Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines.
Johannes Lutz,Sandra Lazzaro,Mohamed Habbeddine,Kim Ellen Schmidt,Patrick Baumhof,Barbara L. Mui,Ying K. Tam,Thomas D. Madden,Michael J. Hope,Regina Heidenreich,Mariola Fotin-Mleczek +10 more
- Vol. 2, Iss: 1, pp 29-29
TLDR
This research shows that mRNA has promise as a versatile, cost-effective, rapidly scalable vaccine technology and demonstrates that mRNA can be developed to produce virus fragments that can prime a vaccinee’s immune system against a pathogen.Abstract:
mRNA represents a promising new vaccine technology platform with high flexibility in regard to development and production. Here, we demonstrate that vaccines based on sequence optimized, chemically unmodified mRNA formulated in optimized lipid nanoparticles (LNPs) are highly immunogenic and well tolerated in non-human primates (NHPs). Single intramuscular vaccination of NHPs with LNP-formulated mRNAs encoding rabies or influenza antigens induced protective antibody titers, which could be boosted and remained stable during an observation period of up to 1 year. First mechanistic insights into the mode of action of the LNP-formulated mRNA vaccines demonstrated a strong activation of the innate immune response at the injection site and in the draining lymph nodes (dLNs). Activation of the innate immune system was reflected by a transient induction of pro-inflammatory cytokines and chemokines and activation of the majority of immune cells in the dLNs. Notably, our data demonstrate that mRNA vaccines can compete with licensed vaccines based on inactivated virus or are even superior in respect of functional antibody and T cell responses. Importantly, we show that the developed LNP-formulated mRNA vaccines can be used as a vaccination platform allowing multiple, sequential vaccinations against different pathogens. These results provide strong evidence that the mRNA technology is a valid approach for the development of effective prophylactic vaccines to prevent infectious diseases.read more
Citations
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Journal ArticleDOI
Immunological considerations for COVID-19 vaccine strategies.
Mangalakumari Jeyanathan,Sam Afkhami,Fiona Smaill,Matthew S. Miller,Brian D. Lichty,Zhou Xing +5 more
TL;DR: The immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies are discussed and their strengths and potential shortfalls are examined, and inferences about their chances of success are made.
Journal ArticleDOI
Advances in mRNA Vaccines for Infectious Diseases.
TL;DR: Current research progress on mRNA vaccines is summarized, which have the potential to be quick-manufactured and to become powerful tools against infectious disease and the bright future of their design and applications are highlighted.
Journal ArticleDOI
New Vaccine Technologies to Combat Outbreak Situations.
TL;DR: Viral vector and nucleic acid-based vaccines (DNA and mRNA vaccines) are discussed as new approaches that might be able to tackle these challenges to global health.
Journal ArticleDOI
Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines
Kimberly J. Hassett,Kerry Benenato,Eric Jacquinet,Aisha Lee,Angela Woods,Olga Yuzhakov,Sunny Himansu,Jessica Deterling,Benjamin M. Geilich,Tatiana Ketova,Cosmin Mihai,Andy Lynn,Iain Mcfadyen,Melissa J. Moore,Joseph J. Senn,Matthew G. Stanton,Orn Almarsson,Giuseppe Ciaramella,Luis Brito +18 more
TL;DR: Screening a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model shows that mRNA vaccine tolerability can be improved without affecting potency.
Journal ArticleDOI
mRNA vaccines for infectious diseases: principles, delivery and clinical translation.
TL;DR: In 2019, the COVID-19 pandemic catalysed the most rapid vaccine development in history, with mRNA vaccines at the forefront of those efforts as mentioned in this paper, and although it is now clear that mRNA vaccines can rapidly and safely protect patients from infectious disease, additional research is required to optimize mRNA design, intracellular delivery and applications beyond SARS-CoV-2 prophylaxis.
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