Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

被引：65

作者：

Chiuppesi, Flavia ^{[1
,2
]}

Salazar, Marcela d'Alincourt ^{[1
,2
]}

Contreras, Heidi ^{[1
,2
]}

Nguyen, Vu H. ^{[1
,2
]}

Martinez, Joy ^{[1
,2
]}

Park, Yoonsuh ^{[1
,2
]}

Nguyen, Jenny ^{[1
,2
]}

Kha, Mindy ^{[1
,2
]}

Iniguez, Angelina ^{[1
,2
]}

Zhou, Qiao ^{[1
,2
]}

Kaltcheva, Teodora ^{[1
,2
]}

Levytskyy, Roman ^{[1
,2
]}

Ebelt, Nancy D. ^{[3
]}

Kang, Tae Hyuk ^{[4
]}

Wu, Xiwei ^{[4
]}

Rogers, Thomas F. ^{[5
,6
]}

Manuel, Edwin R. ^{[3
]}

Shostak, Yuriy ^{[7
]}

Diamond, Don J. ^{[1
,2
]}

Wussow, Felix ^{[1
,2
]}

机构：

[1] City Hope Natl Med Ctr, Dept Hematol, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Transplant Ctr, Duarte, CA 91010 USA

[3] City Hope Natl Med Ctr, Dept Immunooncol, Beckman Res Inst, Duarte, CA 91010 USA

[4] City Hope Natl Med Ctr, Integrat Genom Core, Beckman Res Inst, Duarte, CA 91010 USA

[5] Univ Calif San Diego, Sch Med, Div Infect Dis & Global Publ Hlth, 9500 Gilman Dr, La Jolla, CA 92093 USA

[6] Scripps Res, Dept Immunol & Microbiol, 10550N Torrey Pines Rd, La Jolla, CA 92037 USA

[7] City Hope Natl Med Ctr, Res Business Dev, Duarte, CA 91010 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

VIRUS ANKARA; MOLECULAR-CLONING; GENOMIC SEQUENCE; STRAIN; DNA;

D O I：

10.1038/s41467-020-19819-1

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：

Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

引用

页数：16

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