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Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines.

作者信息

Bae Ki Hyun, Shunmuganathan Bhuvaneshwari, Zhang Li, Lim Andrew, Gupta Rashi, Wang Yanming, Chua Boon Lin, Wang Yang, Gu Yue, Qian Xinlei, Tan Isabelle Siang Ling, Purushotorman Kiren, MacAry Paul A, White Kevin P, Yang Yi Yan

机构信息

Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, Centros #06-01, Singapore, 138668, Republic of Singapore.

Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Republic of Singapore.

出版信息

NPJ Vaccines. 2024 Feb 23;9(1):43. doi: 10.1038/s41541-024-00835-x.


DOI:10.1038/s41541-024-00835-x
PMID:38396073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10891077/
Abstract

The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses. The mRNA-LNP vaccines have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (<0.13), and high encapsulation efficiency (>90%). We employ in vivo bioluminescence imaging to illustrate the capacity of our LNPs to induce robust mRNA expression in secondary lymphoid organs. In a BALB/c mouse model, a three-dose subcutaneous immunization of mRNA-LNPs vaccines achieved remarkably high levels of cross-neutralization against the Omicron B1.1.529 and BA.2 variants for extended periods of time (28 weeks) with good safety profiles for all constructs when used in a booster regime, including the YN2016C bat virus sequences. These findings have important implications for the design of mRNA-LNP vaccines that aim to trigger durable cross-protective immunity against the current and newly emerging variants.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/dd14672dc1e5/41541_2024_835_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/ba7320ef0a99/41541_2024_835_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/ca585df5c568/41541_2024_835_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/a590fe161abb/41541_2024_835_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/dd14672dc1e5/41541_2024_835_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/ba7320ef0a99/41541_2024_835_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/ca585df5c568/41541_2024_835_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/a590fe161abb/41541_2024_835_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7893/10891077/dd14672dc1e5/41541_2024_835_Fig4_HTML.jpg

相似文献

[1]
Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines.

NPJ Vaccines. 2024-2-23

[2]
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Pharmaceutics. 2022-5-20

[3]
A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants.

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[4]
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[5]
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[6]
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Int J Mol Sci. 2022-7-12

[7]
Delivery and Expression of mRNA in the Secondary Lymphoid Organs Drive Immune Responses to Lipid Nanoparticle-mRNA Vaccines after Intramuscular Injection.

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[8]
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Mol Ther Methods Clin Dev. 2024-8-19

[9]
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Proc Natl Acad Sci U S A. 2023-12-26

[10]
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Microbiol Spectr. 2022-10-26

引用本文的文献

[1]
Muco-Penetrating Lipid Nanoparticles Having a Liquid Core for Enhanced Intranasal mRNA Delivery.

Adv Sci (Weinh). 2025-3

[2]
Expanding RNAi to Kidneys, Lungs, and Spleen via Selective ORgan Targeting (SORT) siRNA Lipid Nanoparticles.

Adv Mater. 2024-8

[3]
Design and Characterization of a New Formulation for the Delivery of COVID-19-mRNA Vaccine to the Nasal Mucosa.

Vaccines (Basel). 2024-4-12

本文引用的文献

[1]
A comprehensive survey of bat sarbecoviruses across China in relation to the origins of SARS-CoV and SARS-CoV-2.

Natl Sci Rev. 2022-10-11

[2]
An insight overview on COVID-19 mRNA vaccines: Advantageous, pharmacology, mechanism of action, and prospective considerations.

Int Immunopharmacol. 2023-4

[3]
Assessment of Immunogenicity and Efficacy of CV0501 mRNA-Based Omicron COVID-19 Vaccination in Small Animal Models.

Vaccines (Basel). 2023-1-31

[4]
Antibody Response to Omicron BA.4-BA.5 Bivalent Booster.

N Engl J Med. 2023-2-9

[5]
Bivalent Covid-19 Vaccines - A Cautionary Tale.

N Engl J Med. 2023-2-9

[6]
Nanoscopy for endosomal escape quantification.

Nanoscale Adv. 2020-10-27

[7]
Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2?

Biomed Pharmacother. 2022-10

[8]
Vaccine effectiveness against Delta, Omicron BA.1, and BA.2 in a highly vaccinated Asian setting: a test-negative design study.

Clin Microbiol Infect. 2023-1

[9]
SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns.

Cell Host Microbe. 2022-9-14

[10]
A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

J Biomed Sci. 2022-7-7

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