Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

被引：230

作者：

Tostanoski, Lisa H. ^{[1
]}

Wegmann, Frank ^{[2
]}

Martinot, Amanda J. ^{[1
,3
]}

Loos, Carolin ^{[4
,5
]}

McMahan, Katherine ^{[1
]}

Mercado, Noe B. ^{[1
]}

Yu, Jingyou ^{[1
]}

Chan, Chi N. ^{[6
]}

Bondoc, Stephen ^{[6
]}

Starke, Carly E. ^{[6
]}

Nekorchuk, Michael ^{[6
]}

Busman-Sahay, Kathleen ^{[6
]}

Piedra-Mora, Cesar ^{[1
,3
]}

Wrijil, Linda M. ^{[3
]}

Ducat, Sarah ^{[3
]}

Custers, Jerome ^{[2
]}

Atyeo, Caroline ^{[4
,7
]}

Fischinger, Stephanie ^{[4
,7
]}

Burke, John S. ^{[4
]}

Feldman, Jared ^{[4
,7
]}

Hauser, Blake M. ^{[4
,7
]}

Caradonna, Timothy M. ^{[4
,7
]}

Bondzie, Esther A. ^{[1
]}

Dagotto, Gabriel ^{[1
,7
]}

Gebre, Makda S. ^{[1
,7
]}

Jacob-Dolan, Catherine ^{[1
,7
]}

Lin, Zijin ^{[1
]}

Mahrokhian, Shant H. ^{[1
]}

Nampanya, Felix ^{[1
]}

Nityanandam, Ramya ^{[1
]}

Pessaint, Laurent ^{[8
]}

Porto, Maciel ^{[8
]}

Ali, Vaneesha ^{[8
]}

Benetiene, Dalia ^{[8
]}

Tevi, Komlan ^{[8
]}

Andersen, Hanne ^{[8
]}

Lewis, Mark G. ^{[8
]}

Schmidt, Aaron G. ^{[4
,7
,9
]}

Lauffenburger, Douglas A. ^{[5
]}

Alter, Galit ^{[4
,9
]}

Estes, Jacob D. ^{[6
]}

Schuitemaker, Hanneke ^{[2
]}

Zahn, Roland ^{[2
]}

Barouch, Dan H. ^{[1
,4
,7
,9
]}

机构：

[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA

[2] Janssen Vaccines & Prevent BV, Leiden, Netherlands

[3] Tufts Univ, Cummings Sch Vet Med, 200 Westboro Rd, North Grafton, MA 01536 USA

[4] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[5] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[6] Oregon Hlth & Sci Univ, Beaverton, OR USA

[7] Harvard Med Sch, Boston, MA 02115 USA

[8] Bioqual, Rockville, MD USA

[9] Massachusetts Consortium Pathogen Readiness, Boston, MA 02115 USA

来源：

NATURE MEDICINE | 2020年 / 26卷 / 11期

基金：

比尔及梅琳达.盖茨基金会; 美国国家卫生研究院;

关键词：

INFECTION; IMMUNITY; SARS;

D O I：

10.1038/s41591-020-1070-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death(1-4). Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters(5-7)and nonhuman primates(8-10)have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates(11-13). Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis. A single immunization with an adenovirus vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein induces protection against SARS-CoV-2-induced weight loss, pneumonia and mortality in hamsters.

引用

页码：1694 / +

页数：20

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