Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways

Li, Man; Zhao, Mengnan; Fu, Yao; Li, You; Gong, Tao; Zhang, Zhirong; Sun, Xun

doi:10.1016/j.jconrel.2016.02.043

Cited by 147 publications

(130 citation statements)

References 50 publications

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“…Cationic 1,2-dioleoyloxy-3-trimethylammoniumpropane (DOTAP) and dioleoylphosphatidylethanolamine (DOPE) lipid-complexed mRNA encoding HIV-1 gag generated antigen-specific CD4 + and CD8 + T cell responses after subcutaneous delivery in mice 109 . Two other studies demonstrated that PEI-complexed mRNAs could be efficiently delivered to mice to induce HIV-1-specific immune responses: subcutaneously delivered mRNA encoding HIV-1 gag elicited CD4 + and CD8 + T cell responses, and intranasally administered mRNA encoding the HIV-1 envelope gp120 subunit crossed the nasal epithelium and generated antigen-specific immune responses in the nasal cavity 110,111 . Kranz and colleagues also performed intravenous immunizations in mice using lipid-complexed mRNA encoding influenza virus HA and showed evidence of T cell activation after a single dose 59 .…”

Section: Mrna Vaccines Against Infectious Diseasesmentioning

confidence: 99%

mRNA vaccines — a new era in vaccinology

Pardi

Hogan

Porter

et al. 2018

Nat Rev Drug Discov

2,881

3,070

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mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.

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Section: Mrna Vaccines Against Infectious Diseasesmentioning

confidence: 99%

mRNA vaccines — a new era in vaccinology

Pardi

Hogan

Porter

et al. 2018

Nat Rev Drug Discov

2,881

3,070

View full text Add to dashboard Cite

show abstract

“…In one study, 2 kDa PEI conjugated to cyclodextrin was used as a safe carrier for mRNA encoding human immunodeficiency virus (HIV) gp120. Strong systemic and mucosal anti-HIV immune responses as well as production of cytokines were demonstrated [103]. In another study, 1.8 kDa PEI with its primary amines modified by different aromatic domains was evaluated.…”

Section: Nanotechnology Platforms For Mrna Deliverymentioning

confidence: 99%

“…One example is HIV-1 gag encoding mRNA complexed with DOTAP/DOPE, PEI or polyethyleneimine stearic acid copolymer in mice, which reportedly elicited antigen-specific CD4 + and CD8 + T cell responses [151, 152]. Cyclodextrin-PEI 2k conjugate-complexed mRNA encoding HIV-1 gp120 also led to strong mucosal and systemic immune responses [103]. LNP-formulated, modified mRNA encoding HA protein of H10N8 or H7N9 virus generated rapid and robust immune responses in mice, ferrets, non-human primates, and humans [153].…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Biomedical applications of mRNA nanomedicine

et al. 2018

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As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

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“…Polymers with highly dense polyamines surface, such as PEI, were shown to be highly efficient in delivering nucleic acid‐based vaccines, but were shown to have suboptimal toxicity profile to nasal epithelium. Linking anionic β‐cyclodextrin to PEI, lowers the charge density of the polyamine backbone, resulting in decreased cationic surface charge and increased nasal epithelium penetration of mRNA vaccine via intra‐ and paracellular pathways …”

Section: Rational Biomaterials Designmentioning

confidence: 99%

Immunology‐Guided Biomaterial Design for Mucosal Cancer Vaccines

et al. 2019

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Cancer of mucosal tissues is a major cause of worldwide mortality for which only palliative treatments are available for patients with late‐stage disease. Engineered cancer vaccines offer a promising approach for inducing antitumor immunity. The route of vaccination plays a major role in dictating the migratory pattern of lymphocytes, and thus vaccine efficacy in mucosal tissues. Parenteral immunization, specifically subcutaneous and intramuscular, is the most common vaccination route. However, this induces marginal mucosal protection in the absence of tissue‐specific imprinting signals. To circumvent this, the mucosal route can be utilized, however degradative mucosal barriers must be overcome. Hence, vaccine administration route and selection of materials able to surmount transport barriers are important considerations in mucosal cancer vaccine design. Here, an overview of mucosal immunity in the context of cancer and mucosal cancer clinical trials is provided. Key considerations are described regarding the design of biomaterial‐based vaccines that will afford antitumor immune protection at mucosal surfaces, despite limited knowledge surrounding mucosal vaccination, particularly aided by biomaterials and mechanistic immune–material interactions. Finally, an outlook is given of how future biomaterial‐based mucosal cancer vaccines will be shaped by new discoveries in mucosal vaccinology, tumor immunology, immuno‐therapeutic screens, and material–immune system interplay.

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Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways

Cited by 147 publications

References 50 publications

mRNA vaccines — a new era in vaccinology

mRNA vaccines — a new era in vaccinology

Biomedical applications of mRNA nanomedicine

Immunology‐Guided Biomaterial Design for Mucosal Cancer Vaccines

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