Brain cross-protection against SARS-CoV-2 variants by a lentiviral vaccine in new transgenic mice

被引：25

作者：

Ku, Min-Wen ^{[1
]}

Authie, Pierre ^{[1
]}

Bourgine, Maryline ^{[1
]}

Anna, Francois ^{[1
]}

Noirat, Amandine ^{[1
]}

Moncoq, Fanny ^{[1
]}

Vesin, Benjamin ^{[1
]}

Nevo, Fabien ^{[1
]}

Lopez, Jodie ^{[1
]}

Souque, Philippe ^{[1
]}

Blanc, Catherine ^{[1
]}

Fert, Ingrid ^{[1
]}

Chardenoux, Sebastien ^{[2
]}

Lafosse, Ilta ^{[2
]}

Cussigh, Delphine ^{[2
]}

Hardy, David ^{[3
]}

Nemirov, Kirill ^{[1
]}

Guinet, Francoise ^{[4
]}

Vives, Francina Langa ^{[2
]}

Majlessi, Laleh ^{[1
]}

Charneau, Pierre ^{[1
]}

机构：

[1] Inst Pasteur TheraVectys Joint Lab, Virol Dept, Paris, France

[2] Inst Pasteur, Plate Forme Ctr Ingn Genet Murine CIGM, Paris, France

[3] Inst Pasteur, Expt Neuropatholgy Unit, Paris, France

[4] Inst Pasteur, Immunol Dept, Lymphocytes & Immun Unit, Paris, France

来源：

EMBO MOLECULAR MEDICINE | 2021年 / 13卷 / 12期

基金：

欧盟地平线“2020”;

关键词：

central nervous system; hACE2 transgenic mice; intranasal vaccination; olfactory bulb; SARS-CoV-2 emerging variants of concern; SYNDROME CORONAVIRUS INFECTION; T-CELL RESPONSES; VECTORS; IMMUNIZATION; INTRANASAL; ORGAN;

D O I：

10.15252/emmm.202114459

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

COVID-19 vaccines already in use or in clinical development may have reduced efficacy against emerging SARS-CoV-2 variants. In addition, although the neurotropism of SARS-CoV-2 is well established, the vaccine strategies currently developed have not taken into account protection of the central nervous system. Here, we generated a transgenic mouse strain expressing the human angiotensin-converting enzyme 2, and displaying unprecedented brain permissiveness to SARS-CoV-2 replication, in addition to high permissiveness levels in the lung. Using this stringent transgenic model, we demonstrated that a non-integrative lentiviral vector, encoding for the spike glycoprotein of the ancestral SARS-CoV-2, used in intramuscular prime and intranasal boost elicits sterilizing protection of lung and brain against both the ancestral virus, and the Gamma (P.1) variant of concern, which carries multiple vaccine escape mutations. Beyond induction of strong neutralizing antibodies, the mechanism underlying this broad protection spectrum involves a robust protective T-cell immunity, unaffected by the recent mutations accumulated in the emerging SARS-CoV-2 variants.

引用

页数：21

共 50 条

[41] A novel DNA and protein combination COVID-19 vaccine formulation provides full protection against SARS-CoV-2 in rhesus macaques [J].

Li, Yuzhong ;

Bi, Yanwei ;

Xiao, Hongjian ;

Yao, Yueting ;

Liu, Xiaojuan ;

Hu, Zhengrong ;

Duan, Jinmei ;

Yang, Yaoyun ;

Li, Zhihua ;

Li, Yadong ;

Zhang, Heng ;

Ding, Chen ;

Yang, Jianbo ;

Li, Haiwei ;

He, Zhanlong ;

Liu, Longding ;

Hu, Guangnan ;

Liu, Shuying ;

Che, Yanchun ;

Wang, Shixia ;

Li, Qihan ;

Lu, Shan ;

Cun, Wei .

EMERGING MICROBES & INFECTIONS, 2021, 10 (01) :342-355

[42] 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

[43] Sublingual Dissolving Microneedle (SLDMN)-Based Vaccine for Inducing Mucosal Immunity against SARS-CoV-2 [J].

Kim, Youseong ;

Park, In Ho ;

Shin, Jiwoo ;

Choi, Jaibyung ;

Jeon, Chansol ;

Jeon, Seonghun ;

Shin, Jeon-Soo ;

Jung, Hyungil .

ADVANCED HEALTHCARE MATERIALS, 2023, 12 (26)

[44] Intranasal administration of a recombinant RBD vaccine induced protective immunity against SARS-CoV-2 in mouse [J].

Du, Yingying ;

Xu, Yuhua ;

Feng, Jin ;

Hu, Longbo ;

Zhang, Yanan ;

Zhang, Bo ;

Guo, Weili ;

Mai, Runming ;

Chen, Liyun ;

Fang, Jianmin ;

Zhang, Hui ;

Peng, Tao .

VACCINE, 2021, 39 (16) :2287-2294

[45] Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants [J].

Moser, Michael J. J. ;

Hill-Batorski, Lindsay ;

Bowen, Richard A. A. ;

Matejka, Sarah M. M. ;

Marshall, David ;

Kawaoka, Yoshihiro ;

Neumann, Gabriele ;

Bilsel, Pamuk .

VACCINES, 2023, 11 (06)

[46] A tetravalent Shigella outer membrane vesicles based candidate vaccine offered cross-protection against all the serogroups of Shigella in adult mice [J].

Bhaumik, Ushasi ;

Halder, Prolay ;

Howlader, Debaki Ranjan ;

Banerjee, Soumalya ;

Maiti, Suhrid ;

Dutta, Shanta ;

Koley, Hemanta .

MICROBES AND INFECTION, 2023, 25 (05)

[47] A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants [J].

Jiang, Linglei ;

Driedonks, Tom A. P. ;

Jong, Wouter S. P. ;

Dhakal, Santosh ;

van Saparoea, H. Bart van den Berg ;

Sitaras, Ioannis ;

Zhou, Ruifeng ;

Caputo, Christopher ;

Littlefield, Kirsten ;

Lowman, Maggie ;

Chen, Mengfei ;

Lima, Gabriela ;

Gololobova, Olesia ;

Smith, Barbara ;

Mahairaki, Vasiliki ;

Richardson, M. Riley ;

Mulka, Kathleen R. ;

Lane, Andrew P. ;

Klein, Sabra L. ;

Pekosz, Andrew ;

Brayton, Cory ;

Mankowski, Joseph L. ;

Luirink, Joen ;

Villano, Jason S. ;

Witwer, Kenneth W. .

JOURNAL OF EXTRACELLULAR VESICLES, 2022, 11 (03)

[48] Differential effects of SARS-CoV-2 variants on central nervous system cells and blood–brain barrier functions [J].

Alizé Proust ;

Christophe J. Queval ;

Ruth Harvey ;

Lorin Adams ;

Michael Bennett ;

Robert J. Wilkinson .

Journal of Neuroinflammation, 20

[49] Mandatory COVID-19 vaccination for healthcare personnel in the era of new SARS-CoV-2 variants [J].

Maltezou, Helena C. ;

Ledda, Caterina ;

Gagneux-Brunon, Amandine ;

Botelho-Nevers, Elisabeth .

VACCINE, 2022, 40 (50) :7167-7169

[50] Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2 [J].

Dicks, Matthew D. J. ;

Rose, Louisa M. ;

Russell, Rebecca A. ;

Bowman, Lesley A. H. ;

Graham, Carl ;

Jimenez-Guardeno, Jose M. ;

Doores, Katie J. ;

Malim, Michael H. ;

Draper, Simon J. ;

Howarth, Mark ;

Biswas, Sumi .

MOLECULAR THERAPY, 2022, 30 (12) :3639-3657

← 1 2 3 4 5 →