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

被引:225
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
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
收藏
页码:1694 / +
页数:20
相关论文
共 25 条
  • [1] Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D
    Abbink, Peter
    Lemckert, Angelique A. C.
    Ewald, Bonnie A.
    Lynch, Diana M.
    Denholtz, Matthew
    Smits, Shirley
    Holterman, Lennart
    Damen, Irma
    Vogels, Ronald
    Thorner, Anna R.
    O'Brien, Kara L.
    Carville, Angela
    Mansfield, Keith G.
    Goudsmit, Jaap
    Havenga, Menzo J. E.
    Barouch, Dan H.
    [J]. JOURNAL OF VIROLOGY, 2007, 81 (09) : 4654 - 4663
  • [2] The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice
    Bao, Linlin
    Deng, Wei
    Huang, Baoying
    Gao, Hong
    Liu, Jiangning
    Ren, Lili
    Wei, Qiang
    Yu, Pin
    Xu, Yanfeng
    Qi, Feifei
    Qu, Yajin
    Li, Fengdi
    Lv, Qi
    Wang, Wenling
    Xue, Jing
    Gong, Shuran
    Liu, Mingya
    Wang, Guanpeng
    Wang, Shunyi
    Song, Zhiqi
    Zhao, Linna
    Liu, Peipei
    Zhao, Li
    Ye, Fei
    Wang, Huijuan
    Zhou, Weimin
    Zhu, Na
    Zhen, Wei
    Yu, Haisheng
    Zhang, Xiaojuan
    Guo, Li
    Chen, Lan
    Wang, Conghui
    Wang, Ying
    Wang, Xinming
    Xiao, Yan
    Sun, Qiangming
    Liu, Hongqi
    Zhu, Fanli
    Ma, Chunxia
    Yan, Lingmei
    Yang, Mengli
    Han, Jun
    Xu, Wenbo
    Tan, Wenjie
    Peng, Xiaozhong
    Jin, Qi
    Wu, Guizhen
    Qin, Chuan
    [J]. NATURE, 2020, 583 (7818) : 830 - +
  • [3] Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19
    Blanco-Melo, Daniel
    Nilsson-Payant, Benjamin E.
    Liu, Wen-Chun
    Uhl, Skyler
    Hoagland, Daisy
    Moller, Rasmus
    Jordan, Tristan X.
    Oishi, Kohei
    Panis, Maryline
    Sachs, David
    Wang, Taia T.
    Schwartz, Robert E.
    Lim, Jean K.
    Albrecht, Randy A.
    tenOever, Benjamin R.
    [J]. CELL, 2020, 181 (05) : 1036 - +
  • [4] High-throughput, multiplexed IgG subclassing of antigen-specific antibodies from clinical samples
    Brown, Eric P.
    Licht, Anna F.
    Dugast, Anne-Sophie
    Choi, Ickwon
    Bailey-Kellogg, Chris
    Alter, Galit
    Ackerman, Margaret E.
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 2012, 386 (1-2) : 117 - 123
  • [5] Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility
    Chan, Jasper Fuk-Woo
    Zhang, Anna Jinxia
    Yuan, Shuofeng
    Poon, Vincent Kwok-Man
    Chan, Chris Chung-Sing
    Lee, Andrew Chak-Yiu
    Chan, Wan-Mui
    Fan, Zhimeng
    Tsoi, Hoi-Wah
    Wen, Lei
    Liang, Ronghui
    Cao, Jianli
    Chen, Yanxia
    Tang, Kaiming
    Luo, Cuiting
    Cai, Jian-Piao
    Kok, Kin-Hang
    Chu, Hin
    Chan, Kwok-Hung
    Sridhar, Siddharth
    Chen, Zhiwei
    Chen, Honglin
    To, Kelvin Kai-Wang
    Yuen, Kwok-Yung
    [J]. CLINICAL INFECTIOUS DISEASES, 2020, 71 (09) : 2428 - 2446
  • [6] SARS-CoV-2 infection protects against rechallenge in rhesus macaques
    Chandrashekar, Abishek
    Liu, Jinyan
    Martinot, Amanda J.
    McMahan, Katherine
    Mercado, Noe B.
    Peter, Lauren
    Tostanoski, Lisa H.
    Yu, Jingyou
    Maliga, Zoltan
    Nekorchuk, Michael
    Busman-Sahay, Kathleen
    Terry, Margaret
    Wrijil, Linda M.
    Ducat, Sarah
    Martinez, David R.
    Atyeo, Caroline
    Fischinger, Stephanie
    Burke, John S.
    Slein, Matthew D.
    Pessaint, Laurent
    Van Ry, Alex
    Greenhouse, Jack
    Taylor, Tammy
    Blade, Kelvin
    Cook, Anthony
    Finneyfrock, Brad
    Brown, Renita
    Teow, Elyse
    Velasco, Jason
    Zahn, Roland
    Wegmann, Frank
    Abbink, Peter
    Bondzie, Esther A.
    Dagotto, Gabriel
    Gebre, Makda S.
    He, Xuan
    Jacob-Dolan, Catherine
    Kordana, Nicole
    Li, Zhenfeng
    Lifton, Michelle A.
    Mahrokhian, Shant H.
    Maxfield, Lori F.
    Nityanandam, Ramya
    Nkolola, Joseph P.
    Schmidt, Aaron G.
    Miller, Andrew D.
    Baric, Ralph S.
    Alter, Galit
    Sorger, Peter K.
    Estes, Jacob D.
    [J]. SCIENCE, 2020, 369 (6505) : 812 - +
  • [7] Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology
    Chung, Amy W.
    Kumar, Manu P.
    Arnold, Kelly B.
    Yu, Wen Han
    Schoen, Matthew K.
    Dunphy, Laura J.
    Suscovich, Todd J.
    Frahm, Nicole
    Linde, Caitlyn
    Mahan, Alison E.
    Hoffner, Michelle
    Streeck, Hendrik
    Ackerman, Margaret E.
    McElrath, M. Juliana
    Schuitemaker, Hanneke
    Pau, Maria G.
    Baden, Lindsey R.
    Kim, Jerome H.
    Michael, Nelson L.
    Barouch, Dan H.
    Lauffenburger, Douglas A.
    Alter, Galit
    [J]. CELL, 2015, 163 (04) : 988 - 998
  • [8] A high-throughput, bead-based, antigen-specific assay to assess the ability of antibodies to induce complement activation
    Fischinger, Stephanie
    Fallon, Jonathan K.
    Michell, Ashlin R.
    Broge, Thomas
    Suscovich, Todd J.
    Streeck, Hendrik
    Alter, Galit
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 2019, 473
  • [9] Development of an inactivated vaccine candidate for SARS-CoV-2
    Gao, Qiang
    Bao, Linlin
    Mao, Haiyan
    Wang, Lin
    Xu, Kangwei
    Yang, Minnan
    Li, Yajing
    Zhu, Ling
    Wang, Nan
    Lv, Zhe
    Gao, Hong
    Ge, Xiaoqin
    Kan, Biao
    Hu, Yaling
    Liu, Jiangning
    Cai, Fang
    Jiang, Deyu
    Yin, Yanhui
    Qin, Chengfeng
    Li, Jing
    Gong, Xuejie
    Lou, Xiuyu
    Shi, Wen
    Wu, Dongdong
    Zhang, Hengming
    Zhu, Lang
    Deng, Wei
    Li, Yurong
    Lu, Jinxing
    Li, Changgui
    Wang, Xiangxi
    Yin, Weidong
    Zhang, Yanjun
    Qin, Chuan
    [J]. SCIENCE, 2020, 369 (6499) : 77 - +
  • [10] Huang CL, 2020, LANCET, V395, P497, DOI [10.1016/S0140-6736(20)30183-5, 10.1016/S0140-6736(20)30211-7]