Recombinant OC43 SARS-CoV-2 spike replacement virus: An improved BSL-2 proxy virus for SARS-CoV-2 neutralization assays

被引：8

作者：

Hu, Zhe ^{[1
]}

Lopez-Munoz, Alberto Domingo ^{[1
]}

Kosik, Ivan ^{[1
]}

Li, Tiansheng ^{[1
]}

Callahan, Victoria ^{[2
]}

Brooks, Kelsie ^{[3
]}

Yee, Debra S. ^{[3
]}

Holly, Jaroslav ^{[1
]}

Santos, Jefferson J. S. ^{[1
]}

Brant, Ayslan Castro ^{[4
]}

Johnson, Reed F. ^{[5
]}

Takeda, Kazuyo ^{[1
,6
]}

Zheng, Zhi - Ming ^{[4
]}

Brenchley, Jason M. ^{[3
]}

Yewdell, Jonathan W. ^{[1
]}

Fox, Julie M. ^{[2
]}

机构：

[1] NIAID, Cellular Biol Sect, Lab Viral Dis, NIH, Bethesda, MD 20892 USA

[2] NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA

[3] NIAID, Barrier Immun Sect, Lab Viral Dis, NIH, Bethesda, MD 20892 USA

[4] NCI, Tumor Virus RNA Biol Sect, HIV Dynam & Replicat Program, NIH, Frederick, MD 21702 USA

[5] NIAID, SARS CoV 2 Virol Core, Lab Viral Dis, NIH, Bethesda, MD 20892 USA

[6] US FDA, Ctr Biol Evaluat & Res, Microscopy & Imaging Core Facil, Silver Spring, MD 20993 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2024年 / 121卷 / 29期

关键词：

coronavirus; mucosal vaccine; virus-- neutralizing antibodies; HCoV-OC43-OC43; CORONAVIRUS; VACCINE; INFECTION;

D O I：

10.1073/pnas.2310421121

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We generated a replication-- competent OC43 human seasonal coronavirus (CoV) expressing the severe acute respiratory syndrome coronavirus 2 (SARS-- CoV-2)- 2) spike in place of the native spike (rOC43-CoV2- CoV2 S). This virus is highly attenuated relative to OC43 and SARS-CoV-2- CoV- 2 in cultured cells and animals and is classified as a biosafety level 2 (BSL-2)- 2) agent by the NIH biosafety committee. Neutralization of rOC43-CoV2- CoV2 S and SARS-CoV-2- CoV- 2 by S-- specific monoclonal antibodies and human sera is highly correlated, unlike recombinant vesicular stomatitis virus-CoV2- CoV2 S. Single- dose immunization with rOC43-CoV2- CoV2 S generates high levels of neutralizing antibodies against SARS-CoV-2- CoV- 2 and fully protects human ACE2 transgenic mice from SARS-- CoV-2- 2 lethal challenge, despite nondetectable replication in respiratory and nonrespiratory organs. rOC43-CoV2- CoV2 S induces S-- specific serum and airway mucosal immunoglobulin A and IgG responses in rhesus macaques. rOC43-CoV2- CoV2 S has enormous value as a BSL-2- 2 agent to measure S-- specific antibodies in the context of a bona fide CoV and is a candidate live attenuated SARS-CoV-2- CoV- 2 mucosal vaccine that preferentially replicates in the upper airway.

引用

页数：11

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