Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability DOI Creative Commons
Lizhou Zhang, Kunal R. More, Amrita Ojha

et al.

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 11, 2023

Abstract During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components distinct. Here, we compared effect of ionizable lipids, untranslated regions (UTRs), nucleotide composition two vaccines, focusing on delivery, antibody generation, long-term stability. We found that lipid, SM-102, Moderna’s vaccine performs better than ALC-0315 Pfizer-BioNTech’s for intramuscular delivery production mice stability at 4 °C. Moreover, 5′ UTR 3′ outperform their counterparts contribution to transgene expression mice. further varying N1-methylpseudouridine content wobble position has little efficacy. These findings may contribute improvement mRNA-LNP therapeutics.

Language: Английский

The role of lipid components in lipid nanoparticles for vaccines and gene therapy DOI

Camilla Hald Albertsen,

Jayesh A. Kulkarni, Dominik Witzigmann

et al.

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 188, P. 114416 - 114416

Published: July 3, 2022

Language: Английский

Citations

581
Circular RNA vaccines against SARS-CoV-2 and emerging variants DOI Creative Commons
Liang Qu, Zongyi Yi, Yong Shen

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(10), P. 1728 - 1744.e16

Published: April 1, 2022

As the emerging variants of SARS-CoV-2 continue to drive worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report circular RNA (circRNA) vaccine elicited potent neutralizing antibodies T cell responses by expressing trimeric RBD spike protein, providing robust protection against in both mice rhesus macaques. Notably, circRNA enabled higher durable antigen production than 1mΨ-modified mRNA proportion distinct Th1-skewed immune responses. Importantly, found circRNARBD-Omicron induced Omicron but not Delta variant. In contrast, circRNARBD-Delta protected or functioned as booster after two doses either native- Delta-specific vaccination, making it favorable choice current concern (VOCs) SARS-CoV-2.

Language: Английский

Citations

401
Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine DOI Open Access
Chunfeng Li, Audrey Lee, Lilit Grigoryan

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 543 - 555

Published: March 14, 2022

Language: Английский

Citations

335
The landscape of mRNA nanomedicine DOI Open Access
Xiangang Huang, Na Kong, Xingcai Zhang

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(11), P. 2273 - 2287

Published: Nov. 1, 2022

Language: Английский

Citations

310
Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery DOI Open Access
Xu Wang, Shuai Liu, Yehui Sun

et al.

Nature Protocols, Journal Year: 2022, Volume and Issue: 18(1), P. 265 - 291

Published: Oct. 31, 2022

Language: Английский

Citations

243
Correlates of protection against SARS‐CoV‐2 infection and COVID‐19 disease DOI
David Goldblatt, Galit Alter, Shane Crotty

et al.

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 6 - 26

Published: June 5, 2022

Antibodies against epitopes in S1 give the most accurate CoP infection by SARS-CoV-2 coronavirus. Measurement of those antibodies neutralization or binding assays both have predictive value, with antibody titers giving highest statistical correlation. However, protective functions are multiple. multiple other than influence efficacy. The role cellular responses can be discerned respect to CD4

Language: Английский

Citations

241
Innate immune mechanisms of mRNA vaccines DOI Creative Commons
R Verbeke, Michael J. Hogan, Karin Loré

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(11), P. 1993 - 2005

Published: Nov. 1, 2022

Language: Английский

Citations

230
Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies DOI Open Access
Barton F. Haynes, Kevin Wiehe, Persephone Borrow

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 142 - 158

Published: Aug. 12, 2022

Language: Английский

Citations

220
mRNA-based cancer therapeutics DOI
Chuang LIU,

Qiangqiang Shi,

Xiangang Huang

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(8), P. 526 - 543

Published: June 13, 2023

Language: Английский

Citations

219
Size-Dependent In Vivo Transport of Nanoparticles: Implications for Delivery, Targeting, and Clearance DOI
Mingze Xu,

Yuming Qi,

G.H. Liu

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(21), P. 20825 - 20849

Published: Nov. 3, 2023

Understanding the in vivo transport of nanoparticles provides guidelines for designing nanomedicines with higher efficacy and fewer side effects. Among many factors, size plays a key role controlling their behaviors due to existence various physiological thresholds within body size-dependent nano-bio interactions. Encouraged by evolving discoveries nanoparticle-size-dependent biological effects, we believe that it is necessary systematically summarize size-scaling laws nanoparticle vivo. In this review, summarized effect on along journey body: begin administration via different delivery routes, followed targeting intended tissues including tumors other organs, eventually clearance through liver or kidneys. We outlined tools investigating as well. Finally, discussed how may leverage tackle some challenges nanomedicine translation also raised important size-related questions remain be answered future.

Language: Английский

Citations

207