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COVID-19 Vaccine Development and Applications
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
The mRNA vaccine is a powerful technology to fight against a pandemic outbreak such as COVID-19. mRNA vaccines are a new form of vaccines that trigger immune responses by transfecting synthetic mRNA encoding viral antigens into human cells. These types of vaccines have several advantages such as rapid development, high yields from in vitro transcription reactions without risk of infection, and insertional mutagenesis. However, one major challenge for effective application of mRNA vaccines lies in the delivery at both the micro and macro levels. mRNA is rapidly degraded by extracellular RNases, and it cannot penetrate cell membranes to be transcribed in the cytosol. Therefore, intracellular delivery is essential to protect it from RNase degradation and facilitate cellular uptake of mRNA. To date, various delivery methods have been developed, including physical delivery methods, cationic peptide protamine, and cationic lipid nanoparticles (LNPs) delivery and ex vivo loading of dendritic cells. Among these, LNPs seem to be the most appealing and commonly used tool (38, 87). Most of the COVID-19 mRNA vaccines developed are based on LNP delivery because LNPs efficiently encapsulate and condense mRNA, promote intracellular delivery of mRNA to the cytosol by increasing cellular uptake and triggering endosomal escape, increase mRNA stability by protecting them from degradation in extracellular spaces, and are composed of biocompatible materials suitable for human use (38) (see Table 12.2).
Preparation, properties, applications and outlook of graphene-based materials in biomedical field: a comprehensive review
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Luyang Yao, Anqi Chen, Li Li, Yu Liu
GBMs have been reported as vaccine delivery vectors and immune adjuvants [147]. This material can be effectively internalized by dendritic cells and increase the capability of antigen presentation of immune cells. On the other hand, the immunogenicity of the material itself can enhance the immune system reactivity and promote the proliferation and differentiation of lymphocytes [80]. Yin et al. [141] reported an injectable hydrogel mRNA vaccine formed by GO and PEI, in which immune adjuvant (R848) and ovalbumin-encoded mRNA were encapsulated by π–π stacking and electrostatic interaction, significantly increased the number of antigen-specific CD8+ T cells. Xu et al. [142] developed a multi-functional nano-vaccine platform that used PEGylated rGO nanosheet as the vaccine carrier, rGO-PEG induces intracellular ROS in dendritic cells (DCs) to guide antigen processing and presentation to T cells, and a single injection of rGO-PEG vaccine induces an effective antigen-specific T cell response that last 30 days. A study evaluated the effects of GO nanosheets on synaptic formation in DC and DC-T cells and observed size-dependent interactions: GO with diameters >1 µm showed strong adhesion to the DC surface, while GO with diameters ≈500 nm was primarily internalized by DCs [148].
Lipid-based nanocarrier mediated CRISPR/Cas9 delivery for cancer therapy
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Aisha Aziz, Urushi Rehman, Afsana Sheikh, Mohammed A. S. Abourehab, Prashant Kesharwani
CRISPR/Cas9 cargo can be administrated in a variety of forms, one of which is an mRNA. An mRNA vaccine by the name of FixVac was developed as an RNA-LPX formulation against melanoma. After successful immunizations, more than 75% of patients developed immune responses against at least a single tumor related antigen. This shows the potential of LNPs based delivery of mRNA for its expression inside a cell and to exert a therapeutic action. This strategy can very well be applied to CRISPR/Cas9 mRNA delivery too [90].
Polymer-based nano-therapies to combat COVID-19 related respiratory injury: progress, prospects, and challenges
Published in Journal of Biomaterials Science, Polymer Edition, 2021
In the novel vaccine development for COVID-19, some studies have indicated that the viral S protein or receptor-binding domain (RBD) and N-terminal domain of S protein can be an excellent target for vaccine preparation in order to enhance the immunological response.[137] Different mRNA, DNA, and non-replicating adenovirus vector-based vaccines are under clinical trial to check their efficacy in COVID-19 treatment. The University of Oxford, in collaboration with AstraZeneca, developed a vaccine (AZD1222; formerly known as ChAdOX1) composed of a non-replicating adenovirus vector and able to replicate the S protein of SARS-CoV-2.[138] Some recently developed mRNA vaccine candidates are Moderna’s mRNA-1273 (NCT04405076), Arcturus Therapeutics’ LUNAR-COV19, BioNTech and Pfizer’s BNT162a1, b1, b2, and c2, Globe Biotech’s BANCOVID, and an CVnCoV developed by CureVac.[139–143] These mRNA vaccine candidates target the S protein (or a specific region of S protein) of the SARS-CoV-2 cell surface. On the other hand, vaccine candidates developed by Inovio Pharmaceuticals (INO-4800), Genexine’s GX-19, and Zydus Cadila’s ZyCoV-D are some DNA vaccines targeting viral S protein.[144,145] Epivax is a cocktail vaccine made up of antigens (i.e. non-structural proteins and nucleoproteins) other than S protein to provide partial protection against the virus.[146] Gamaleya Research institute developed Gam-COVID-Vac, and CanSino Biologics developed Ad5-nCoV to fight against SARS-CoV-2.[147] Johnson & Johnson also developed a vaccine candidate (Ad26.COV2.S), a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a stabilized full-length SARS-CoV-2 S protein.[148] Previously, this Ad26 vector was approved by the European Medicines Agency for the Respiratory syncytial virus, Zika virus, and Ebola virus.[148,149] Vaccine made of Ad26 vector is considered safe and highly immunogenic.[149] A couple of vaccine candidates developed by Sinopharm in collaboration with the Beijing Institute of Biological Products are currently in phase III clinical trial[146]. Some other protein-based vaccines, including COVAX-19 by Vaxine PTY Ltd. and NVX-CoV2373 by Novavax, are under clinical trials to evaluate their efficacy against COVID-19.[150] So far, vaccine candidates developed by Pfizer-BioNTech, Moderna, Oxford-AstraZeneca, Johnson & Johnson, CanSino, Sinopharm, Gamaleya, and Sinovac have been approved by health regulatory agencies throughout the world for early and emergency use.[151]