Biology subjects

Schön, K.

Publications and source records attributed to Schön, K..

4 recordsLinked to original sources

bioRxiv2025

Antibodies, Memory B Cells, and Antigen Valency Reshape B Cell Responses to Drifted Influenza Virus Vaccination

Antigenic drift in influenza A virus hemagglutinin (HA) limits humoral protective immunity. Here, we combine cell fate mapping with adoptive transfer of antigenic-site-specific antibodies (Abs) and memory B cells (MBCs) with moderately drifted HA vaccination in mice to better understand how this influences immune escape and protective responses. We demonstrate that drift in vaccine antigens affects MBC reactivation and naive B cell responses in germinal centers (GC). Strikingly, passively transferred monoclonal and polyclonal Abs suppress cognate epitope-specific GC B cell responses only when the vaccine antigen was multivalent while responses to monovalent recombinant trimeric HA remain unaffected. Using MBC and Abs co-transfer we unveil that antigenic site-specific suppression is more potent in blocking MBC rather than naive B cells entry into GC. In addition, we show that MBC hamper naive B cell recruitment to GC even in the absence of antibody transfer through local differentiation and Ab release in the responding lymph node. Altogether, our study reveals that serum Ab feedback depends on vaccine valency, while pre-existing MBC alone without Abs present can reshape immunodominance of naive B cells, with critical practical implications for rational universal influenza vaccine design.

immunology↗

bioRxiv2024

Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection

Influenza remains a persistent global health challenge, largely due to the virus continuous antigenic drift and shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanobodies, with their unique characteristics and binding capacity, offer a promising avenue to identify such epitopes. Here, we isolated and purified a hemagglutinin (HA)-specific nanobody that recognizes an H7 subtype of influenza A virus. Notably, the nanobody, named E10, exhibited broad-spectrum binding, cross-group neutralization and in vivo protection across various influenza A subtypes. Through phage display and in vitro characterization, we demonstrated that E10 specifically targets an epitope on HA head. This epitope is part of the conserved lateral patch of HA head and proved to be highly immunodominant upon H7 infection. Importantly, immunization with a peptide including the E10 epitope elicited cross-reactive antibodies and mediated partial protection from lethal viral challenge. Our data highlight the potential of E10 and its associated epitope as a candidate for future influenza prevention strategies.

microbiology↗

bioRxiv2024

Nasal tissue-resident memory CD4+ T cells persist after influenza A virus infection and provide heterosubtypic protection

CD4 tissue-resident memory T cells (TRM) are crucial adaptive immune components involved in preventing influenza A virus (IAV) infection. Despite their importance, their physiological role in the upper respiratory tract, the first site of contact with IAV, remains unclear. Here, we find that, after IAV infection, antigen-specific CD4 TRM persist in the nasal tissue (NT) compartment after infection and provide protection upon heterosubtypic challenge. Single cell RNA sequencing analysis reveals that NT CD4 TRM are heterogeneous and transcriptionally distinct as compared to their lung counterparts. Mechanistically, we demonstrate that the CXCR6-CXCL16 axis promotes CD4 TRM residency in the NT. Furthermore, we show that the NT of mice and humans contains a high frequency of Th17 CD4 TRM that aid in local viral clearance and in reducing tissue damage. Collectively, our results support a robust physiological role for nasal tissue CD4 TRM in local protection during heterosubtypic IAV infection.

immunology↗

bioRxiv2023

Tr1 cell-mediated protection against autoimmune disease by intranasal administration of a fusion protein targeting cDC1 cells

Curative therapies against autoimmune diseases are lacking. Indeed, most of currently available treatments are only targeting symptoms. We have developed a novel strategy for a therapeutic vaccine against autoimmune diseases based on intranasal administration of a fusion protein tolerogen, which consists of a mutant, enzymatically inactive, cholera toxin A1-subunit genetically fused to disease relevant high affinity peptides and a dimer of D-fragments from protein A. The CTA1R7K-MOG/PLP-DD fusion proteins effectively reduced clinical symptoms in the experimental autoimmune encephalitis (EAE)-model of multiple sclerosis (MS). The treatment induced Tr1 cells, in the draining lymph node, which produced IL-10 and suppressed effector CD4+ T cell responses. This effect was dependent on IL-27 signalling, since treatment was ineffective in bone marrow chimeras lacking IL-27R within their hematopoietic compartment. scRNA-seq of dendritic cells (DC) in draining lymph nodes demonstrated distinct gene transcriptional changes of cDC1, including enhanced lipid metabolic pathways, induced by the tolerogenic fusion protein. Thus, our results with the tolerogenic fusion protein demonstrates the possibility to vaccinate and protect against disease progression by reinstating tolerance in MS and other autoimmune diseases.

immunology↗