Design and development of mRNA and self-amplifying mRNA vaccine nanoformulations

Nanomedicine, Год журнала: 2024, Номер unknown, С. 1 - 27

Опубликована: Ноя. 13, 2024

The rapid evolution of mRNA vaccines, highlighted by Pfizer-BioNTech and Moderna's COVID-19 has transformed vaccine development therapeutic approaches. Self-amplifying (saRNA) a groundbreaking advancement in RNA-based offer promising possibilities for disease prevention treatment, including potential applications cancer neurodegenerative diseases. This review explores the complex design these innovative with focus on their nanoscale formulations that utilize nanotechnology to improve delivery effectiveness. It articulates fundamental principles saRNA mechanisms action, role synthetic eliciting immune responses. further elaborates various systems (e.g., lipid nanoparticles, polymeric nanoparticles other nanocarriers), emphasizing advantages enhancing stability cellular uptake. addresses advanced techniques such as microfluidics discusses challenges formulating vaccines. By incorporating latest technologies current research, this provides thorough overview recent nanovaccines advancements, highlighting revolutionize technology broaden clinical applications.

Язык: Английский

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Recent advances in mRNA-based cancer vaccines encoding immunostimulants and their delivery strategies

Journal of Controlled Release, Год журнала: 2024, Номер 376, С. 413 - 428

Опубликована: Окт. 24, 2024

Язык: Английский

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IL-7 promotes mRNA vaccine-induced long-term immunity

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 16, 2024

Messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, improving the immunogenicity durability of mRNA remains challenge. To elicit optimal immune responses, integrating antigen-encoded immunostimulatory adjuvants into single formulation is promising approach to enhancing efficacy vaccines. Here, we report an adjuvant strategy enhance by co-loading encoding antigen (rabies virus glycoprotein, RABV-G) IL-7 lipid nanoparticles, achieving co-delivery same antigen-presenting cells. A immunization with G&IL-7 vaccine elicited robust humoral responses mice conferred complete protection against RABV Notably, high levels neutralizing antibody induced were maintained for at least 6 months, providing long-term significant RABV. Additionally, also enhanced SARS-CoV-2. These data demonstrate that potent can provide required stimulation various formulations.

Язык: Английский

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Bispecific antibody targeting of lipid nanoparticles

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 22, 2024

Abstract Lipid nanoparticles (LNP) are the most clinically advanced non-viral gene delivery system. While progress has been made for enhancing delivery, cell specific targeting remains a challenge. Targeting moieties such as antibodies can be chemically-conjugated to LNPs however, this approach is complex and challenges scaling up. Here, we developed an generate antibody-conjugated that utilizes bispecific antibody (bsAb) bridge. As docking site bsAb, generated with short epitope, derived from hemagglutinin antigen (HA), embedded in PEG component of particle (LNP HA ). We bsAb which one domain binds other different surface proteins, including PD-L1, CD4, CD5, SunTag. Non-chemical conjugation LNP resulted major increase efficiency specificity transfecting cells expressing cognate target. LNP/bsAb mediated 4-fold vivo transfection PD-L1 cancer cells, 26-fold ex quiescent primary human T cells. Additionally, created universal recognizing anti-rat IgG2, enabling tethering off-the-shelf CD8, CD20, CD45, CD3. By utilizing molecular dock technology, these studies demonstrate simple effective strategy LNPs, precise efficient mRNA delivery.

Язык: Английский

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An Overview of Nanoparticle-Based Delivery Platforms for Vaccines

Опубликована: Май 13, 2024

With its unique properties and potential applications, nanoparticle-based delivery platforms for vac-cines have gained significant attention in recent years. Nanoparticles the advantages of enhancing immunogenicity, targeting improving stability, providing a new solution drug vaccine delivery. And some clinical studies, variety nanoparticle been gradually applied to wide range applications. Current research priorities are exploring various types nanoparticles as system enhance stability immunogen-icity. Lipid shown promising preclinical studies efficiently deliver antigens immune cells. Moreover, lipid (LNPs) other nu-cleic acids especially mRNA system, vast development. In this review, we present with an emphasis on nano-vaccine vehicles. We introduce several novel vac-cine such lipid, polymer, protein-based so on. addition, overview an-ti-tumor immunity nanovaccine against different tumors cancer immunotherapy. Finally, give outlook future perspectives remaining challenges technolo-gy-nanoparticle-based vaccines.

Язык: Английский

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Determining potential immunomodulatory drug efficacy in sepsis using ELISpot

Опубликована: Июль 16, 2024

ABSTRACT Purpose This study evaluated the ability of ELISpot to identify immuno-modulatory drug therapies for their potential efficacy in patients with sepsis. Methods was performed using diluted whole blood from 61 septic and 48 healthy matched controls. Innate adaptive immunity were by ex vivo stimulated production TNF-α IFN-γ respectively. Potential determined drugs’ effects increase or decrease number cytokine-producing cells amount cytokine produced per cell as spot size intensity. The corticosteroid dexamethasone its down modulate production. TLR7/8 agonist resiquimod (R848) T-cell stimulants IL-7 anti-PD-1 mAb tested enhance immune responses Results Spontaneous varied among subjects patients. LPS stimulation increased total 1,648% 1,929% Conversely, diminished 71% 61% IL-7, but not markedly both (127%) (79%). Dexamethasone also reduced anti-CD3/CD28 54%; while ameliorated dexamethasone-induced suppression. significantly enhanced lymphocyte function over 90% Conclusion can reveal host response patterns drugs selectively down– up-regulate patient immunity. Furthermore, detect effect specific independently regulate innate could enable precision-based

Язык: Английский

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MARCH8 Mediates K27-Linked Polyubiquitination of IL-7 Receptor α to Negatively Regulate IL-7–Triggered T Cell Homeostasis

The Journal of Immunology, Год журнала: 2024, Номер 213(10), С. 1467 - 1478

Опубликована: Сен. 23, 2024

Abstract IL-7 is a cytokine produced by stromal cells, which binds to IL-7Rα and plays an important role for homeostasis of T lymphocytes. Excessive activities IL-7–triggered signaling pathways causes autoimmune diseases. How immune effects are regulated not fully understood. In this study, we show that the membrane-associated RING-CH (MARCH) E3 ligase family member MARCH8 mediates K27-linked polyubiquitination IL-7Rα, leading its lysosomal degradation. Site-directed mutagenesis suggests meditates at K265/K266, mutation these residues renders resistance MARCH8-mediated deficiency increases activation downstream transcription factor STAT5 transcriptional induction effector genes in human lymphoma cells. also promotes cell proliferation splenic memory CD8+ differentiation mice. Our findings suggest negatively regulates mediating degradation reveals negative regulatory mechanism homeostasis.

Язык: Английский

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In vivo engineering chimeric antigen receptor immune cells with emerging nanotechnologies

Nano Today, Год журнала: 2024, Номер 59, С. 102517 - 102517

Опубликована: Окт. 10, 2024

Язык: Английский

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