The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
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 rema...
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| Vydané v: | iScience Ročník 24; číslo 12; s. 103479 |
|---|---|
| Hlavní autori: | , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
Elsevier Inc
17.12.2021
Elsevier |
| Predmet: | |
| ISSN: | 2589-0042, 2589-0042 |
| On-line prístup: | Získať plný text |
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| Abstract | 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.
[Display omitted]
•Lipid nanoparticles (LNPs) used for preclinical studies are highly inflammatory•The LNPs activate multiple inflammatory pathways and induce IL-1β and IL-6•The LNPs' inflammatory properties stem from their ionizable lipid component•The LNPs could be responsible for adjuvanticity and some of the side effects
Biological sciences; Immunology; Biotechnology |
|---|---|
| AbstractList | 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.
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Lipid nanoparticles (LNPs) used for preclinical studies are highly inflammatory
•
The LNPs activate multiple inflammatory pathways and induce IL-1β and IL-6
•
The LNPs' inflammatory properties stem from their ionizable lipid component
•
The LNPs could be responsible for adjuvanticity and some of the side effects
Biological sciences; Immunology; Biotechnology 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.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. 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. [Display omitted] •Lipid nanoparticles (LNPs) used for preclinical studies are highly inflammatory•The LNPs activate multiple inflammatory pathways and induce IL-1β and IL-6•The LNPs' inflammatory properties stem from their ionizable lipid component•The LNPs could be responsible for adjuvanticity and some of the side effects Biological sciences; Immunology; Biotechnology 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. |
| ArticleNumber | 103479 |
| Author | Ndeupen, Sonia Estanbouli, Henri Qin, Zhen Bouteau, Aurélie Igyártó, Botond Z. Jacobsen, Sonya |
| Author_xml | – sequence: 1 givenname: Sonia surname: Ndeupen fullname: Ndeupen, Sonia organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA – sequence: 2 givenname: Zhen surname: Qin fullname: Qin, Zhen organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA – sequence: 3 givenname: Sonya surname: Jacobsen fullname: Jacobsen, Sonya organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA – sequence: 4 givenname: Aurélie surname: Bouteau fullname: Bouteau, Aurélie organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA – sequence: 5 givenname: Henri surname: Estanbouli fullname: Estanbouli, Henri organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA – sequence: 6 givenname: Botond Z. surname: Igyártó fullname: Igyártó, Botond Z. email: botond.igyarto@jefferson.edu organization: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34841223$$D View this record in MEDLINE/PubMed |
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