A non-transmissible live attenuated SARS-CoV-2 vaccine

被引：10

作者：

Adler, Julia M. ^{[1
]}

Vidal, Ricardo Martin ^{[1
]}

Voss, Anne ^{[2
]}

Kunder, Sandra ^{[2
]}

Nascimento, Mariana ^{[1
]}

Abdelgawad, Azza ^{[1
]}

Langner, Christine ^{[1
]}

Vladimirova, Daria ^{[1
]}

Osterrieder, Nikolaus ^{[1
]}

Gruber, Achim D. ^{[2
]}

Kunec, Dusan ^{[1
]}

Trimpert, Jakob ^{[1
,3
]}

机构：

[1] Free Univ Berlin, Inst Virol, D-14163 Berlin, Germany

[2] Free Univ Berlin, Inst Tierpathol, D-14163 Berlin, Germany

[3] Free Univ Berlin, Inst Virol, Robert von Ostertag Str 7, D-14163 Berlin, Germany

来源：

MOLECULAR THERAPY | 2023年 / 31卷 / 08期

关键词：

COVID-19; live attenuated virus; mucosal vaccination; pneumonia; SARS-CoV-2; vaccine; virus transmission;

D O I：

10.1016/j.ymthe.2023.05.004

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Concep-tionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmis-sion of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV isa promising strategy to increase vac-cine safety and prevent vaccine transmission without compro-mising vaccine efficacy.

引用

页码：2391 / 2407

页数：17

共 48 条

[21] Synthetically recoded virus sCPD9 - A tool to accelerate SARS-CoV-2 research under biosafety level 2 conditions [J].

Kunec, Dusan ;

Osterrieder, Nikolaus ;

Trimpert, Jakob .

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, 2022, 20 :4376-4380

[22] Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction [J].

Lau, Siu-Ying ;

Wang, Pui ;

Mok, Bobo Wing-Yee ;

Zhang, Anna Jinxia ;

Chu, Hin ;

Lee, Andrew Chak-Yiu ;

Deng, Shaofeng ;

Chen, Pin ;

Chan, Kwok-Hung ;

Song, Wenjun ;

Chen, Zhiwei ;

To, Kelvin Kai-Wang ;

Chan, Jasper Fuk-Woo ;

Yuen, Kwok-Yung ;

Chen, Honglin .

EMERGING MICROBES & INFECTIONS, 2020, 9 (01) :837-842

[23] Designing transmissible viral vaccines for evolutionary robustness and maximum efficiency [J].

Layman, Nathan C. ;

Tuschhoff, Beth M. ;

Nuismer, Scott L. .

VIRUS EVOLUTION, 2021, 7 (01)

[24] Immunogenicity and safety of an inactivated whole-virus COVID-19 vaccine (VLA2001) compared with the adenoviral vector vaccine ChAdOx1-S in adults in the UK (COV-COMPARE): interim analysis of a randomised, controlled, phase 3, immunobridging trial [J].

Lazarus, Rajeka ;

Querton, Benedicte ;

Ramljak, Irena Corbic ;

Dewasthaly, Shailesh ;

Jaramillo, Juan Carlos ;

Dubischar, Katrin ;

Krammer, Michael ;

Weisova, Petronela ;

Hochreiter, Romana ;

Eder-Lingelbach, Susanne ;

Taucher, Christian ;

Finn, Adam .

LANCET INFECTIOUS DISEASES, 2022, 22 (12) :1716-1727

[25] Attenuated Vaccines Can Recombine to Form Virulent Field Viruses [J].

Lee, Sang-Won ;

Markham, Philip F. ;

Coppo, Mauricio J. C. ;

Legione, Alistair R. ;

Markham, John F. ;

Noormohammadi, Amir H. ;

Browning, Glenn F. ;

Ficorilli, Nino ;

Hartley, Carol A. ;

Devlin, Joanne M. .

SCIENCE, 2012, 337 (6091) :188-188

[26]

Li H, 2009, BIOINFORMATICS, V25, P1094, DOI [10.1093/bioinformatics/btp324, 10.1093/bioinformatics/btp100]

[27] Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 [J].

Liu, Zhe ;

Zheng, Huanying ;

Lin, Huifang ;

Li, Mingyue ;

Yuan, Runyu ;

Peng, Jinju ;

Xiong, Qianling ;

Sun, Jiufeng ;

Li, Baisheng ;

Wu, Jie ;

Yi, Lina ;

Peng, Xiaofang ;

Zhang, Huan ;

Zhang, Wei ;

Hulswit, Ruben J. G. ;

Loman, Nick ;

Rambaut, Andrew ;

Ke, Changwen ;

Bowden, Thomas A. ;

Pybus, Oliver G. ;

Lu, Jing .

JOURNAL OF VIROLOGY, 2020, 94 (17)

[28] Circulating vaccine-derived poliovirus: a menace to the end game of polio eradication [J].

Ming, Long Chiau ;

Hussain, Zahid ;

Yeoh, Siang Fei ;

Koh, David ;

Lee, Kah Seng .

GLOBALIZATION AND HEALTH, 2020, 16 (01)

[29] OPTIMAL ALIGNMENTS IN LINEAR-SPACE [J].

MYERS, EW ;

MILLER, W .

COMPUTER APPLICATIONS IN THE BIOSCIENCES, 1988, 4 (01) :11-17

[30] Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters [J].

Nouailles, Geraldine ;

Adler, Julia M. ;

Pennitz, Peter ;

Peidli, Stefan ;

Teixeira Alves, Luiz Gustavo ;

Baumgardt, Morris ;

Bushe, Judith ;

Voss, Anne ;

Langenhagen, Alina ;

Langner, Christine ;

Martin Vidal, Ricardo ;

Pott, Fabian ;

Kazmierski, Julia ;

Ebenig, Aileen ;

Lange, Mona V. ;

Muehlebach, Michael D. ;

Goekeri, Cengiz ;

Simmons, Szandor ;

Xing, Na ;

Abdelgawad, Azza ;

Herwig, Susanne ;

Cichon, Guenter ;

Niemeyer, Daniela ;

Drosten, Christian ;

Goffinet, Christine ;

Landthaler, Markus ;

Bluethgen, Nils ;

Wu, Haibo ;

Witzenrath, Martin ;

Gruber, Achim D. ;

Praktiknjo, Samantha D. ;

Osterrieder, Nikolaus ;

Wyler, Emanuel ;

Kunec, Dusan ;

Trimpert, Jakob .

NATURE MICROBIOLOGY, 2023, 8 (5) :860-874

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