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

被引：68

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

共 59 条

[1] Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients A Phase 2, Randomized Clinical Trial [J].

Aldoss, Ibrahim ;

La Rosa, Corinna ;

Baden, Lindsey R. ;

Longmate, Jeffrey ;

Ariza-Heredia, Ella J. ;

Rida, Wasima N. ;

Lingaraju, Chetan Raj ;

Zhou, Qiao ;

Martinez, Joy ;

Kaltcheva, Teodora ;

Dagis, Andy ;

Hardwick, Nicola ;

Issa, Nicolas C. ;

Farol, Len ;

Nademanee, Auayporn ;

Al Malki, Monzr M. ;

Forman, Stephen ;

Nakamura, Ryotaro ;

Diamond, Don J. .

ANNALS OF INTERNAL MEDICINE, 2020, 172 (05) :306-+

[2] The complete genomic sequence of the modified vaccinia Ankara strain: Comparison with other orthopoxviruses [J].

Antoine, G ;

Scheiflinger, F ;

Dorner, F ;

Falkner, FG .

VIROLOGY, 1998, 244 (02) :365-396

[3] STRUCTURE AND REPLICATION OF VACCINIA VIRUS TELOMERES [J].

BAROUDY, BM ;

VENKATESAN, S ;

MOSS, B .

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1982, 47 :723-729

[4]

Birnboim H. C., 1979, NUCLEIC ACIDS RES, V7, P1513

[5] Host range and cytopathogenicity of the highly attenuated MVA strain of vaccinia virus: Propagation and generation of recombinant viruses in a nonhuman mammalian cell line [J].

Carroll, MW ;

Moss, B .

VIROLOGY, 1997, 238 (02) :198-211

[6] Multiantigenic Modified Vaccinia Virus Ankara Vaccine Vectors To Elicit Potent Humoral and Cellular Immune Reponses against Human Cytomegalovirus in Mice [J].

Chiuppesi, Flavia ;

Nguyen, Jenny ;

Park, Soojin ;

Contreras, Heidi ;

Kha, Mindy ;

Meng, Zhuo ;

Kaltcheva, Teodora ;

Iniguez, Angelina ;

Martinez, Joy ;

La Rosa, Corinna ;

Wussow, Felix ;

Diamond, Don J. .

JOURNAL OF VIROLOGY, 2018, 92 (19)

[7] Recombinant MVA vaccines: dispelling the myths [J].

Cottingham, Matthew G. ;

Carroll, Miles W. .

VACCINE, 2013, 31 (39) :4247-4251

[8] Recombination-Mediated Genetic Engineering of a Bacterial Artificial Chromosome Clone of Modified Vaccinia virus Ankara (MVA) [J].

Cottingham, Matthew G. ;

Andersen, Rikke F. ;

Spencer, Alexandra J. ;

Saurya, Saroj ;

Furze, Julie ;

Hill, Adrian V. S. ;

Gilbert, Sarah C. .

PLOS ONE, 2008, 3 (02)

[9] Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays [J].

Crawford, Katharine H. D. ;

Eguia, Rachel ;

Dingens, Adam S. ;

Loes, Andrea N. ;

Malone, Keara D. ;

Wolf, Caitlin R. ;

Chu, Helen Y. ;

Tortorici, M. Alejandra ;

Veesler, David ;

Murphy, Michael ;

Pettie, Deleah ;

King, Neil P. ;

Balazs, Alejandro B. ;

Bloom, Jesse D. .

VIRUSES-BASEL, 2020, 12 (05)

[10] Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development [J].

de Alwis, Ruklanthi ;

Chen, Shiwei ;

Gan, Esther S. ;

Ooi, Eng Eong .

EBIOMEDICINE, 2020, 55

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