Human T follicular helper clones seed the germinal center–resident regulatory pool DOI Open Access
Carole Le Coz, Derek A. Oldridge, Ramin S. Herati

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(82)

Published: April 7, 2023

The mechanisms by which FOXP3+ T follicular regulatory (Tfr) cells simultaneously steer antibody formation toward microbe or vaccine recognition and away from self-reactivity remain incompletely understood. To explore underappreciated heterogeneity in human Tfr cell development, function, localization, we used paired TCRVA/TCRVB sequencing to distinguish tonsillar that are clonally related natural (nTfr) those likely induced helper (Tfh) (iTfr). proteins iTfr nTfr differentially expressed were pinpoint their situ locations via multiplex microscopy establish divergent functional roles. In silico analyses vitro tonsil organoid tracking models corroborated the existence of separate Treg-to-nTfr Tfh-to-iTfr developmental trajectories. Our results identify as a distinct CD38+, germinal center-resident, Tfh-descended subset gains suppressive function while retaining capacity help B cells, whereas CD38- elite suppressors primarily localized mantles. Interventions targeting specific subsets may provide therapeutic opportunities boost immunity more precisely treat autoimmune diseases.

Language: Английский

Emerging concepts in the science of vaccine adjuvants DOI Open Access
Bali Pulendran, Prabhu S. Arunachalam,

Derek T. O’Hagan

et al.

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(6), P. 454 - 475

Published: April 6, 2021

Language: Английский

Citations

991
Mucosal vaccines — fortifying the frontiers DOI Open Access
Ed C. Lavelle, Ross W. Ward

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(4), P. 236 - 250

Published: July 26, 2021

Language: Английский

Citations

518
Antibodies to combat viral infections: development strategies and progress DOI Creative Commons
Giuseppe Pantaleo, Bruno E. Correia, Craig Fenwick

et al.

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(9), P. 676 - 696

Published: June 20, 2022

Monoclonal antibodies (mAbs) are appealing as potential therapeutics and prophylactics for viral infections owing to characteristics such their high specificity ability enhance immune responses. Furthermore, antibody engineering can be used strengthen effector function prolong mAb half-life, advances in structural biology have enabled the selection optimization of potent neutralizing mAbs through identification vulnerable regions proteins, which also relevant vaccine design. The COVID-19 pandemic has stimulated extensive efforts develop against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several now having received authorization emergency use, providing not just an important component strategies combat but a boost harness therapeutic preventive settings other infectious diseases. Here, we describe discovery that led development use caused by viruses including SARS-CoV-2, syncytial virus (RSV), Ebola (EBOV), human cytomegalovirus (HCMV) influenza. We discuss rationale moving from empirical structure-guided development, based on identifying optimal candidate antigens within them targeted result strong protective response.

Language: Английский

Citations

158
The unique properties of IgG4 and its roles in health and disease DOI Open Access
Theo Rispens, Maartje G. Huijbers

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(11), P. 763 - 778

Published: April 24, 2023

Language: Английский

Citations

109
Characterization of nanoparticles-based vaccines for COVID-19 DOI Open Access
Giuditta Guerrini, Davide Magrì, Sabrina Gioria

et al.

Nature Nanotechnology, Journal Year: 2022, Volume and Issue: 17(6), P. 570 - 576

Published: June 1, 2022

Language: Английский

Citations

106
Human organoid models to study SARS-CoV-2 infection DOI Open Access
Yuling Han, Liuliu Yang, Lauretta A. Lacko

et al.

Nature Methods, Journal Year: 2022, Volume and Issue: 19(4), P. 418 - 428

Published: April 1, 2022

Language: Английский

Citations

100
Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ‐on‐a‐Chip DOI Creative Commons
Girija Goyal, Pranav Prabhala, Gautam Mahajan

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(14)

Published: March 14, 2022

Lymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model ectopic LF formation will provide a tool to understand development an alternative non-human primates preclinical evaluation vaccines. Here, it is shown that primary blood B- T-lymphocytes autonomously assemble into LFs when cultured 3D extracellular matrix gel within one channel two-channel organ-on-a-chip microfluidic device. Superfusion via parallel separated by microporous membrane required prevents lymphocyte autoactivation. These germinal center-like contain B cells expressing Activation-Induced Cytidine Deaminase exhibit plasma cell differentiation upon activation. To explore their utility seasonal vaccine testing, autologous monocyte-derived dendritic integrated Chips. The chips demonstrate improved antibody split virion influenza vaccination compared 2D cultures, which enhanced squalene-in-water emulsion adjuvant, this accompanied increases size number. When inoculated with commercial vaccine, production anti-hemagglutinin IgG observed, as well secretion cytokines similar vaccinated humans over clinically relevant timescales.

Language: Английский

Citations

81
A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2 DOI Creative Commons
Qian Yin, Wei Luo, Vamsee Mallajosyula

et al.

Nature Materials, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 30, 2023

Abstract The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable broad immune protection multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, leads persistent activation of cells responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant subdominant epitopes antigen-specific CD8 + T-cell in mice. This TLR7-NP-adjuvanted subunit successfully protects mice challenge different strain. strategy also the response variants that have emerged. Moreover, augments human tonsil organoids. Overall, improve promising implications developing broadly protective vaccines.

Language: Английский

Citations

63
Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment DOI
Roel Polak, Elisa Zhang, Calvin J. Kuo

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(8), P. 523 - 539

Published: July 8, 2024

Language: Английский

Citations

54
Blood Vessel Organoids for Development and Disease DOI
Kirill Salewskij, Josef Penninger

Circulation Research, Journal Year: 2023, Volume and Issue: 132(4), P. 498 - 510

Published: Feb. 16, 2023

Despite enormous advances, cardiovascular disorders are still a major threat to global health and responsible for one-third of deaths worldwide. Research new therapeutics the investigation their effects on vascular parameters is often limited by species-specific pathways lack high-throughput methods. The complex 3-dimensional environment blood vessels, intricate cellular crosstalks, organ-specific architectures further complicate quest faithful human in vitro model. development novel organoid models various tissues such as brain, gut, kidney signified leap field personalized medicine disease research. By utilizing either embryonic- or patient-derived stem cells, different developmental pathological mechanisms can be modeled investigated controlled environment. We have recently developed self-organizing capillary vessel organoids that recapitulate key processes vasculogenesis, angiogenesis, diabetic vasculopathy. Since then, this system has been utilized model other processes, refined, adapted organ specificity. In review, we will discuss alternative approaches engineering explore identity engineered vessels comparison vivo vasculature. Future perspectives therapeutic potential discussed.

Language: Английский

Citations

52