Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery
SARS-CoV-2 is the third pathogenic coronavirus to emerge since 2000. Experience from prior outbreaks of SARS-CoV and MERS-CoV has demonstrated the importance of both humoral and cellular immunity to clinical outcome, precepts that have been recapitulated for SARS-CoV-2. Despite the unprecedented rap...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Virology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fviro.2022.891540/full |
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| author | Moonsup Jeong Sagar B. Kudchodkar Areum Gil Bohyun Jeon Gee Ho Park Youngran Cho Hyojin Lee Mi Sun Cheong Wonil Kim Yun-Ho Hwang Jung-Ah Lee Heeji Lim Mi Young Kim Emran O. Lallow Tej Brahmbhatt Stephen A. Kania Nandita C. Jhumur Jerry W. Shan Jeffrey D. Zahn David I. Shreiber Jonathan P. Singer Hao Lin Erin K. Spiegel Laurent Pessaint Maciel Porto Alex Van Ry Danielle Nase Swagata Kar Hanne Andersen Ian Tietjen Joel Cassel Joseph M. Salvino Luis J. Montaner Young K. Park Kar Muthumani Christine C. Roberts Joel N. Maslow |
| author_facet | Moonsup Jeong Sagar B. Kudchodkar Areum Gil Bohyun Jeon Gee Ho Park Youngran Cho Hyojin Lee Mi Sun Cheong Wonil Kim Yun-Ho Hwang Jung-Ah Lee Heeji Lim Mi Young Kim Emran O. Lallow Tej Brahmbhatt Stephen A. Kania Nandita C. Jhumur Jerry W. Shan Jeffrey D. Zahn David I. Shreiber Jonathan P. Singer Hao Lin Erin K. Spiegel Laurent Pessaint Maciel Porto Alex Van Ry Danielle Nase Swagata Kar Hanne Andersen Ian Tietjen Joel Cassel Joseph M. Salvino Luis J. Montaner Young K. Park Kar Muthumani Christine C. Roberts Joel N. Maslow |
| author_sort | Moonsup Jeong |
| collection | DOAJ |
| description | SARS-CoV-2 is the third pathogenic coronavirus to emerge since 2000. Experience from prior outbreaks of SARS-CoV and MERS-CoV has demonstrated the importance of both humoral and cellular immunity to clinical outcome, precepts that have been recapitulated for SARS-CoV-2. Despite the unprecedented rapid development and deployment of vaccines against SARS-CoV-2, more vaccines are needed to meet global demand and to guard against immune evasion by newly emerging SARS-CoV-2 variants. Here we describe the development of pGO-1002, a novel bi-cistronic synthetic DNA vaccine that encodes consensus sequences of two SARS-CoV-2 antigens, Spike and ORF3a. Mice immunized with pGO-1002 developed humoral and cellular responses to both antigens, including antibodies and capable of neutralizing infection by a clinical SARS-CoV-2 isolate. Rats immunized with pGO-1002 by intradermal (ID) injection followed by application of suction with our GeneDerm device also developed humoral responses that included neutralizing antibodies and RBD-ACE2 blocking antibodies as well as robust cellular responses to both antigens. Significantly, in a Syrian hamster vaccination and challenge model, ID+GeneDerm-assisted vaccination prevented viral replication in the lungs and significantly reduced viral replication in the nares of hamsters challenged with either an ancestral SARS-CoV-2 strain or the B.1.351 (Beta) variant of concern. Furthermore, vaccinated immune sera inhibited virus-mediated cytopathic effects in vitro. These data establish the immunogenicity of the SARS-CoV-2 vaccine candidate pGO-1002 which induces potent humoral and cellular responses to the Spike and ORF3a antigens and may provide greater protection against emerging variants. |
| first_indexed | 2024-12-12T10:45:55Z |
| format | Article |
| id | doaj.art-c73deb36ca654fa2815416d4cd1e4dd1 |
| institution | Directory Open Access Journal |
| issn | 2673-818X |
| language | English |
| last_indexed | 2024-12-12T10:45:55Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Virology |
| spelling | doaj.art-c73deb36ca654fa2815416d4cd1e4dd12022-12-22T00:26:53ZengFrontiers Media S.A.Frontiers in Virology2673-818X2022-05-01210.3389/fviro.2022.891540891540Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction DeliveryMoonsup Jeong0Sagar B. Kudchodkar1Areum Gil2Bohyun Jeon3Gee Ho Park4Youngran Cho5Hyojin Lee6Mi Sun Cheong7Wonil Kim8Yun-Ho Hwang9Jung-Ah Lee10Heeji Lim11Mi Young Kim12Emran O. Lallow13Tej Brahmbhatt14Stephen A. Kania15Nandita C. Jhumur16Jerry W. Shan17Jeffrey D. Zahn18David I. Shreiber19Jonathan P. Singer20Hao Lin21Erin K. Spiegel22Laurent Pessaint23Maciel Porto24Alex Van Ry25Danielle Nase26Swagata Kar27Hanne Andersen28Ian Tietjen29Joel Cassel30Joseph M. Salvino31Luis J. Montaner32Young K. Park33Kar Muthumani34Christine C. Roberts35Joel N. Maslow36GeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaKorea Disease Control and Prevention Agency, Center for Vaccine Research, National Institute of Infectious Diseases, National Institute of Health, Cheongju-si, South KoreaKorea Disease Control and Prevention Agency, Center for Vaccine Research, National Institute of Infectious Diseases, National Institute of Health, Cheongju-si, South KoreaKorea Disease Control and Prevention Agency, Center for Vaccine Research, National Institute of Infectious Diseases, National Institute of Health, Cheongju-si, South KoreaKorea Disease Control and Prevention Agency, Center for Vaccine Research, National Institute of Infectious Diseases, National Institute of Health, Cheongju-si, South KoreaDepartment of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, United StatesDepartment of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, TN, United StatesDepartment of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, TN, United StatesDepartment of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, United StatesDepartment of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, United StatesDepartment of Biomedical Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, United StatesDepartment of Biomedical Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, United StatesDepartment of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, United StatesDepartment of Mechanical and Aerospace Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, United StatesPharmaJet, Inc., Golden, CO, United StatesBioqual, Rockville, MD, United StatesBioqual, Rockville, MD, United StatesBioqual, Rockville, MD, United StatesBioqual, Rockville, MD, United StatesBioqual, Rockville, MD, United StatesBioqual, Rockville, MD, United StatesVaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesVaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesVaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesVaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaGeneOne Life Science, Inc., Seoul, South KoreaSARS-CoV-2 is the third pathogenic coronavirus to emerge since 2000. Experience from prior outbreaks of SARS-CoV and MERS-CoV has demonstrated the importance of both humoral and cellular immunity to clinical outcome, precepts that have been recapitulated for SARS-CoV-2. Despite the unprecedented rapid development and deployment of vaccines against SARS-CoV-2, more vaccines are needed to meet global demand and to guard against immune evasion by newly emerging SARS-CoV-2 variants. Here we describe the development of pGO-1002, a novel bi-cistronic synthetic DNA vaccine that encodes consensus sequences of two SARS-CoV-2 antigens, Spike and ORF3a. Mice immunized with pGO-1002 developed humoral and cellular responses to both antigens, including antibodies and capable of neutralizing infection by a clinical SARS-CoV-2 isolate. Rats immunized with pGO-1002 by intradermal (ID) injection followed by application of suction with our GeneDerm device also developed humoral responses that included neutralizing antibodies and RBD-ACE2 blocking antibodies as well as robust cellular responses to both antigens. Significantly, in a Syrian hamster vaccination and challenge model, ID+GeneDerm-assisted vaccination prevented viral replication in the lungs and significantly reduced viral replication in the nares of hamsters challenged with either an ancestral SARS-CoV-2 strain or the B.1.351 (Beta) variant of concern. Furthermore, vaccinated immune sera inhibited virus-mediated cytopathic effects in vitro. These data establish the immunogenicity of the SARS-CoV-2 vaccine candidate pGO-1002 which induces potent humoral and cellular responses to the Spike and ORF3a antigens and may provide greater protection against emerging variants.https://www.frontiersin.org/articles/10.3389/fviro.2022.891540/fullSARS-CoV-2Bi-cistronic DNA vaccineT cellantibodySARS-CoV-2 variant of concernviral challenge |
| spellingShingle | Moonsup Jeong Sagar B. Kudchodkar Areum Gil Bohyun Jeon Gee Ho Park Youngran Cho Hyojin Lee Mi Sun Cheong Wonil Kim Yun-Ho Hwang Jung-Ah Lee Heeji Lim Mi Young Kim Emran O. Lallow Tej Brahmbhatt Stephen A. Kania Nandita C. Jhumur Jerry W. Shan Jeffrey D. Zahn David I. Shreiber Jonathan P. Singer Hao Lin Erin K. Spiegel Laurent Pessaint Maciel Porto Alex Van Ry Danielle Nase Swagata Kar Hanne Andersen Ian Tietjen Joel Cassel Joseph M. Salvino Luis J. Montaner Young K. Park Kar Muthumani Christine C. Roberts Joel N. Maslow Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery Frontiers in Virology SARS-CoV-2 Bi-cistronic DNA vaccine T cell antibody SARS-CoV-2 variant of concern viral challenge |
| title | Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery |
| title_full | Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery |
| title_fullStr | Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery |
| title_full_unstemmed | Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery |
| title_short | Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery |
| title_sort | immune responses of a novel bi cistronic sars cov 2 dna vaccine following intradermal immunization with suction delivery |
| topic | SARS-CoV-2 Bi-cistronic DNA vaccine T cell antibody SARS-CoV-2 variant of concern viral challenge |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2022.891540/full |
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