A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs

被引：65

作者：

Routhu, Nanda Kishore ^{[1
,2
]}

Cheedarla, Narayanaiah ^{[1
,2
]}

Gangadhara, Sailaja ^{[1
,2
]}

Bollimpelli, Venkata Satish ^{[1
,2
]}

Boddapati, Arun K. ^{[1
,3
]}

Shiferaw, Ayalnesh ^{[1
,2
]}

Rahman, Sheikh Abdul ^{[1
,2
]}

Sahoo, Anusmita ^{[1
,2
]}

Edara, Venkata Viswanadh ^{[1
,4
]}

Lai, Lilin ^{[1
,4
]}

Floyd, Katharine ^{[1
,4
]}

Wang, Shelly ^{[1
]}

Fischinger, Stephanie ^{[5
]}

Atyeo, Caroline ^{[5
]}

Shin, Sally A. ^{[5
]}

Gumber, Sanjeev ^{[6
]}

Kirejczyk, Shannon ^{[6
]}

Cohen, Joyce ^{[7
]}

Jean, Sherrie M. ^{[7
]}

Wood, Jennifer S. ^{[7
]}

Connor-Stroud, Fawn ^{[7
]}

Stammen, Rachelle L. ^{[7
]}

Upadhyay, Amit A. ^{[1
]}

Pellegrini, Kathryn ^{[1
]}

Montefiori, David ^{[8
]}

Shi, Pei-Yong ^{[9
]}

Menachery, Vineet D. ^{[10
]}

Alter, Galit ^{[5
]}

Vanderford, Thomas H. ^{[1
]}

Bosinger, Steven E. ^{[1
,3
]}

Suthar, Mehul S. ^{[1
,4
]}

Amara, Rama Rao ^{[1
,2
]}

机构：

[1] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Div Microbiol & Immunol, Atlanta, GA 30329 USA

[2] Emory Univ, Emory Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

[3] Emory Univ, Emory Sch Med, Dept Pathol, Atlanta, GA 30322 USA

[4] Emory Univ, Sch Med, Dept Pediat, Div Infect Dis, Atlanta, GA 30322 USA

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

[6] Emory Univ, Yerkes Natl Primate Res Ctr, Div Pathol, Atlanta, GA 30329 USA

[7] Emory Univ, Yerkes Natl Primate Res Ctr, Div Anim Resources, Atlanta, GA 30329 USA

[8] Duke Univ, Sch Med, Dept Surg, Durham, NC 27710 USA

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

[10] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

来源：

IMMUNITY | 2021年 / 54卷 / 03期

基金：

美国国家卫生研究院;

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; ANTIBODY-RESPONSES; MUCOSAL CHALLENGE; HIGH-THROUGHPUT; IMMUNOGENICITY; HIV-1; ANTIGEN; SPIKE; MVA; DNA;

D O I：

10.1016/j.immuni.2021.02.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8(+) T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8(+) T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.

引用

页码：542 / +

页数：24

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