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增强的毒力和疫苗诱导抗体的减弱是由新冠病毒德尔塔毒株及其他毒株导致突破性感染的原因。

Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 delta and beyond.

作者信息

Kwon Hyung-Joon, Kosikova Martina, Tang Weichun, Ortega-Rodriguez Uriel, Radvak Peter, Xiang Ruoxuan, Mercer Kelly E, Muskhelishvili Levan, Davis Kelly, Ward Jerrold M, Kosik Ivan, Holly Jaroslav, Kang Insung, Yewdell Jonathan W, Plant Ewan P, Chen Wilbur H, Shriver Mallory C, Barnes Robin S, Pasetti Marcela F, Zhou Bin, Wentworth David E, Xie Hang

机构信息

Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.

Division of Biostatistics, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.

出版信息

iScience. 2022 Dec 22;25(12):105507. doi: 10.1016/j.isci.2022.105507. Epub 2022 Nov 5.

DOI:10.1016/j.isci.2022.105507
PMID:36373096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9635945/
Abstract

Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2 dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus and . By 5 months post-vaccination, ≥50% of donors lack detectable neutralizing antibodies against Delta and Kappa and all mice receiving 5-month post-vaccination sera die after the lethal challenges. Although a 3 vaccine dose can boost antibody neutralization against Delta and , the mean log neutralization titers against the latest Omicron subvariants are 1/3-1/2 of those against the original 614D virus. Our results suggest that enhanced virulence, greater immune evasion, and waning of vaccine-elicited protection account for SARS-CoV-2 variants caused breakthrough infections.

摘要

在此，我们在K18-hACE2转基因小鼠模型中探究了导致SARS-CoV-2突破性感染的因素。我们发现，Delta毒株及密切相关的Kappa变体可在K18-hACE2小鼠中引发病毒性肺炎和严重的肺部病变。接种2剂疫苗后的人类COVID-19 mRNA疫苗接种后血清在中和Delta/Kappa毒株方面的效率明显低于早期的614G病毒。接种疫苗5个月后，≥50%的供体缺乏可检测到的针对Delta和Kappa的中和抗体，且所有接受接种疫苗5个月后血清的小鼠在致死性攻击后死亡。尽管3剂疫苗可增强针对Delta毒株的抗体中和能力，但其针对最新奥密克戎亚变体的平均对数中和滴度仅为针对原始614D病毒的1/3至1/2。我们的结果表明，毒力增强、更强的免疫逃逸能力以及疫苗诱导的保护作用减弱是导致SARS-CoV-2变体引起突破性感染的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/6bae63d09c1f/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/c5bc2b5e6711/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/c2044a21c33a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/85a2c68b9567/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/f040fb3b9334/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/1ac03be7a8be/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/722cae399cd5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/d4d57ed2471b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/f25dd6867db3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/53cc6b7dd64d/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/3b7b1458a834/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/6bae63d09c1f/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/c5bc2b5e6711/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/c2044a21c33a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/85a2c68b9567/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/f040fb3b9334/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/1ac03be7a8be/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/722cae399cd5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/d4d57ed2471b/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/f25dd6867db3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/53cc6b7dd64d/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/3b7b1458a834/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6e6/9678741/6bae63d09c1f/gr10.jpg

相似文献

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引用本文的文献

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J Med Virol. 2025-7

[2]
Antibody-mediated SARS-CoV-2 entry in cultured cells.

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[3]
Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation.

Nat Commun. 2023-9-18

[4]
Current hotspot and study trend of innate immunity in COVID-19: a bibliometric analysis from 2020 to 2022.

Front Immunol. 2023

[5]
Identification of nurse shark V single-domain antibodies targeting the spike S2 subunit of SARS-CoV-2.

FASEB J. 2023-6

[6]
Heparan sulfate promotes ACE2 super-cluster assembly to enhance SARS-CoV-2-associated syncytium formation.

Res Sq. 2023-3-28

[7]
Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2.

J Med Virol. 2023-3

[8]
SKI-1/S1P Facilitates SARS-CoV-2 Spike Induced Cell-to-Cell Fusion via Activation of SREBP-2 and Metalloproteases, Whereas PCSK9 Enhances the Degradation of ACE2.

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本文引用的文献

[1]
Waning Effectiveness of the BNT162b2 Vaccine Against Infection in Adolescents in Israel.

Clin Infect Dis. 2023-1-6

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Lancet. 2022-7-23

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Nature. 2022-8

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MMWR Morb Mortal Wkly Rep. 2022-1-21

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Science. 2022-2-25

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SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters.

Nature. 2022-3

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