Nucleoside modified mRNA vaccines for infectious diseases

Pardi, Norbert; Weissman, Drew

doi:10.1007/978-1-4939-6481-9_6

Cited by 129RNA Interference and Gene DeliveryImmunotherapy and Immune ResponsesSARS-CoV-2 and COVID-19 Research

Nucleoside modified mRNA vaccines for infectious diseases

Pardi, Norbert, Weissman, Drew·2017·Methods in molecular biology

DOI 10.1007/978-1-4939-6481-9_6

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Abstract

In recent years, numerous studies have demonstrated the outstanding abilities of mRNA to elicit potent immune responses against pathogens, making it a viable new platform for vaccine development (reviewed in Weissman, Expert Rev Vaccines 14:265-281, 2015; Sahin et al., Nat Rev Drug Discov 13:759-780, 2014). The incorporation of modified nucleosides in mRNA has many advantages and is currently undergoing a renaissance in the field of therapeutic protein delivery. Its use in a vaccine against infectious diseases has only begun to be described, but offers advantages for the generation of potent and long-lived antibody responses. FPLC purification and substitution of modified nucleosides in the mRNA make it non-inflammatory and highly translatable (Kariko et al., Immunity 23:165-175, 2005; Kariko et al., Mol Ther 16:1833-1840, 2008; Kariko et al., Nucleic Acids Research 39:e142, 2011) that are crucial features for therapeutic relevance. Formulation of the mRNA in lipid nanoparticles (LNPs) protects it from degradation enabling high levels of protein production for extended periods of time (Pardi et al., J Control Release, 2015). Here, we describe a simple vaccination method using LNP-encapsulated 1-methylpseudouridine-containing FPLC purified mRNA in mice. Furthermore, we describe the evaluation of antigen-specific T and B cell responses elicited by this vaccine format.

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Upscaling of cell-free vaccine production is relatively straightforward, providing a cutting-edge tool for rapid response in epidemics and pandemics.
“Furthermore, the upscaling of cell-free vaccine production is relatively straightforward, thereby providing a cutting-edge tool for rapid response in epidemics and pandemics.4, 5, 6, 7”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [7]

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Self-citation

Authors: Pardi, N., & Weissman, D.
Affiliations: University of Pennsylvania (US)
Corresponding author: Weissman, Drew
ORCID: Pardi, Norbert
Weissman, Drew
Venue: Methods in molecular biology
Publisher: Springer New York
Published: 2016-12-17
Volume: 1499
Pages: 109-121
ISSN: 1064-3745 (ISSN-L)
1940-6029
DOI: 10.1007/978-1-4939-6481-9_6
OpenAlex: W2565551608
Cited by: 129
References: 18
Citations by year: 2026: 5 · 2025: 13 · 2024: 17 · 2023: 16 · 2022: 22 · 2021: 18 · 2020: 16 · 2019: 5 · 2018: 10 · 2017: 7
FWCI: 9.04
Type: book chapter
Language: en
Open access: closed
Licence: www.springer.com/tdm (unspecified)
Locations: Methods in molecular biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords: mRNA vaccines, modified nucleosides, lipid nanoparticles, infectious disease vaccines, antibody response, T cell response, B cell response, immunogenicity
MeSH terms: Animals, Antibody Formation, B-Lymphocytes, Chromatography, High Pressure Liquid, Communicable Diseases, Lipids, Nucleosides, Pseudouridine, RNA, Messenger, T-Lymphocytes, Vaccination, Vaccines, Mice, Nanoparticles

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Nucleoside modified mRNA vaccines for infectious diseases

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