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The emergence of SARS-CoV-2 variants escaping immunity challenges the efficacy of current vaccines. Here, we investigated humoral recall responses and vaccine-mediated protection in Syrian hamsters immunized with the third-generation Comirnaty® Omicron XBB.1.5-adapted COVID-19 mRNA vaccine, followed by infection with either antigenically closely (EG.5.1) or distantly related (JN.1) Omicron subvariants. Vaccination with the YF17D vector encoding a modified Gamma spike (YF-S0*) served as a control for SARS-CoV-2 immunity restricted to pre-Omicron variants. Our results show that both Comirnaty® XBB.1.5 and YF-S0* induce robust, however, poorly cross-reactive, neutralizing antibody (nAb) responses. In either case, total antibody and nAb levels increased following infection. Intriguingly, the specificity of these boosted nAbs did not match the respective challenge virus, but was skewed towards the primary antigen used for immunization, suggesting a marked impact of antigenic imprinting, confirmed by antigenic cartography. Furthermore, limited cross-reactivity and rapid decline in nAbs induced by Comirnaty® XBB.1.5 with EG.5.1 and, more concerning, JN.1, raises doubts about sustained vaccine efficacy against recent circulating Omicron subvariants. In conclusion, we demonstrate that antigenic imprinting plays a dominant role in shaping humoral immunity against emerging SARS-CoV-2 variants. Future vaccine design may have to address two major issues: (i) overcoming original antigenic sin that limits the breadth of a protective response towards emerging variants, and (ii) achieving sustained immunity that lasts for at least one season. [ABSTRACT FROM AUTHOR]

Summary: Live‐attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single‐dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS‐CoV‐2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D‐based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D‐based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Neuro-immune players of peripheral pain signalling," explores the interactions between the immune and nervous systems in the context of pain. It discusses the role of nociceptors, specialized sensory neurons that respond to harmful stimuli, and how their activation by inflammatory molecules can lead to chronic pain. The article includes two review articles and three original research articles that cover topics such as leukocyte infiltration in neuropathic pain, the effects of exercise on neuroimmune responses, and the mechanisms of pain sensitization. Overall, this research topic provides valuable insights into the complex relationship between the immune and nervous systems in pain signaling. [Extracted from the article]

p27kip1 is a multifunctional protein that promotes cell cycle exit by blocking the activity of cyclin/cyclin-dependent kinase complexes as well as migration and motility via signaling pathways that converge on the actin and microtubule cytoskeleton. Despite the broad characterization of p27kip1 function in neural cells, little is known about its relevance in microglia. Here, we studied the role of p27kip1 in microglia using a combination of in vitro and in situ approaches. While the loss of p27kip1 did not affect microglial density in the cerebral cortex, it altered their morphological complexity in situ. However, despite the presence of p27kip1 in microglial processes, as shown by immunofluorescence in cultured cells, loss of p27kip1 did not change microglial process motility and extension after applying laser-induced brain damage in cortical brain slices. Primary microglia lacking p27kip1 showed increased phagocytic uptake of synaptosomes, while a cell cycle dead variant negatively affected phagocytosis. These findings indicate that p27kip1 plays specific roles in microglia. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus colonization and release of enterotoxin B (SEB) has been associated with severe chronic rhinosinusitis with nasal polyps (CRSwNP). The pathogenic mechanism of SEB on epithelial barriers, however, is largely unexplored. Objective: We investigated the effect of SEB on nasal epithelial barrier function. Methods: SEB was apically administered to air‐liquid interface (ALI) cultures of primary polyp and nasal epithelial cells of CRSwNP patients and healthy controls, respectively. Epithelial cell integrity and tight junction expression were evaluated. The involvement of Toll‐like receptor 2 (TLR2) activation was studied in vitro with TLR2 monoclonal antibodies and in vivo in tlr2−/− knockout mice. Results: SEB applied to ALI cultures of polyp epithelial cells decreased epithelial cell integrity by diminishing occludin and zonula occludens (ZO)‐1 protein expression. Antagonizing TLR2 prevented SEB‐induced barrier disruption. SEB applied in the nose of control mice increased mucosal permeability and decreased mRNA expression of occludin and ZO‐1, whereas mucosal integrity and tight junction expression remained unaltered in tlr2−/− mice. Furthermore, in vitro SEB stimulation resulted in epithelial production of IL‐6 and IL‐8, which was prevented by TLR2 antagonization. Conclusion & Clinical relevance: SEB damages nasal polyp epithelial cell integrity by triggering TLR2 in CRSwNP. Our results suggest that SEB might represent a driving factor of disease exacerbation, rather than a causal factor for epithelial defects in CRSwNP. Interfering with TLR2 triggering might provide a way to avoid the pathophysiological consequences of S. aureus on inflammation in CRSwNP. [ABSTRACT FROM AUTHOR]