Product Citations: 79

The emergence of SARS-CoV-2 variants has underscored the urgent need for innovative vaccine strategies that provide robust and enduring protection against diverse strains. Our study introduces the FP-HR5 nanoparticle vaccine, designed to target the highly conserved S2 subunit of the spike protein, including the fusion peptide (FP) and heptad repeats (HR1 and HR2), using a 24-mer Helicobacter pylori ferritin platform. Administered intranasally, the FP-HR5-NP vaccine elicits robust systemic and mucosal immune responses in vivo, generating high titers of FP- and HR5-specific IgG antibodies. Notably, intranasal immunization resulted in elevated levels of secretory IgA and IgG in bronchoalveolar lavage fluid (BALF) and stimulated T-cell immune responses, significantly increasing resident memory B cells (BRM) and resident memory T cells (TRM) in the lungs. In hACE2 transgenic mice, three doses of FP-HR5-NP conferred substantial protection against Delta and Omicron variant challenges, with undetectable viral RNA levels in the lungs and no pathological changes observed. Overall, the FP-HR5-NP vaccine triggers comprehensive humoral and cellular immune responses at the mucosa, providing broad defense against SARS-CoV-2 variants and positioning it as a promising candidate for a universal COVID-19 vaccine solution.
© 2025. The Author(s).

  • COVID-19
  • Immunology and Microbiology

Intranasal sarbecovirus vaccine booster elicits cross-clade, durable and protective systemic and mucosal immunity

Preprint on BioRxiv : the Preprint Server for Biology on 7 April 2025 by Cheang, N. Y. Z., Yap, W. C., et al.

ABSTRACT Short-lived, clade-specific immune responses with limited mucosal priming are limitations faced by current COVID-19 mRNA vaccines against sarbecoviruses. We have developed a nasal booster vaccine candidate that induced robust and sustained, cross-clade, systemic and mucosal protective immunity. Two recombinant Clec9A-specific monoclonal antibodies fused to the Receptor Binding Domain (RBD) from Omicron XBB.1.5 and SARS-CoV-1, respectively were generated. In Comirnaty mRNA-vaccinated mice, boosting with each individual Clec9A-RBD construct induced immune responses that either were limited in breadth or waned over time; while boosting with both constructs combined (Clec9A OMNI ) elicited robust cross-clade neutralizing antibodies (nAb) and T cell responses that were significantly more sustained compared to Bivalent Comirnaty (BC) mRNA vaccine booster. The persistence of RBD-specific follicular helper CD4 + T cells, germinal centre B cells, and long-lived plasma cells that facilitated affinity maturation in Clec9A OMNI -boosted mice, correlated with the detection of triple cross-reactive B cells that bind to ancestral SARS-CoV-2 ancestral, SARS-CoV-2 XBB.1.5 and SARS-CoV-1 RBD. Remarkably, intranasal boosting with Clec9A OMNI generated robust and sustained mucosal immune responses in the upper and lower respiratory compartments, including RBD-specific IgA, cross-clade nAb and cellular immunity together with functional tissue-resident memory T cells, without compromising the systemic immune responses. Correspondingly, Clec9A OMNI booster conferred superior protection against Omicron BA.1 compared to BC booster when challenge was performed at six months post-boost. Hence, Clec9A OMNI is a promising nasal booster vaccine candidate that has the potential to mitigate pandemic threats from emerging sarbecoviruses. One Sentence Summary Nasal booster immunization with dendritic cell-targeting vaccine candidate in mRNA-vaccinated mice induced cross-clade, sustained, systemic and mucosal protective immunity.

  • Immunology and Microbiology

Outbreaks of respiratory virus infections and arbovirus infections both pose a substantial threat to global public health. Clinically, both types of infection range from mild to severe and coinfections may occur more commonly than supposed. Our previous experimental coinfection study in mice demonstrated that prior infection with the arbovirus Semliki Forest virus (SFV) negatively impacted immune responses to influenza A virus (IAV). Here, we investigate whether simultaneous coinfection impacts the outcome of immune responses or disease. Simultaneous SFV and IAV infection did not lead to exacerbated or attenuated disease compared with the single virus infection control groups. SFV brain virus titers and brain pathology, including inflammation and immune responses, were comparable in the coinfection and single infection groups. By contrast, there was enhanced IAV replication, but no exacerbated lung pathology in coinfected mice. The magnitude of IAV-specific CD8+ T-cell responses in the lungs was lower compared with IAV-only infection. Considered along with our previous study, this study provides evidence that the timing of viral coinfection is pivotal in determining effects on immune responses, pathological changes and disease outcome.
© 2025 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.

  • Immunology and Microbiology

Dendritic-cell diversity in equine blood revealed by single-cell transcriptomics

Preprint on BioRxiv : the Preprint Server for Biology on 28 March 2025 by Botos, M., Baillou, A., et al.

ABSTRACT Unbiased classification of equine dendritic cells (DC) is necessary to address various research questions such as the role of DC subsets in immune-mediated diseases of horses. We applied single-cell RNA sequencing (scRNA-seq) on DC enriched from blood of two horses, based on expression of CD172a, Flt3, CADM1 and CD14. All main DC subsets were detected based on key gene expression, including cDC type 1 (cDC1; XCR1 ), cDC2 ( FCER1A , CD1E ) and plasmacytoid DC (pDC; TCF4 ). In addition, we detected a small cluster of CD34-expressing DC progenitors. Our data confirms the previously reported phenotype of equine pDC (MHC-II low CADM1 int CD172a int ), cDC1 (MHC-II high CADM1 high CD172a low-int ) and cDC2 (MHC-II high CADM1 int CD172a high ), while also highlighting considerable CD14 expression for cDC2. Among Flt3 + cells clustering with cDC2, we identified a cluster resembling monocytes and showing a highly pro-inflammatory signature, likely representing DC type 3 (DC3). Notably, one cDC2-associated cluster had a mixed pDC/cDC2 signature ( TCF4 , SPIB , FCER1A ), indicating the presence of transitional DC (tDC), a new DC subset initially described in human and mouse, and more recently in pig. To assess cross-species conservation of DC subsets, we compared equine and porcine DC scRNA-seq datasets using SATURN, a deep learning method that combines gene expression with added biological knowledge encoded in protein language models. This enabled mapping of the most similar DC subsets between horse and pig, confirming the conservation of key transcriptomic features and supporting the identification of equine tDC. Our atlas of equine blood DC is a valuable resource for comparative analyses, and it forms the foundation for elucidating the role of DC subsets in immunological diseases such as type I hypersensitivity in horses.

  • Cardiovascular biology
  • Immunology and Microbiology
  • Veterinary Research

The innate immune system plays a critical role in the rapid recognition and elimination of pathogens through pattern recognition receptors (PRRs). Among these PRRs are the C-type lectins (CTLs) langerin, mannan-binding lectin (MBL), and surfactant protein D (SP-D), which recognize carbohydrate patterns on pathogens. Each represents proteins from different compartments of the body and employs separate effector mechanisms. We have investigated their interaction with the Gram-positive opportunistic pathogen Staphylococcus aureus, a bacterium whose cell wall contains two key glycopolymers: capsular polysaccharide (CP) and wall teichoic acid (WTA). Using a langerin-expressing cell line and recombinant langerin, MBL, and SP-D, we demonstrated that langerin, MBL, and SP-D all recognize nonencapsulated S. aureus. However, the bacterium may produce CP that effectively shields S. aureus from recognition by all three CTLs. Experiments utilizing mutant S. aureus strains confirmed that WTA is a ligand for MBL, but that langerin likely interacts with an additional unknown ligand. A competition assay revealed that MBL and SP-D inhibit langerin's interaction with S. aureus, highlighting the intricate redundancy and cooperation within the innate immune system. This study highlights the dynamic interplay of langerin, MBL, and SP-D in recognizing specific surface structures on S. aureus and provides insight into how this pathogen evades innate immune recognition.
Copyright © 2025 Hymøller, Christiansen, Schlosser, Skov Sørensen, Lee and Thiel.

  • Immunology and Microbiology
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