Correlates of protection against SARS-CoV-2 in rhesus macaques

被引：830

作者：

McMahan, Katherine ^{[1
]}

Yu, Jingyou ^{[1
]}

Mercado, Noe B. ^{[1
]}

Loos, Carolin ^{[2
,3
]}

Tostanoski, Lisa H. ^{[1
]}

Chandrashekar, Abishek ^{[1
]}

Liu, Jinyan ^{[1
]}

Peter, Lauren ^{[1
]}

Atyeo, Caroline ^{[2
,4
]}

Zhu, Alex ^{[2
]}

Bondzie, Esther A. ^{[1
]}

Dagotto, Gabriel ^{[1
,4
]}

Gebre, Makda S. ^{[1
,4
]}

Jacob-Dolan, Catherine ^{[1
,4
]}

Li, Zhenfeng ^{[1
]}

Nampanya, Felix ^{[1
]}

Patel, Shivani ^{[1
]}

Pessaint, Laurent ^{[5
]}

Van Ry, Alex ^{[5
]}

Blade, Kelvin ^{[5
]}

Yalley-Ogunro, Jake ^{[5
]}

Cabus, Mehtap ^{[5
]}

Brown, Renita ^{[5
]}

Cook, Anthony ^{[5
]}

Teow, Elyse ^{[5
]}

Andersen, Hanne ^{[5
]}

Lewis, Mark G. ^{[5
]}

Lauffenburger, Douglas A. ^{[3
]}

Alter, Galit ^{[2
,6
]}

Barouch, Dan H. ^{[1
,2
,4
,6
]}

机构：

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

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

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

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

[5] Bioqual, Rockville, MD USA

[6] Massachusetts Consortium Pathogen Readiness, Boston, MA USA

来源：

NATURE | 2021年 / 590卷 / 7847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：

IMMUNITY;

D O I：

10.1038/s41586-020-03041-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Adoptive transfer of purified IgG from convalescent macaques protects naive macaques against SARS-CoV-2 infection, and cellular immune responses contribute to protection against rechallenge with SARS-CoV-2. Recent studies have reported the protective efficacy of both natural(1) and vaccine-induced(2-7) immunity against challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rhesus macaques. However, the importance of humoral and cellular immunity for protection against infection with SARS-CoV-2 remains to be determined. Here we show that the adoptive transfer of purified IgG from convalescent rhesus macaques (Macaca mulatta) protects naive recipient macaques against challenge with SARS-CoV-2 in a dose-dependent fashion. Depletion of CD8(+) T cells in convalescent macaques partially abrogated the protective efficacy of natural immunity against rechallenge with SARS-CoV-2, which suggests a role for cellular immunity in the context of waning or subprotective antibody titres. These data demonstrate that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may contribute to protection if antibody responses are suboptimal. We also show that higher antibody titres are required for treatment of SARS-CoV-2 infection in macaques. These findings have implications for the development of SARS-CoV-2 vaccines and immune-based therapeutic agents.

引用

页码：630 / 634

页数：20

共 17 条

[1] 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

[2] SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy [J].

Casadevall, Arturo ;

Joyner, Michael J. ;

Pirofski, Liise-anne .

JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (10) :5112-5114

[3] SARS-CoV-2 infection protects against rechallenge in rhesus macaques [J].

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. .

SCIENCE, 2020, 369 (6505) :812-+

[4] Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology [J].

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 .

CELL, 2015, 163 (04) :988-998

[5] Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates [J].

Corbett, Kizzmekia S. ;

Flynn, Barbara ;

Foulds, Kathryn E. ;

Francica, Joseph R. ;

Boyoglu-Barnum, Seyhan ;

Werner, Anne P. ;

Flach, Britta ;

O'Connell, Sarah ;

Bock, Kevin W. ;

Minai, Mahnaz ;

Nagata, Bianca M. ;

Andersen, Hanne ;

Martinez, David R. ;

Noe, Amy T. ;

Douek, Naomi ;

Donaldson, Mitzi M. ;

Nji, Nadesh N. ;

Alvarado, Gabriela S. ;

Edwards, Darin K. ;

Flebbe, Dillon R. ;

Lamb, Evan ;

Doria-Rose, Nicole A. ;

Lin, Bob C. ;

Louder, Mark K. ;

O'Dell, Sijy ;

Schmidt, Stephen D. ;

Phung, Emily ;

Chang, Lauren A. ;

Yap, Christina ;

Todd, John-Paul M. ;

Pessaint, Laurent ;

Van Ry, Alex ;

Browne, Shanai ;

Greenhouse, Jack ;

Putman-Taylor, Tammy ;

Strasbaugh, Amanda ;

Campbell, Tracey-Ann ;

Cook, Anthony ;

Dodson, Alan ;

Steingrebe, Katelyn ;

Shi, Wei ;

Zhang, Yi ;

Abiona, Olubukola M. ;

Wang, Lingshu ;

Pegu, Amarendra ;

Yang, Eun Sung ;

Leung, Kwanyee ;

Zhou, Tongqing ;

Teng, I-Ting ;

Widge, Alicia .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (16) :1544-1555

[6] Development of an inactivated vaccine candidate for SARS-CoV-2 [J].

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 .

SCIENCE, 2020, 369 (6499) :77-+

[7]

Joyner Michael J, 2020, medRxiv, DOI 10.1101/2020.08.12.20169359

[8] Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques [J].

Mercado, Noe B. ;

Zahn, Roland ;

Wegmann, Frank ;

Loos, Carolin ;

Chandrashekar, Abishek ;

Yu, Jingyou ;

Liu, Jinyan ;

Peter, Lauren ;

McMahan, Katherine ;

Tostanoski, Lisa H. ;

He, Xuan ;

Martinez, David R. ;

Rutten, Lucy ;

Bos, Rinke ;

van Manen, Danielle ;

Vellinga, Jort ;

Custers, Jerome ;

Langedijk, Johannes P. ;

Kwaks, Ted ;

Bakkers, Mark J. G. ;

Zuijdgeest, David ;

Rosendahl Huber, Sietske K. ;

Atyeo, Caroline ;

Fischinger, Stephanie ;

Burke, John S. ;

Feldman, Jared ;

Hauser, Blake M. ;

Caradonna, Timothy M. ;

Bondzie, Esther A. ;

Dagotto, Gabriel ;

Gebre, Makda S. ;

Hoffman, Emily ;

Jacob-Dolan, Catherine ;

Kirilova, Marinela ;

Li, Zhenfeng ;

Lin, Zijin ;

Mahrokhian, Shant H. ;

Maxfield, Lori F. ;

Nampanya, Felix ;

Nityanandam, Ramya ;

Nkolola, Joseph P. ;

Patel, Shivani ;

Ventura, John D. ;

Verrington, Kaylee ;

Wan, Huahua ;

Pessaint, Laurent ;

Van Ry, Alex ;

Blade, Kelvin ;

Strasbaugh, Amanda ;

Cabus, Mehtap .

NATURE, 2020, 586 (7830) :583-+

[9]

Robbiani Davide F, 2020, Nature, V584, P437, DOI [10.1101/2020.05.13.092619, 10.1038/s41586-020-2456-9]

[10] Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes [J].

Schmitz, JE ;

Kuroda, MJ ;

Santra, S ;

Sasseville, VG ;

Simon, MA ;

Lifton, MA ;

Racz, P ;

Tenner-Racz, K ;

Dalesandro, M ;

Scallon, BJ ;

Ghrayeb, J ;

Forman, MA ;

Montefiori, DC ;

Rieber, EP ;

Letvin, NL ;

Reimann, KA .

SCIENCE, 1999, 283 (5403) :857-860

← 1 2 →