An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

被引：92

作者：

Hassan, Ahmed O. ^{[1
]}

Shrihari, Swathi ^{[1
]}

Gorman, Matthew J. ^{[2
,3
]}

Ying, Baoling ^{[1
]}

Yaun, Dansu ^{[2
,3
]}

Raju, Saravanan ^{[1
,4
]}

Chen, Rita E. ^{[1
,4
]}

Dmitriev, Igor P. ^{[5
]}

Kashentseva, Elena ^{[5
]}

Adams, Lucas J. ^{[4
]}

Mann, Colin ^{[6
]}

Davis-Gardner, Meredith E. ^{[7
]}

Suthar, Mehul S. ^{[7
]}

Shi, Pei-Yong ^{[8
,9
,10
]}

Saphire, Erica Ollmann ^{[6
]}

Fremont, Daved H. ^{[4
,11
,12
]}

Curiel, David T. ^{[5
]}

Alter, Galit ^{[2
,3
]}

Diamond, Michael S. ^{[1
,4
,12
,13
]}

机构：

[1] Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA

[2] MIT, Ragon Inst, Massachusetts Gen Hosp MGH, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[3] Harvard Univ, Cambridge, MA USA

[4] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA

[5] Washington Univ, Dept Radiat Oncol, Sch Med, St Louis, MO 63110 USA

[6] La Jolla Inst Immunol, La Jolla, CA 92037 USA

[7] Emory Univ, Ctr Childhood Infect & Vaccines, Emory Vaccine Ctr, Dept Pediat,Childrens Healthcare Atlanta,Sch Med, Atlanta, GA 30322 USA

[8] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA

[9] Univ Texas Med Branch, Dept Microbiol, Sealy Inst Vaccine Sci, Galveston, TX 77555 USA

[10] Univ Texas Med Branch, Sealy Inst Vaccine Sci, Dept Immunol, Galveston, TX 77555 USA

[11] Washington Univ, Dept Biochem & Mol Biophys, Sch Med, St Louis, MO 63110 USA

[12] Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA

[13] Washington Univ Sch Med, Andrew M & Jane M Bursky Ctr Human Immunol & Immu, St Louis, MO 63110 USA

来源：

CELL REPORTS | 2021年 / 36卷 / 04期

关键词：

NEUTRALIZING ANTIBODIES; SINGLE INTRANASAL; ADENOVIRUS; MOUSE; ACE2;

D O I：

10.1016/j.celrep.2021.109452

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus- vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B. 1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARSCoV-2 strains.

引用

页数：17

共 68 条

[1] A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection [J].

Alsoussi, Wafaa B. ;

Turner, Jackson S. ;

Case, James B. ;

Zhao, Haiyan ;

Schmitz, Aaron J. ;

Zhou, Julian Q. ;

Chen, Rita E. ;

Lei, Tingting ;

Rizk, Amena A. ;

McIntire, Katherine M. ;

Winkler, Emma S. ;

Fox, Julie M. ;

Kafai, Natasha M. ;

Thackray, Larissa B. ;

Hassan, Ahmed O. ;

Amanat, Fatima ;

Krammer, Florian ;

Watson, Corey T. ;

Kleinstein, Steven H. ;

Fremont, Daved H. ;

Diamond, Michael S. ;

Ellebedy, Ali H. .

JOURNAL OF IMMUNOLOGY, 2020, 205 (04) :915-922

[2] Mechanisms that determine plasma cell lifespan and the duration of humoral immunity [J].

Amanna, Ian J. ;

Slifka, Mark K. .

IMMUNOLOGICAL REVIEWS, 2010, 236 :125-138

[3] Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine [J].

Baden, Lindsey R. ;

El Sahly, Hana M. ;

Essink, Brandon ;

Kotloff, Karen ;

Frey, Sharon ;

Novak, Rick ;

Diemert, David ;

Spector, Stephen A. ;

Rouphael, Nadine ;

Creech, C. Buddy ;

McGettigan, John ;

Khetan, Shishir ;

Segall, Nathan ;

Solis, Joel ;

Brosz, Adam ;

Fierro, Carlos ;

Schwartz, Howard ;

Neuzil, Kathleen ;

Corey, Larry ;

Gilbert, Peter ;

Janes, Holly ;

Follmann, Dean ;

Marovich, Mary ;

Mascola, John ;

Polakowski, Laura ;

Ledgerwood, Julie ;

Graham, Barney S. ;

Bennett, Hamilton ;

Pajon, Rolando ;

Knightly, Conor ;

Leav, Brett ;

Deng, Weiping ;

Zhou, Honghong ;

Han, Shu ;

Ivarsson, Melanie ;

Miller, Jacqueline ;

Zaks, Tal .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (05) :403-416

[4] SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies [J].

Barnes, Christopher O. ;

Jette, Claudia A. ;

Abernathy, Morgan E. ;

Dam, Kim-Marie A. ;

Esswein, Shannon R. ;

Gristick, Harry B. ;

Malyutin, Andrey G. ;

Sharaf, Naima G. ;

Huey-Tubman, Kathryn E. ;

Lee, Yu E. ;

Robbiani, Davide F. ;

Nussenzweig, Michel C. ;

West, Anthony P., Jr. ;

Bjorkman, Pamela J. .

NATURE, 2020, 588 (7839) :682-+

[5] Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses [J].

Barrett, Jordan R. ;

Belij-Rammerstorfer, Sandra ;

Dold, Christina ;

Ewer, Katie J. ;

Folegatti, Pedro M. ;

Gilbride, Ciaran ;

Halkerston, Rachel ;

Hill, Jennifer ;

Jenkin, Daniel ;

Stockdale, Lisa ;

Verheul, Marije K. ;

Aley, Parvinder K. ;

Angus, Brian ;

Bellamy, Duncan ;

Berrie, Eleanor ;

Bibi, Sagida ;

Bittaye, Mustapha ;

Carroll, Miles W. ;

Cavell, Breeze ;

Clutterbuck, Elizabeth A. ;

Edwards, Nick ;

Flaxman, Amy ;

Fuskova, Michelle ;

Gorringe, Andrew ;

Hallis, Bassam ;

Kerridge, Simon ;

Lawrie, Alison M. ;

Linder, Aline ;

Liu, Xinxue ;

Madhavan, Meera ;

Makinson, Rebecca ;

Mellors, Jack ;

Minassian, Angela ;

Moore, Maria ;

Mujadidi, Yama ;

Plested, Emma ;

Poulton, Ian ;

Ramasamy, Maheshi N. ;

Robinson, Hannah ;

Rollier, Christine S. ;

Song, Rinn ;

Snape, Matthew D. ;

Tarrant, Richard ;

Taylor, Stephen ;

Thomas, Kelly M. ;

Voysey, Merryn ;

Watson, Marion E. E. ;

Wright, Daniel ;

Douglas, Alexander D. ;

Green, Catherine M. .

NATURE MEDICINE, 2021, 27 (02) :279-+

[6] Discrete SARS-CoV-2 antibody titers track with functional humoral stability [J].

Bartsch, Yannic C. ;

Fischinger, Stephanie ;

Siddiqui, Sameed M. ;

Chen, Zhilin ;

Yu, Jingyou ;

Gebre, Makda ;

Atyeo, Caroline ;

Gorman, Matthew J. ;

Zhu, Alex Lee ;

Kang, Jaewon ;

Burke, John S. ;

Slein, Matthew ;

Gluck, Matthew J. ;

Beger, Samuel ;

Hu, Yiyuan ;

Rhee, Justin ;

Petersen, Eric ;

Mormann, Benjamin ;

Aubin, Michael de St ;

Hasdianda, Mohammad A. ;

Jambaulikar, Guruprasad ;

Boyer, Edward W. ;

Sabeti, Pardis C. ;

Barouch, Dan H. ;

Julg, Boris D. ;

Musk, Elon R. ;

Menon, Anil S. ;

Lauffenburger, Douglas A. ;

Nilles, Eric J. ;

Alter, Galit .

NATURE COMMUNICATIONS, 2021, 12 (01)

[7]

Bricker Traci L, 2020, bioRxiv, DOI [10.1016/j.celrep.2021.109400, 10.1101/2020.12.02.408823]

[8] Multiplexed Fc array for evaluation of antigen-specific antibody effector profiles [J].

Brown, Eric P. ;

Dowell, Karen G. ;

Boesch, Austin W. ;

Normandin, Erica ;

Mahan, Alison E. ;

Chu, Thach ;

Barouch, Dan H. ;

Bailey-Kellogg, Chris ;

Alter, Galit ;

Ackerman, Margaret E. .

JOURNAL OF IMMUNOLOGICAL METHODS, 2017, 443 :33-44

[9] Mouse and human FcR effector functions [J].

Bruhns, Pierre ;

Joensson, Friederike .

IMMUNOLOGICAL REVIEWS, 2015, 268 (01) :25-51

[10] Rational Vaccine Design in the Time of COVID-19 [J].

Burton, Dennis R. ;

Walker, Laura M. .

CELL HOST & MICROBE, 2020, 27 (05) :695-698

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