Adenovirus-based vaccines—a platform for pandemic preparedness against emerging viral pathogens

Molecular Therapy, Год журнала: 2022, Номер 30(5), С. 1822 - 1849

Опубликована: Янв. 31, 2022

Zoonotic viruses continually pose a pandemic threat. Infection of humans with for which we typically have little or no prior immunity can result in epidemics high morbidity and mortality. These public health economic impact exacerbate civil unrest political instability. Changes human behavior the past few decades-increased global travel, farming intensification, exotic animal trade, warming on migratory patterns, habitats, ecosystems-contribute to increased frequency cross-species transmission events. Investing pre-clinical advancement vaccine candidates against diverse emerging viral threats is crucial preparedness. Replication-defective adenoviral (Ad) vectors demonstrated their utility as an outbreak-responsive platform during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Ad are easy engineer; amenable rapid, inexpensive manufacturing; relatively safe immunogenic humans; and, importantly, do not require specialized cold-chain storage, making them ideal equitable distribution stockpiling. In this review, discuss progress applying Ad-based vaccines summarize safety profile, reflected by widespread geographic use SARS-CoV-2

Язык: Английский

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Biomimetic Exosomes: A New Generation of Drug Delivery System

Frontiers in Bioengineering and Biotechnology, Год журнала: 2022, Номер 10

Опубликована: Май 23, 2022

Most of the naked drugs, including small molecules, inorganic agents, and biomacromolecule cannot be used directly for disease treatment because their poor stability undesirable pharmacokinetic behavior. Their shortcomings might seriously affect exertion therapeutic effects. Recently, a variety exogenous endogenous nanomaterials have been developed as carriers drug delivery. Among them, exosomes attracted great attention due to excellent biocompatibility, low immunogenicity, toxicity, ability overcome biological barriers. However, delivery significant challenges, such yields, complex contents, homogeneity, which limit application. Engineered or biomimetic fabricated through approaches tackle these drawbacks. We summarized recent advances in over past decades addressed opportunities challenges next-generation system.

Язык: Английский

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Advances in the polymeric delivery of nucleic acid vaccines

Theranostics, Год журнала: 2022, Номер 12(9), С. 4081 - 4109

Опубликована: Янв. 1, 2022

Nucleic acid vaccines, especially messenger RNA (mRNA) display unique benefits in the current COVID-19 pandemic.The application of polymeric materials as delivery carriers has greatly promoted nucleic vaccine a promising prophylactic and therapeutic strategy.The inherent properties render vaccines with excellent vivo stability, enhanced biosafety, specific cellular uptake, endolysosomal escape, antigen expression.Although progressed significantly past decades, clinical translation polymer-gene systems still faces insurmountable challenges.This review summarizes diverse polymers their characterizations representative formulations for delivery.We also discussed existing problems, coping strategies, prospect relevant to applications carriers.This highlights rational design development towards meeting goals defending serious or emerging diseases.

Язык: Английский

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Arginine Supplementation Targeting Tumor-Killing Immune Cells Reconstructs the Tumor Microenvironment and Enhances the Antitumor Immune Response

ACS Nano, Год журнала: 2022, Номер 16(8), С. 12964 - 12978

Опубликована: Авг. 15, 2022

The tumor microenvironment (TME) is characterized by several immunosuppressive factors, of which weak acidity and l-arginine (l-arg) deficiency are two common features. A acidic environment threatens the survival immune cells, insufficient l-arg will severely restrain effect antitumor responses, both affect efficiency cancer treatments (especially immunotherapy). Meanwhile, essential for progression. Thus, strategies, supplementation deprivation, developed treatment. However, these strategies have potential risk promoting growth impairing might lead to a paradoxical therapeutic effect. It optimal limit availability cells from while supplying cells. In this study, we designed multivesicular liposome technology continuously supply alkaline l-arg, simultaneously changed in TME, selectively knocking down CAT-2 transporter, starvation tumors was maintained tumor-killing were enriched TME. results showed that our strategy promoted infiltration activation CD8+ T tumor, increased proportion M1 macrophages, inhibited melanoma growth, prolonged survival. combination with anti-PD-1 antibody, reversed low response checkpoint blockade therapy, showing synergistic Our work provided reference improving TME combined regulating nutritional competitiveness achieve sensitization immunotherapy.

Язык: Английский

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Advances of mRNA vaccine in tumor: a maze of opportunities and challenges

Biomarker Research, Год журнала: 2023, Номер 11(1)

Опубликована: Янв. 18, 2023

Abstract High-frequency mutations in tumor genomes could be exploited as an asset for developing vaccines. In recent years, with the tremendous breakthrough genomics, intelligence algorithm, and in-depth insight of immunology, it has become possible to rapidly target genomic alterations cell rationally select vaccine targets. Among a variety candidate platforms, early application mRNA was limited by instability low efficiency excessive immunogenicity until successful development vaccines against SARS-COV-2 broken technical bottleneck preparation, allowing prepared economical way good performance stability efficiency. this review, we systematically summarized classification characteristics antigens, general process methods screening neoantigens, strategies preparations advances clinical trials, well presented main challenges current development.

Язык: Английский

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