Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery

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

doi:10.3389/fviro.2022.891540

Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery

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. ShreiberJonathan 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

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	891540
Journal	Frontiers in Virology
Volume	2
DOIs	https://doi.org/10.3389/fviro.2022.891540
State	Published - 2022

Keywords

antibody
Bi-cistronic DNA vaccine
SARS-CoV-2
SARS-CoV-2 variant of concern
T cell
viral challenge

ASJC Scopus subject areas

Applied Microbiology and Biotechnology
Microbiology
Virology
Infectious Diseases

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10.3389/fviro.2022.891540

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Jeong, M., Kudchodkar, S. B., Gil, A., Jeon, B., Park, G. H., Cho, Y., Lee, H., Cheong, M. S., Kim, W., Hwang, Y. H., Lee, J. A., Lim, H., Kim, M. Y., Lallow, E. O., Brahmbhatt, T., Kania, S. A., Jhumur, N. C., Shan, J. W., Zahn, J. D., ... Maslow, J. N. (2022). Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery. Frontiers in Virology, 2, Article 891540. https://doi.org/10.3389/fviro.2022.891540

Jeong, M, Kudchodkar, SB, Gil, A, Jeon, B, Park, GH, Cho, Y, Lee, H, Cheong, MS, Kim, W, Hwang, YH, Lee, JA, Lim, H, Kim, MY, Lallow, EO, Brahmbhatt, T, Kania, SA, Jhumur, NC, Shan, JW, Zahn, JD, Shreiber, DI, Singer, JP, Lin, H, Spiegel, EK, Pessaint, L, Porto, M, Van Ry, A, Nase, D, Kar, S, Andersen, H, Tietjen, I, Cassel, J, Salvino, JM, Montaner, LJ, Park, YK, Muthumani, K, Roberts, CC & Maslow, JN 2022, 'Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery', Frontiers in Virology, vol. 2, 891540. https://doi.org/10.3389/fviro.2022.891540

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title = "Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery",

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.",

keywords = "antibody, Bi-cistronic DNA vaccine, SARS-CoV-2, SARS-CoV-2 variant of concern, T cell, viral challenge",

author = "Moonsup Jeong and Kudchodkar, {Sagar B.} and Areum Gil and Bohyun Jeon and Park, {Gee Ho} and Youngran Cho and Hyojin Lee and Cheong, {Mi Sun} and Wonil Kim and Hwang, {Yun Ho} and Lee, {Jung Ah} and Heeji Lim and Kim, {Mi Young} and Lallow, {Emran O.} and Tej Brahmbhatt and Kania, {Stephen A.} and Jhumur, {Nandita C.} and Shan, {Jerry W.} and Zahn, {Jeffrey D.} and Shreiber, {David I.} and Singer, {Jonathan P.} and Hao Lin and Spiegel, {Erin K.} and Laurent Pessaint and Maciel Porto and {Van Ry}, Alex and Danielle Nase and Swagata Kar and Hanne Andersen and Ian Tietjen and Joel Cassel and Salvino, {Joseph M.} and Montaner, {Luis J.} and Park, {Young K.} and Kar Muthumani and Roberts, {Christine C.} and Maslow, {Joel N.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 Jeong, Kudchodkar, Gil, Jeon, Park, Cho, Lee, Cheong, Kim, Hwang, Lee, Lim, Kim, Lallow, Brahmbhatt, Kania, Jhumur, Shan, Zahn, Shreiber, Singer, Lin, Spiegel, Pessaint, Porto, Van Ry, Nase, Kar, Andersen, Tietjen, Cassel, Salvino, Montaner, Park, Muthumani, Roberts and Maslow.",

year = "2022",

doi = "10.3389/fviro.2022.891540",

language = "English (US)",

volume = "2",

journal = "Frontiers in Virology",

issn = "2673-818X",

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TY - JOUR

T1 - Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery

AU - Jeong, Moonsup

AU - Kudchodkar, Sagar B.

AU - Gil, Areum

AU - Jeon, Bohyun

AU - Park, Gee Ho

AU - Cho, Youngran

AU - Lee, Hyojin

AU - Cheong, Mi Sun

AU - Kim, Wonil

AU - Hwang, Yun Ho

AU - Lee, Jung Ah

AU - Lim, Heeji

AU - Kim, Mi Young

AU - Lallow, Emran O.

AU - Brahmbhatt, Tej

AU - Kania, Stephen A.

AU - Jhumur, Nandita C.

AU - Shan, Jerry W.

AU - Zahn, Jeffrey D.

AU - Shreiber, David I.

AU - Singer, Jonathan P.

AU - Lin, Hao

AU - Spiegel, Erin K.

AU - Pessaint, Laurent

AU - Porto, Maciel

AU - Van Ry, Alex

AU - Nase, Danielle

AU - Kar, Swagata

AU - Andersen, Hanne

AU - Tietjen, Ian

AU - Cassel, Joel

AU - Salvino, Joseph M.

AU - Montaner, Luis J.

AU - Park, Young K.

AU - Muthumani, Kar

AU - Roberts, Christine C.

AU - Maslow, Joel N.

N1 - Publisher Copyright: Copyright © 2022 Jeong, Kudchodkar, Gil, Jeon, Park, Cho, Lee, Cheong, Kim, Hwang, Lee, Lim, Kim, Lallow, Brahmbhatt, Kania, Jhumur, Shan, Zahn, Shreiber, Singer, Lin, Spiegel, Pessaint, Porto, Van Ry, Nase, Kar, Andersen, Tietjen, Cassel, Salvino, Montaner, Park, Muthumani, Roberts and Maslow.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - antibody

KW - Bi-cistronic DNA vaccine

KW - SARS-CoV-2

KW - SARS-CoV-2 variant of concern

KW - T cell

KW - viral challenge

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DO - 10.3389/fviro.2022.891540

M3 - Article

AN - SCOPUS:85194059972

SN - 2673-818X

VL - 2

JO - Frontiers in Virology

JF - Frontiers in Virology

M1 - 891540

ER -

Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery

Abstract

Keywords

ASJC Scopus subject areas

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