Vaccination as a Promising Approach in Cardiovascular Risk Mitigation: Are We Ready to Embrace a Vaccine Strategy? DOI Creative Commons

Georgios Tsioulos,

Natalia G. Vallianou, Alexandros Skourtis

и другие.

Biomolecules, Год журнала: 2024, Номер 14(12), С. 1637 - 1637

Опубликована: Дек. 20, 2024

Cardiovascular disease (CVD) remains a leading global health concern, with atherosclerosis being its principal cause. Standard CVD treatments primarily focus on mitigating cardiovascular (CV) risk factors through lifestyle changes and cholesterol-lowering therapies. As is marked by chronic arterial inflammation, the innate adaptive immune systems play vital roles in progression, either exacerbating or alleviating development. This intricate interplay positions system as compelling therapeutic target. Consequently, immunomodulatory strategies have gained increasing attention, though none yet reached widespread clinical adoption. Safety concerns, particularly suppression of host defenses, remain significant barrier to application anti-inflammatory Recent decades revealed role responses plaque-associated autoantigens atherogenesis, opening new perspectives for targeted immunological interventions. Preclinical models indicate that vaccines targeting specific atherosclerosis-related can slow progression while preserving systemic function. In this context, numerous experimental studies advanced understanding vaccine development exploring diverse pathways. Key include passive immunization using naturally occurring immunoglobulin G (IgG) antibodies active low-density lipoprotein cholesterol (LDL-C) apolipoproteins, such apolipoprotein B100 (ApoB100) CIII (ApoCIII). Other approaches involve formulations aimed at proteins regulate metabolism, including proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), angiopoietin-like 3 (ANGPTL3). Furthermore, literature highlights potential developing non-lipid-related vaccines, key targets heat shock (HSPs), interleukins (ILs), angiotensin III (Ang III), disintegrin metalloproteinase thrombospondin motifs 7 (ADAMTS-7). However, translating these promising findings into safe effective therapies presents substantial challenges. review provides critical evaluation current anti-atherosclerotic vaccination strategies, examines their proposed mechanisms action, discusses challenges need be overcome enable translation.

Язык: Английский

Deciphering the Human Germinal Center: A Review of Models to Study T–B Cell Interactions DOI Creative Commons

Elisa Fleischmann,

Vera Middelkamp,

Theo van den Broek

и другие.

European Journal of Immunology, Год журнала: 2025, Номер 55(2)

Опубликована: Фев. 1, 2025

Interactions between T- and B cells in the germinal center reaction are instrumental for initiation, maintenance, downregulation of human adaptive immune response, leading to production antigen-specific antibodies long-lasting immunological memory. Replicating system remains challenging, with an over-reliance on animal models limited translational accuracy. There is increasing need new tools that accurately model function. This review evaluates existing 2D 3D vitro ex vivo their ability reproduce reaction, a particular focus B-cell interaction. We conclude although current able replicate certain features no completely complex GC process. outline challenges recreating fully functional suggest future directions research improve models, ultimately bringing us closer reproducing lymph node.

Язык: Английский

Процитировано

1
Initiation of primary T cell—B cell interactions and extrafollicular antibody responses in an organized microphysiological model of the human lymph node DOI Creative Commons
Jonathan M. Zatorski, Desanka Raskovic, Abhinav Arneja

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

ABSTRACT Antibody production is central to protection against new pathogens and cancers, as well certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at extrafollicular border B cell follicles, where T lymphocytes physically interact drive maturation into antibody-secreting plasmablasts. In vitro models this process are sorely needed predict aspects human immune response. Microphysiological systems (MPSs) offer opportunity approximate lymphoid environment, but so far have focused primarily on memory recall responses antigens previously encountered by donor cells. To date, no 3D culture system has replicated engagement between cells (T—B interaction) that leads antibody when starting with naïve Here, we developed a LN-MPS model early T—B interactions built from primary, encapsulated within collagen-based matrix. Within MPS, exhibited CCL21-dependent chemotaxis chemokinesis predicted. Naïve were successfully skewed chip an follicular helper (pre-Tfh) activated state, respectively, co-culture latter led CD38+ plasmablast dependent IgM. These required differentiation pre-Tfhs, physical cell-cell contact, sensitive ratio which pre-Tfh seeded on-chip. Dependence was greatest 1:5 T:B ratio, while proliferation signal 1:1 ratio. Furthermore, formation established We envision MPS primary lymphocyte physiology will enable mechanistic analyses humoral immunity vitro.

Язык: Английский

Процитировано

0
Boosting B cells in blood-derived organoids DOI
Rebecca R. Pompano

Nature Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Язык: Английский

Процитировано

0
Boosting human immunology: harnessing the potential of immune organoids DOI Creative Commons
Maximilian Moll, Dirk Baumjohann

EMBO Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Язык: Английский

Процитировано

0
Functional organotypic human lymph node model with native immune cells benefits from fibroblastic reticular cell enrichment DOI Creative Commons
Andrew I. Morrison,

Jesse E Kuipers,

Henk P. Roest

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 10, 2025

Lymphoid organ function depends on fibroblastic reticular cells (FRCs), the non-hematopoietic mesenchymal stromal that crucially support immune activity in human lymph nodes (LNs). The vitro study of immunology requires physiological LN models, yet inclusion FRCs current models is lacking. Here, we created an organotypic hydrogel model, containing native from tissue and ex vivo cultured autologous FRCs. During a oneweek culture period, enrichment into model benefited viability all cell populations, particularly B cells, promoted presence certain subsets including CD4+ naïve T unswitched (US) memory cells. enhanced production immune-related cytokines chemokines, such as activating factor TNF family (BAFF), CXC motif chemokine ligand 12 (CXCL12), CC 19 (CCL19) interleukin-6 (IL-6). Functionality was assessed through activation by CD3 stimulation or initiation allogenic reaction with different maturation statuses monocyte-derived dendritic (moDCs). Interestingly, expansion restricted FRC-enriched reflecting intrinsic characteristic As such, this highlights influence allows opportunity to further antigen-induced responses, e.g. vaccine immunotherapy testing.

Язык: Английский

Процитировано

0
Vaccinology: Getting our modernization act together DOI
Ofer Levy

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(5)

Опубликована: Апрель 22, 2025

Ofer Levy, Director, Precision Vaccines Program at Boston Children’s Hospital, reflects on implications of the new FDA Modernization Act 2.0 accelerating drug and vaccine discovery development.

Язык: Английский

Процитировано

0
Ex vivorecapitulation of intramuscular mRNA vaccination with naïve and recall antigens using a human Lymphoid Follicle Chip platform DOI Creative Commons
Yunhao Zhai,

Min‐Wen Ku,

Ka Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Abstract Predicting the efficacy and toxicity of intramuscular mRNA vaccines remains challenging. Here, we describe an ex vivo human cell-based model that replicates immune responses to lipid nanoparticle (LNP)-based require injection. Vaccines are administered into a biomimetic muscle module containing skeletal myoblasts antigen-presenting cells (APCs) mimic vaccination, followed by transfer APCs soluble factors microfluidic lymphoid follicle chip (LF Chip) lymphatic drainage. Non-replicating directly induce antigen expression in APCs, whereas self-amplifying cell-APC contact within vaccination module. Transfer LF Chip induces expansion, de novo antigen-specific IgG production against naïve (rabies virus glycoprotein), cytokine release, with varying depending on LNP type. Vaccination chips SARS-COV-2 Spike recall using Moderna Spikevax vaccine generates neutralizing antibodies somatic hypermutation. This platform offers all-human alternative for evaluating vaccine-induced immunity, potentially obviating need non-human primates accelerating development.

Язык: Английский

Процитировано

0
Vaccination as a Promising Approach in Cardiovascular Risk Mitigation: Are We Ready to Embrace a Vaccine Strategy? DOI Creative Commons

Georgios Tsioulos,

Natalia G. Vallianou, Alexandros Skourtis

и другие.

Biomolecules, Год журнала: 2024, Номер 14(12), С. 1637 - 1637

Опубликована: Дек. 20, 2024

Cardiovascular disease (CVD) remains a leading global health concern, with atherosclerosis being its principal cause. Standard CVD treatments primarily focus on mitigating cardiovascular (CV) risk factors through lifestyle changes and cholesterol-lowering therapies. As is marked by chronic arterial inflammation, the innate adaptive immune systems play vital roles in progression, either exacerbating or alleviating development. This intricate interplay positions system as compelling therapeutic target. Consequently, immunomodulatory strategies have gained increasing attention, though none yet reached widespread clinical adoption. Safety concerns, particularly suppression of host defenses, remain significant barrier to application anti-inflammatory Recent decades revealed role responses plaque-associated autoantigens atherogenesis, opening new perspectives for targeted immunological interventions. Preclinical models indicate that vaccines targeting specific atherosclerosis-related can slow progression while preserving systemic function. In this context, numerous experimental studies advanced understanding vaccine development exploring diverse pathways. Key include passive immunization using naturally occurring immunoglobulin G (IgG) antibodies active low-density lipoprotein cholesterol (LDL-C) apolipoproteins, such apolipoprotein B100 (ApoB100) CIII (ApoCIII). Other approaches involve formulations aimed at proteins regulate metabolism, including proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), angiopoietin-like 3 (ANGPTL3). Furthermore, literature highlights potential developing non-lipid-related vaccines, key targets heat shock (HSPs), interleukins (ILs), angiotensin III (Ang III), disintegrin metalloproteinase thrombospondin motifs 7 (ADAMTS-7). However, translating these promising findings into safe effective therapies presents substantial challenges. review provides critical evaluation current anti-atherosclerotic vaccination strategies, examines their proposed mechanisms action, discusses challenges need be overcome enable translation.

Язык: Английский

Процитировано

1