Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques

被引:40
作者
He, Xuan [1 ]
Chandrashekar, Abishek [1 ]
Zahn, Roland [3 ]
Wegmann, Frank [3 ]
Yu, Jingyou [1 ]
Mercado, Noe B. [1 ]
McMahan, Katherine [1 ]
Martinot, Amanda J. [2 ]
Piedra-Mora, Cesar [2 ]
Beecy, Sidney [2 ]
Ducat, Sarah [2 ]
Chamanza, Ronnie [3 ]
Huber, Sietske Rosendahl [3 ]
van Heerden, Marjolein [3 ]
van der Fits, Leslie [3 ]
Borducchi, Erica N. [1 ]
Lifton, Michelle [1 ]
Liu, Jinyan [1 ]
Nampanya, Felix [1 ]
Patel, Shivani [1 ]
Peter, Lauren [1 ]
Tostanoski, Lisa H. [1 ]
Pessaint, Laurent [4 ]
Van Ry, Alex [4 ]
Finneyfrock, Brad [4 ]
Velasco, Jason [4 ]
Teow, Elyse [4 ]
Brown, Renita [4 ]
Cook, Anthony [4 ]
Andersen, Hanne [4 ]
Lewis, Mark G. [4 ]
Schuitemaker, Hanneke [3 ]
Barouch, Dan H. [1 ,5 ,6 ]
机构
[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA
[2] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA 01536 USA
[3] Janssen Vaccines & Prevent BV, Leiden, Netherlands
[4] Bioqual, Rockville, MD 20852 USA
[5] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA
[6] Massachusetts Consortium Pathogen Readiness, Boston, MA 02215 USA
基金
美国国家卫生研究院;
关键词
CELLS;
D O I
10.1016/j.cell.2021.05.040
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
We previously reported that a single immunization with an adenovirus serotype 26 (Ad26)-vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. To evaluate reduced doses of Ad26.COV2.S, 30 rhesus macaques were immunized once with 1 x 10(11), 5 x 10(10), 1.125 x 10(10), or 2 x 10(9) viral particles (vp) Ad26.COV2.S or sham and were challenged with SARS-CoV-2. Vaccine doses as low as 2 x 10(9) vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125 x 10(10) vp were required for protection in nasal swabs. Activated memory B cells and binding or neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show enhancement of disease, These data demonstrate that a single immunization with relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques, although a higher vaccine dose may be required for protection in the upper respiratory tract.
引用
收藏
页码:3467 / +
页数:18
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