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Tejjani, K.

Publications and source records attributed to Tejjani, K..

3 recordsLinked to original sources

Adjuvant selection for optimally balanced humoral and cellular immunity induced by SARS-CoV-2 Spike virosome vaccines

Current SARS-CoV-2 vaccines provide limited breadth of protection, underscoring the need for vaccine strategies that optimize immune responses. Virosomesoffer a modular vaccine platform that enables multivalent antigen display and incorporation of adjuvants which can steer immune responses. We evaluated the immune response in BALB/c mice with virosomes displaying SARS-CoV-2 Wuhan or Delta spike antigens and coupled with various distinct adjuvants. Adjuvant selection differentially influenced both humoral and cellular immune outcomes. The TLR7/8 agonist 3M -052 induced a strong Th1-biased response, characterized by elevated IgG2a/IgG1 ratios and robust type 1 cytokine induction with suppression of Th2-associated cytokines. In contrast, the saponin QS-21 enhanced antibody functional quality, illustrated by improved virus neutralization potency and breadth. Furthermore, the combined incorporation of both 3M-052 and QS-21 induced an elevated Th1-biased response without improving neutralization capacity. In conclusion, different adjuvants added onto our virosome-basedvaccine led to distinct antibody responses and splenic T-cell profiles, reflective of differences in immune programming. This information guides the selection of adjuvants for respiratory virus vaccines.

immunology↗

Multimodal single-cell analysis following SARS-CoV-2 breakthrough infection reveals distinct B cell populations

B cells underpin durable immunity by generating long-lived memory B cells and antibody-secreting cells (ASCs) that re-engage upon antigen re-encounter. How human IgG memory B cells are organized to establish, maintain, and reactivate humoral immunity remains incompletely understood. Here, we combine multimodal single-cell profiling with longitudinal characterization of antigen-specific memory B cells following SARS-CoV-2 infection and vaccination to define the developmental relationships and biological functions of human IgG memory B cell subsets. We identify a coordinated activation-memory cycle shared by germinal center- and extrafollicular-derived memory B cells marked by differential CD45RB expression. Within this cycle, activated B cells represent specialized effector cells that acquire inflammatory responsiveness, migratory capacity, and differentiation potential toward ASCs. Activated memory B cells persist as an intermediate that retains migratory capacity while shifting toward homeostatic survival, preserving recall competence and contributing to the regeneration of long-lived resting memory. The resting memory compartment comprises two complementary populations: CD73 resting memory B cells form the principal long-lived recall reservoir, whereas CD24 resting memory B cells adopt a more regulatory resting state and shows limited participation in the SARS-CoV-2 recall response. We further identify a CD24 intermediate population as the earliest transitional state emerging upon memory B cell reactivation, bridging resting memory and the effector recall response. Together, these findings establish the human IgG memory B cell compartment as a dynamic activation-memory cycle rather than a collection of static subsets, providing a framework for understanding humoral immunity and interpreting B cell responses in vaccination, infection, and immune-mediated disease. One sentence summaryOur results provide novel insights on B cell recall responses after SARS-CoV-2 infection or vaccination, formulating distinct classical and non-classical re-activation trajectories from a resting memory state through intermediate phenotypes towards an activated state.

immunology↗

Large pan-cancer cell screen coupled to (phospho-) proteomics underscores high-dose vitamin C as a potent anti-cancer agent

Increasing preclinical and clinical evidence has positioned high-dose vitamin C as a promising anti-cancer treatment that merits more clinical attention. Multiple cytotoxicity mechanisms have been described, including pro-oxidant effects. To contribute to the preclinical understanding of the broad pan-cancer effects of high-dose vitamin C in a global manner, we determined the IC50 of a large panel of cancer cell lines (n=51) representing 7 solid tumour types and generated proteome data. The majority of cell lines were highly sensitive (IC50 range 0.036-10mM, mean 1.7 {+/-} 0.4 mM), well below a clinically achievable dose. The proteome data (>5000 proteins per sample), showed that high sensitivity is associated with proliferation, as indicated by functional enrichment of cell cycle, RNA splicing and chromatin organization, while lower sensitivity is linked to extracellular vesicles, glycolysis, fatty acid metabolism and mitochondria. Moreover, (phospho-)proteome analysis of on-treatment vitamin C effects on four pancreatic ductal adenocarcinoma (PDAC) cells dosed at a range of IC50 values (Hs766 T, 2 mM; Capan-2, 0.6 mM; PANC-1, 0.14 mM and Suit-2, 0.1 mM) revealed, next to cell line specific effects, down-modulation of AKT-MTOR signalling and immune suppressive signalling, while IFN- response was enhanced upon vitamin C. Altogether, our comprehensive pharmacological and (phospho-)proteome analysis is the first to assess cancer vulnerabilities and effects of vitamin C on a large cancer cell line panel and underscores the potential of high-dose vitamin C as an anti-cancer agent.

cancer biology↗