Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5-based COVID-19 vaccine

被引：85

作者：

An, Dong ^{[1
]}

Li, Kun ^{[2
]}

Rowe, Dawne K. ^{[1
]}

Diaz, Maria Cristina Huertas ^{[1
]}

Griffin, Emily F. ^{[1
]}

Beavis, Ashley C. ^{[1
]}

Johnson, Scott K. ^{[3
]}

Padykula, Ian ^{[1
]}

Jones, Cheryl A. ^{[3
]}

Briggs, Kelsey ^{[1
]}

Li, Geng ^{[1
]}

Lin, Yuan ^{[1
]}

Huang, Jiachen ^{[1
]}

Mousa, Jarrod ^{[1
,3
]}

Brindley, Melinda ^{[1
]}

Sakamoto, Kaori ^{[4
]}

Meyerholz, David K. ^{[5
]}

McCray, Paul B., Jr. ^{[2
,6
]}

Tompkins, S. Mark ^{[1
,3
]}

He, Biao ^{[1
]}

机构：

[1] Univ Georgia, Dept Infect Dis, Coll Vet Med, Athens, GA 30602 USA

[2] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA

[3] Univ Georgia, Ctr Vaccines & Immunol, Coll Vet Med, Athens, GA 30602 USA

[4] Univ Georgia, Dept Pathol, Coll Vet Med, Athens, GA 30602 USA

[5] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA

[6] Univ Iowa, Dept Microbiol & Immunol, Iowa City, IA 52242 USA

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 27期

关键词：

INFECTION; HEMAGGLUTININ; INTRANASAL;

D O I：

10.1126/sciadv.abi5246

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：

Transmission-blocking vaccines are urgently needed to reduce transmission of SARS-CoV 2, the cause of the COVID-19 pandemic. The upper respiratory tract is an initial site of SARS-CoV-2 infection and, for many individuals, remains the primary site of virus replication. An ideal COVID-19 vaccine should reduce upper respiratory tract virus replication and block transmission as well as protect against severe disease. Here, we optimized a vaccine candidate, parainfluenza virus 5 (PIV5) expressing the SARS-CoV-2 S protein (CVXGA1), and then demonstrated that a single-dose intranasal immunization with CVXGA1 protects against lethal infection of K18-hACE2 mice, a severe disease model. CVXGA1 immunization also prevented virus infection of ferrets and blocked contact transmission. This mucosal vaccine strategy inhibited SARS-CoV-2 replication in the upper respiratory tract, thus preventing disease progression to the lower respiratory tract. A PIV5-based mucosal vaccine provides a strategy to induce protective innate and cellular immune responses and reduce SARS-CoV-2 infection and transmission in populations.

引用

页数：13

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