Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform.
| Title: | Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform. |
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| Authors: | Chiuppesi F; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Salazar MD; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Contreras H; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Nguyen VH; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Martinez J; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Park Y; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Nguyen J; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Kha M; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Iniguez A; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Zhou Q; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Kaltcheva T; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Levytskyy R; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA.; Ebelt ND; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.; Kang TH; Integrative Genomics Core, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.; Wu X; Integrative Genomics Core, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.; Rogers TF; Division of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA, 92093, USA.; Scripps Research, Department of Immunology and Microbiology, 10550N Torrey Pines Rd, La Jolla, CA, 92037, USA.; Manuel ER; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.; Shostak Y; Research Business Development, City of Hope, Duarte, CA, 91010, USA.; Diamond DJ; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA. ddiamond@coh.org.; Wussow F; Department of Hematology and Transplant Center, City of Hope National Medical Center, Duarte, CA, 91010, USA. fwussow@coh.org. |
| Source: | Nature communications [Nat Commun] 2020 Nov 30; Vol. 11 (1), pp. 6121. Date of Electronic Publication: 2020 Nov 30. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | COVID-19 Vaccines/*immunology ; Coronavirus Nucleocapsid Proteins/*immunology ; Spike Glycoprotein, Coronavirus/*immunology ; Vaccines, Synthetic/*immunology; Antibodies, Viral/immunology ; Antigens, Viral/immunology ; Genetic Vectors/immunology ; Phosphoproteins/immunology ; SARS-CoV-2/immunology ; Vaccines, Attenuated/immunology ; Vaccinia virus/immunology ; Viral Vaccines/immunology ; Adaptive Immunity ; Animals ; Antibodies, Neutralizing ; Humans ; Immunity, Cellular ; Mice |
| Abstract: | 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. |
| Comments: | Update of: bioRxiv. 2020 Jul 02:2020.07.01.183236. doi: 10.1101/2020.07.01.183236.. (PMID: 32637957); Update of: Res Sq. 2020 Jul 17:rs.3.rs-40198. doi: 10.21203/rs.3.rs-40198/v1.. (PMID: 32702732) |
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| Grant Information: | U19 AI128913 United States AI NIAID NIH HHS; R01 CA181045 United States CA NCI NIH HHS; P30 CA033572 United States CA NCI NIH HHS; P50 CA107399 United States CA NCI NIH HHS; P30 AI036214 United States AI NIAID NIH HHS; P01 CA111412 United States CA NCI NIH HHS |
| Substance Nomenclature: | 0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (COVID-19 Vaccines); 0 (Coronavirus Nucleocapsid Proteins); 0 (Phosphoproteins); 0 (Spike Glycoprotein, Coronavirus); 0 (Vaccines, Attenuated); 0 (Vaccines, Synthetic); 0 (Viral Vaccines); 0 (nucleocapsid phosphoprotein, SARS-CoV-2); 0 (spike protein, SARS-CoV-2) |
| Entry Date(s): | Date Created: 20201201 Date Completed: 20201218 Latest Revision: 20241122 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7705736 |
| DOI: | 10.1038/s41467-020-19819-1 |
| PMID: | 33257686 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't