Poly(lactic acid) nanoparticles and cell-penetrating peptide potentiate mRNA-based vaccine expression in dendritic cells triggering their activation

Coolen, Anne-Line; Lacroix, Céline; Mercier-Gouy, Perrine; Delaune, Emilie; Monge, Claire; Exposito, Jean‐Yves; Verrier, Bernard

doi:10.1016/j.biomaterials.2018.12.019

Cited by 146 publications

(123 citation statements)

References 60 publications

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“…Phase I trial of mRNA-based rabies virus vaccine CV7201 demonstrated that it could be stored as a freeze-dried preparation at 5-25 • C for 3 years and at 40 • C for 6 months without obvious loss of activity [90]. In 2019, Coolen et al developed a poly(lactic acid)-nanoparticle-based mRNA vaccine, mixed with amphipathic cationic peptides, which showed stable expression efficacy after storage at 4 • C for up to 7 days [189]. Although further investigations are needed to study the effects of storage of mRNA complexed with vector molecules under unfrozen condition, studies has suggested the potential of mRNA vaccines for cold-chain free transport and storage in the future [169].…”

Section: Discussionmentioning

confidence: 99%

mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection

Yang

et al. 2020

IJMS

223

194

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Messenger ribonucleic acid (mRNA)-based drugs, notably mRNA vaccines, have been widely proven as a promising treatment strategy in immune therapeutics. The extraordinary advantages associated with mRNA vaccines, including their high efficacy, a relatively low severity of side effects, and low attainment costs, have enabled them to become prevalent in pre-clinical and clinical trials against various infectious diseases and cancers. Recent technological advancements have alleviated some issues that hinder mRNA vaccine development, such as low efficiency that exist in both gene translation and in vivo deliveries. mRNA immunogenicity can also be greatly adjusted as a result of upgraded technologies. In this review, we have summarized details regarding the optimization of mRNA vaccines, and the underlying biological mechanisms of this form of vaccines. Applications of mRNA vaccines in some infectious diseases and cancers are introduced. It also includes our prospections for mRNA vaccine applications in diseases caused by bacterial pathogens, such as tuberculosis. At the same time, some suggestions for future mRNA vaccine development about storage methods, safety concerns, and personalized vaccine synthesis can be found in the context.

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Section: Discussionmentioning

confidence: 99%

mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection

Yang

et al. 2020

IJMS

223

194

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“…Nanoparticle (NP)-based platforms offer a promising solution to not only effectively deliver mRNA but also other payloads such as adjuvants to improve therapeutic efficacy [ [39] , [40] , [41] , [42] , [43] ]. The design of such systems, however, is not without challenges.…”

Section: Introductionmentioning

confidence: 99%

Adjuvant-pulsed mRNA vaccine nanoparticle for immunoprophylactic and therapeutic tumor suppression in mice

et al. 2021

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Synthetic mRNA represents an exciting cancer vaccine technology to the implementation of effective cancer immunotherapy. However, inefficient in vivo mRNA delivery along with a requirement for immune co-stimulation present major hurdles to achieving anti-tumor therapeutic efficacy. Here, we demonstrate a proof-of-concept adjuvant-pulsed mRNA vaccine nanoparticle (NP) that is composed of an ovalbumin-coded mRNA and a palmitic acid-modified TLR7/8 agonist R848 (C16-R848), coated with a lipid-polyethylene glycol (lipid-PEG) shell. This mRNA vaccine NP formulation retained the adjuvant activity of encapsulated C16-R848 and markedly improved the transfection efficacy of the mRNA (>95%) and subsequent MHC class I presentation of OVA mRNA derived antigen in antigen-presenting cells. The C16-R848 adjuvant-pulsed mRNA vaccine NP approach induced an effective adaptive immune response by significantly improving the expansion of OVA-specific CD8 + T cells and infiltration of these cells into the tumor bed in vivo , relative to the mRNA vaccine NP without adjuvant. The approach led to an effective anti-tumor immunity against OVA expressing syngeneic allograft mouse models of lymphoma and prostate cancer, resulting in a significant prevention of tumor growth when the vaccine was given before tumor engraftment (84% reduction vs. control) and suppression of tumor growth when given post engraftment (60% reduction vs. control). Our findings indicate that C16-R848 adjuvant pulsation to mRNA vaccine NP is a rational design strategy to increase the effectiveness of synthetic mRNA vaccines for cancer immunotherapy.

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“…114,115 However, chemical and structural modifications to the mRNA and the addition of carrier molecules, including lipid nanoparticles (LNPs), protect the mRNA from degradation and facilitate cellular uptake. 116 This has been used successfully in Zika virus vaccine development, 117,118 and similar mRNA-LNP vaccine designs have elicited potent immune responses to influenza virus in animal and human studies. 119 One preclinical study found that immunization of humanized mice with low doses of mRNA-LNPs encoding VRC01 bNAbs yielded high levels of protective antibodies against HIV-1 infection.…”

Section: Rna-based Vaccinesmentioning

confidence: 99%

Innovations in HIV-1 Vaccine Design

Jones

Moody

Thompson

2020

Clinical Therapeutics

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Purpose: The field of HIV-1 vaccinology has evolved during the last 30 years from the first viral vector HIV gene insert constructs to vaccination regimens using a myriad of strategies. These strategies now include germline-targeting, lineagebased, and structure-guided immunogen design. This narrative review outlines the historical context of HIV vaccinology and subsequently highlights the scientific discoveries during the last 6 years that promise to propel the field forward.Methods: We conducted a search of 2 electronic databases, PubMed and EMBASE, for experimental studies that involved new HIV immunogen designs between 2013 and 2019. During the title and abstract reviews, publications were excluded if they were written in language other than English and/or were a letter to the editor, a commentary, or a conference-only presentation. We then used ClinicalTrials.gov to identify completed and ongoing clinical trials using these strategies.Findings: The HIV vaccinology field has undergone periods of significant growth during the last 3 decades. Findings elucidated in preclinical studies have revealed the importance of the interaction between the cellular and humoral immune system. As a result, several new rationally designed vaccine strategies have been developed and explored in the last 6 years, including native-like envelope trimers, nanoparticle, and mRNA vaccine design strategies among others. Several of these strategies have shown enough promise in animal models to progress toward first-inhuman Phase I clinical trials.Implications: Rapid developments in preclinical and early-phase clinical studies suggest that a tolerable and effective HIV vaccine may be on the horizon. (Clin Ther. xxxx;xxx:xxx)

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Poly(lactic acid) nanoparticles and cell-penetrating peptide potentiate mRNA-based vaccine expression in dendritic cells triggering their activation

Cited by 146 publications

References 60 publications

mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection

mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection

Adjuvant-pulsed mRNA vaccine nanoparticle for immunoprophylactic and therapeutic tumor suppression in mice

Innovations in HIV-1 Vaccine Design

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