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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Published inFrontiers in virology (online) Vol. 2
Main Authors Jeong, Moonsup, Kudchodkar, Sagar B., Gil, Areum, Jeon, Bohyun, Park, Gee Ho, Cho, Youngran, Lee, Hyojin, Cheong, Mi Sun, Kim, Wonil, Hwang, Yun-Ho, Lee, Jung-Ah, Lim, Heeji, Kim, Mi Young, Lallow, Emran O., Brahmbhatt, Tej, Kania, Stephen A., Jhumur, Nandita C., Shan, Jerry W., Zahn, Jeffrey D., Shreiber, David I., Singer, Jonathan P., Lin, Hao, Spiegel, Erin K., Pessaint, Laurent, Porto, Maciel, Van Ry, Alex, Nase, Danielle, Kar, Swagata, Andersen, Hanne, Tietjen, Ian, Cassel, Joel, Salvino, Joseph M., Montaner, Luis J., Park, Young K., Muthumani, Kar, Roberts, Christine C., Maslow, Joel N.
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 24.05.2022
Subjects
antibody
Bi-cistronic DNA vaccine
SARS-CoV-2
SARS-CoV-2 variant of concern
T cell
viral challenge
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Abstract 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.
AbstractList 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.
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.
Author Lee, Hyojin
Brahmbhatt, Tej
Jeong, Moonsup
Singer, Jonathan P.
Salvino, Joseph M.
Kania, Stephen A.
Tietjen, Ian
Lin, Hao
Porto, Maciel
Gil, Areum
Hwang, Yun-Ho
Van Ry, Alex
Lallow, Emran O.
Lim, Heeji
Cassel, Joel
Spiegel, Erin K.
Pessaint, Laurent
Montaner, Luis J.
Muthumani, Kar
Kim, Mi Young
Shreiber, David I.
Roberts, Christine C.
Park, Gee Ho
Maslow, Joel N.
Cho, Youngran
Zahn, Jeffrey D.
Andersen, Hanne
Cheong, Mi Sun
Jhumur, Nandita C.
Kim, Wonil
Nase, Danielle
Shan, Jerry W.
Jeon, Bohyun
Kar, Swagata
Lee, Jung-Ah
Kudchodkar, Sagar B.
Park, Young K.
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Snippet 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...
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SubjectTerms antibody
Bi-cistronic DNA vaccine
SARS-CoV-2
SARS-CoV-2 variant of concern
T cell
viral challenge
Title Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery
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