Reprogramming human B cells with custom heavy-chain antibodies DOI Creative Commons
Paula M. Cannon, Geoffrey L. Rogers, Chun Huang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 17, 2023

We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells express custom molecules that respond immunization. These antibodies (HCAbs) comprise antigen-recognition domain linked an Fc derived from IgH and can be differentially spliced either cell receptor (BCR) or secreted antibody isoforms. The HCAb platform is highly flexible, supporting antigen-binding domains based on both non-antibody components, also allowing alterations in domain. Using HIV Env protein as model antigen, we show edited anti-Env HCAbs support regulated expression BCRs antibodies, antigen tonsil organoid In this way, reprogrammed produce customized therapeutic with potential for

Language: Английский

Understanding Mucosal Physiology and Rationale of Formulation Design for Improved Mucosal Immunity DOI

Mila Biswas,

Md Nurunnabi, Zehedina Khatun

et al.

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(8), P. 5037 - 5056

Published: May 24, 2024

The oral and nasal cavities serve as critical gateways for infectious pathogens, with microorganisms primarily gaining entry through these routes. Our first line of defense against invaders is the mucosal membrane, a protective barrier that shields body's internal systems from infection while also contributing to vital functions like air nutrient intake. One key features this its ability protect physiological system pathogens. Additionally, tolerance plays crucial role in maintaining homeostasis by regulating pH water balance within body. Recognizing importance barrier, researchers have developed various formulations enhance immune response. Mucosal vaccines, example, deliver antigens directly tissues, triggering local stimulation ultimately inducing systemic immunity. Studies shown lipid-based such liposomes virosomes can effectively elicit both responses. Furthermore, mucoadhesive polymeric particles, their prolonged delivery target sites, demonstrated an enhanced This Review delves into material selection approaches optimizing

Language: Английский

Citations

5
Regulation of pulmonary plasma cell responses during secondary infection with influenza virus DOI Creative Commons
Andrew J. MacLean, Joao P. P. Bonifacio, Sophia L. Oram

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(7)

Published: April 25, 2024

During secondary infection with influenza virus, plasma cells (PCs) develop within the lung, providing a local source of antibodies. However, site and mechanisms that regulate this process are poorly defined. Here, we show while circulating memory B entered lung during rechallenge were activated inducible bronchus-associated lymphoid tissues (iBALTs), resident (BRM) responded earlier, their activation occurred in different niche: directly near infected alveoli. This required NK but was largely independent CD4 CD8 T cells. Innate stimuli induced by virus-like particles containing ssRNA triggered BRM cell differentiation absence cognate antigen, suggesting low threshold activation. In contrast, expansion PCs iBALTs took longer to critically dependent on Our work demonstrates spatially distinct evolved support pulmonary PC responses, it reveals specialized function for as guardians

Language: Английский

Citations

4
Tissue-resident immune cells: from defining characteristics to roles in diseases DOI Creative Commons
Jia Li, Xiao Chu, Chunxiang Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 16, 2025

Tissue-resident immune cells (TRICs) are a highly heterogeneous and plastic subpopulation of that reside in lymphoid or peripheral tissues without recirculation. These endowed with notably distinct capabilities, setting them apart from their circulating leukocyte counterparts. Many studies demonstrate complex roles both health disease, involving the regulation homeostasis, protection, destruction. The advancement tissue-resolution technologies, such as single-cell sequencing spatiotemporal omics, provides deeper insights into cell morphology, characteristic markers, dynamic transcriptional profiles TRICs. Currently, reported TRIC population includes tissue-resident T cells, memory B (BRM) innate lymphocytes, macrophages, neutrophils (TRNs), mast but unignorably existence TRNs is controversial. Previous focus on one specific diseases, however, origins, developmental trajectories, intercellular cross-talks every type not fully summarized. In addition, systemic overview TRICs disease progression development parallel therapeutic strategies lacking. Here, we describe function characteristics all types major diseases. We shed light how to harness offer new targets present burning questions this field.

Language: Английский

Citations

0
B cells in non-lymphoid tissues DOI
Abrar Samiea,

George Celis,

Rashi Yadav

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

Citations

0
Signaling Activation and Modulation in Extrafollicular B Cell Responses DOI Creative Commons
Julian Staniek, Marta Rizzi

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: Feb. 7, 2025

ABSTRACT The differentiation of naive follicular B cells into either the germinal center (GC) or extrafollicular (EF) pathway plays a critical role in shaping type, affinity, and longevity effector cells. This choice also governs selection survival autoreactive cells, influencing their potential to enter memory compartment. During first 2–3 days following antigen encounter, initially activated integrate activating signals from T Toll‐like receptors (TLRs), cytokines, alongside inhibitory mediated by receptors. integration modulates intensity signaling, particularly PI3K/AKT/mTOR pathway, which central guiding developmental decisions. These early signaling events determine whether undergo GC maturation differentiate rapidly antibody‐secreting (ASCs) via EF pathway. Dysregulation these pathways—whether through excessive activation defective regulatory mechanisms—can disrupt balance between fates, predisposing individuals autoimmunity. Accordingly, aberrant has been implicated increasing risk autoimmune disease. review focuses on newly with an emphasis induction regulation It highlights gaps our understanding how alternative cell fates are regulated. Both physiological context implications inborn errors immunity (IEIs) complex conditions will be discussed this regard.

Language: Английский

Citations

0
A SARS-CoV-2 vaccine on an NIR-II/SWIR emitting nanoparticle platform DOI Creative Commons

Yongbo Jiang,

Mrinmoy Sanyal, Noor Hussein

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(6)

Published: Feb. 7, 2025

The COVID-19 pandemic caused a global health crisis that resulted in millions of deaths. Effective vaccines have played central roles curtailing the pandemic. Here, we developed down-converting near-infrared IIb (NIR-IIb; 1500 to 1700 nanometers) luminescent, pure NaErF4@NaYF4 rare-earth nanoparticle (pEr) as vaccine carriers. pEr nanoparticles were coated with three layers cross-linked biocompatible polymers (pEr-P3; ~55 and conjugated receptor binding domain (RBD) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Upon subcutaneous injection pEr-P3-RBD nanovaccine mice, vivo NIR-IIb imaging revealed active trafficking migration lymph nodes through lymphatic vessels. Two doses adjuvant-free elicited long-lasting (>7 months) high titers serum viral neutralization antibody anti-RBD immunoglobulin G, along robust RBD-specific germinal center B cells T follicular helper cells. We devised NIR-II molecular nodes, opening noninvasive assessments vaccine-elicited immune responses longitudinally.

Language: Английский

Citations

0
Ectopic germinal centers in the nasal turbinates contribute to B cell immunity to intranasal viral infection and vaccination DOI Creative Commons

Romain Gailleton,

Nimitha R. Mathew,

Laura Reusch

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(12)

Published: March 20, 2025

The nasal mucosa is the first immunologically active site that respiratory viruses encounter and establishing immunity at initial point of pathogen contact essential for preventing viral spread. Influenza A virus (IAV) in humans preferentially replicates upper tract (URT) but mouse models infection result lower infection. Here, we optimize IAV inoculation to enhance replication turbinate (NT) study local B cell immunity. We demonstrate URT-targeted stimulates robust responses, including germinal center (GC) formation NT, outside classical nasal-associated lymphoid tissues. NT GC contributes tissue-resident generation enhances antibody production. Furthermore, URT-focused immunization also induces significant NT. Finally, detect steady-state both mice healthy humans, suggesting continuous immune surveillance triggered by environmental stimuli. These findings highlight pivotal role systemic immunity, with important implications future mucosal vaccines targeting airways.

Language: Английский

Citations

0
Effective preparation and immunogenicity analysis of antigenic proteins for prevention of porcine enteropathogenic coronaviruses PEDV/TGEV/PDCoV DOI

Xinhao Jia,

Hang Liu,

Y P Sun

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142394 - 142394

Published: March 1, 2025

Language: Английский

Citations

0
Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses. DOI Open Access
Yixiang Deng,

Melbourne Tang,

Ted M. Ross

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 29, 2024

The on-going diversification of influenza virus necessicates annual vaccine updating. antigen, the viral spike protein hemagglutinin (HA), tends to elicit strain-specific neutralizing activity, predicting that sequential immunization with same HA strain will boost antibodies narrow coverage. However, repeated vaccination homologous SARS-CoV-2 eventually elicits activity against highly unmatched variants, questioning this immunological premise. We evaluated a longitudinal cohort, where each year subjects received same, novel H1N1 2009 pandemic strain. Repeated gradually enhanced receptor-blocking (HAI) strains within individuals no initial memory recall these historical viruses. An

Language: Английский

Citations

1
Reprogramming human B cells with custom heavy chain antibodies DOI Creative Commons
Geoffrey L. Rogers, Chun Huang,

Atishay Mathur

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 30, 2023

Abstract We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells express custom molecules that respond immunization. These antibodies (HCAbs) comprise antigen-recognition domain linked an Fc derived from IgH and can be differentially spliced either cell receptor (BCR) or secreted antibody isoforms. The HCAb platform is highly flexible, supporting antigen-binding domains based on both non-antibody components, also allowing alterations in domain. Using HIV Env protein as model antigen, we show edited anti-Env HCAbs support regulated expression BCRs antibodies, antigen tonsil organoid In this way, reprogrammed produce customized therapeutic with potential for vivo amplification.

Language: Английский

Citations

1