The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory

Summary: Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side eff...

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Autores principales:	Sonia Ndeupen, Zhen Qin, Sonya Jacobsen, Aurélie Bouteau, Henri Estanbouli, Botond Z. Igyártó
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Immunology Biotechnology Science Q
Acceso en línea:	https://doaj.org/article/8c4e06d68ede410195a0440cfbbaaac1
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spelling	oai:doaj.org-article:8c4e06d68ede410195a0440cfbbaaac12021-12-04T04:35:33ZThe mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory2589-004210.1016/j.isci.2021.103479https://doaj.org/article/8c4e06d68ede410195a0440cfbbaaac12021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221014504https://doaj.org/toc/2589-0042Summary: Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature.Sonia NdeupenZhen QinSonya JacobsenAurélie BouteauHenri EstanbouliBotond Z. IgyártóElsevierarticleBiological sciencesImmunologyBiotechnologyScienceQENiScience, Vol 24, Iss 12, Pp 103479- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Immunology Biotechnology Science Q
spellingShingle	Biological sciences Immunology Biotechnology Science Q Sonia Ndeupen Zhen Qin Sonya Jacobsen Aurélie Bouteau Henri Estanbouli Botond Z. Igyártó The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
description	Summary: Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature.
format	article
author	Sonia Ndeupen Zhen Qin Sonya Jacobsen Aurélie Bouteau Henri Estanbouli Botond Z. Igyártó
author_facet	Sonia Ndeupen Zhen Qin Sonya Jacobsen Aurélie Bouteau Henri Estanbouli Botond Z. Igyártó
author_sort	Sonia Ndeupen
title	The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
title_short	The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
title_full	The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
title_fullStr	The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
title_full_unstemmed	The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
title_sort	mrna-lnp platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/8c4e06d68ede410195a0440cfbbaaac1
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The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory

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