Search Results (5)

Background: Influenza viruses with truncated NS1 proteins show promise as viral vectors and candidates for mucosal universal influenza vaccines. These mutant NS1 viruses, which lack the N-terminal half of the NS1 protein (124 a.a.), are unable to antagonise the innate immune response. This creates a self-adjuvant effect enhancing heterologous protection by inducing a robust CD8+ T-cell response together with immunoregulatory mechanisms. However, the effects of NS1 modifications on T-follicular helper (Tfh) and B-cell responses remain less understood. Methods: C57bl/6 mice were immunised intranasally with 10 μL of either an influenza virus containing a truncated NS1 protein (PR8/NS124), a cold-adapted influenza virus with a full-length NS1 (caPR8/NSfull), or a wild-type virus (PR8/NSfull). Immune responses were assessed on days 8 and 28 post-immunisation by flow cytometry, ELISA, and HAI assay. Results: In this study, we demonstrate that intranasal immunisation with PR8/NS124 significantly increases tissue-resident CD4+ and CD8+ T cells in the lungs and activates Tfh cells in regional lymph nodes as early as day 8 post-immunisation. These effects are not observed in mice immunised with caPR8/NSfull or PR8/NSfull. Notably, PR8/NS124 immunisation also leads to the development of inducible bronchus-associated lymphoid tissue (iBALT) in the lungs by day 28, characterised by the presence of antigen-specific Tfh cells and GL7+Fas+ germinal centre B cells. Conclusions: Our findings further underscore the potential of NS1-truncated influenza viruses to drive robust mucosal immune responses and enhance vaccine efficacy. Full article

Background: Diesel exhaust particles (DEPs) are leading to a general increase in atopic diseases worldwide. However, it is still unknown whether DEPs induce systemic B-cell IgE class switching in secondary lymphoid organs or locally in the lungs in inducible bronchus-associated lymphoid tissue (iBALT). The aim of this work was to identify the exact site of DEP-mediated B-cell IgE class switching and pro-allergic antibody production. Methods: We immunized BALB/c mice with different OVA doses (0.3 and 30 µg) intranasally in the presence and absence of two types of DEPs, SRM1650B and SRM2786. We used low (30 µg) and high (150 µg) DEP doses. Results: Only a high DEP dose induced IgE production, regardless of the particle type. Local IgE class switching was stimulated upon treatment with both types of particles with both low and high OVA doses. Despite the similar ability of the two standard DEPs to stimulate IgE production, their ability to induce iBALT formation and growth was markedly different upon co-administration with low OVA doses. Conclusions: DEP-induced local IgE class switching takes place in preexisting iBALTs independent of de novo iBALT formation, at least in the case of SRM1650B co-administered with low OVA doses. Full article

Nucleotide-binding oligomerization domain 2 (NOD2) recognizes pathogens associated with the development of asthma. Moreover, NOD2 adjuvants are used in vaccine design to boost immune responses. Muramyl di-peptide (MDP) is a NOD2 ligand, which is able to promote Th2/Th17 responses. Furthermore, polymorphisms of the NOD2 receptor are associated with allergy and asthma development. This study aimed to evaluate if MDP given as an adjuvant during allergen sensitization may worsen the development of Th2/Th17 responses. We used a mouse model of Th2/Th17-type allergic neutrophil airway inflammation (AAI) to dog allergen, with in vitro polarization of human naive T cells by dendritic cells (DC) from healthy and dog-allergic asthma subjects. In the mouse model, intranasal co-administration of MDP did not modify the AAI parameters, including Th2/Th17-type lung inflammation. In humans, MDP co-stimulation of allergen-primed DC did not change the polarization profile of T cells in healthy subjects but elicited a Th2/Th17 profile in asthma subjects, as compared with MDP alone. These results support the idea that NOD2 may not be involved in the infection-related development of asthma and that, while care has to be taken in asthma patients, NOD2 adjuvants might be used in non-sensitized individuals. Full article

Mucosal surfaces are the first contact sites of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most SARS-CoV-2 vaccines induce specific IgG responses but provide limited mucosal immunity. Cytokine B-cell activation factor (BAFF) and A proliferation-inducing ligand (APRIL) in the tumor necrosis factor (TNF) superfamily play key immunological functions during B cell development and antibody production. Furthermore, homeostatic chemokines, such as C-X-C motif chemokine ligand 13 (CXCL13), chemokine (C–C motif) ligand 19 (CCL19), and CCL21, can induce B- and T-cell responses to infection and promote the formation of inducible bronchus-associated lymphoid tissues (iBALT), where specific local immune responses and memory cells are generated. We reviewed the role of BAFF, APRIL, CXCL13, CCL19, and CCL21 in the activation of local B-cell responses and antibody production, and the formation of iBALT in the lung following viral respiratory infections. We speculate that mucosal vaccines may offer more efficient protection against SARS-CoV-2 infection than systematic vaccines and hypothesize that a novel SARS-CoV-2 mRNA mucosal vaccine using BAFF/APRIL or CXCL13 as immunostimulants combined with the spike protein-encoding mRNA may enhance the efficiency of the local immune response and prevent the early stages of SARS-CoV-2 replication and the rapid viral clearance from the airways. Full article

Immunopathologic examination of the lungs of mouse models of experimental influenza virus infection provides new insights into the immune response in this disease. First, there is rapidly developing perivascular and peribronchial infiltration of the lung with T-cells. This is followed by invasion of T-cells into the bronchiolar epithelium, and separation of epithelial cells from each other and from the basement membrane leading to defoliation of the bronchial epithelium. The intraepithelial reaction may involve either CD8 or CD4 T-cytotoxic cells and is analogous to a viral exanthema of the skin, such as measles and smallpox, which occur when the immune response against these infections is activated and the infected cells are attacked by T-cytotoxic cells. Then there is formation of B-cell follicles adjacent to bronchi, i.e., induced bronchial associated lymphoid tissue (iBALT). iBALT reacts like the cortex of a lymph node and is a site for a local immune response not only to the original viral infection, but also related viral infections (heterologous immunity). Proliferation of Type II pneumocytes and/or terminal bronchial epithelial cells may extend into the adjacent lung leading to large zones filled with tumor-like epithelial cells. The effective killing of influenza virus infected epithelial cells by T-cytotoxic cells and induction of iBALT suggests that adding the induction of these components might greatly increase the efficacy of influenza vaccination. Full article