002). After 4 weeks, up to 32.3% of the expanded CD8(+) T cells specifically recognized MDM2(81-88) by HLA-A2-dimer/peptide staining and up to 0.9% of all T cells expanded reacted specifically against this MDM2-derived peptide in the IFN-gamma-ELISPOT assay. If T cells were not expandable using native CLL cells as APC, leukemic cells were stimulated with CD40-ligand to increase the antigen-presenting capacity. This resulted in successful generation of MDM2-specific T cells in three of five remaining cases tested. Additionally, the factor that correlated best with successful generation of antigen-specific T cells in CLL patients was the ability of APCs to secrete IFN-gamma upon stimulation. CONCLUSION: In summary, MDM2(81-88) was shown for the first time in humans to elicit a functional autologous immune response. MDM2 was demonstrated to be naturally processed and presented as TAA in primary human CLL cells enabling expansion of functional autologous tumor-specific T cells.