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Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogen...

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Autores principales: Rosati, Margherita, Agarwal, Mahesh, Hu, Xintao, Devasundaram, Santhi, Stellas, Dimitris, Chowdhury, Bhabadeb, Bear, Jenifer, Burns, Robert, Donohue, Duncan, Pessaint, Laurent, Andersen, Hanne, Lewis, Mark G., Terpos, Evangelos, Dimopoulos, Meletios Athanasios, Wlodawer, Alexander, Mullins, James I., Venzon, David J., Pavlakis, George N., Felber, Barbara K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489704/
https://www.ncbi.nlm.nih.gov/pubmed/34551020
http://dx.doi.org/10.1371/journal.ppat.1009701
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author Rosati, Margherita
Agarwal, Mahesh
Hu, Xintao
Devasundaram, Santhi
Stellas, Dimitris
Chowdhury, Bhabadeb
Bear, Jenifer
Burns, Robert
Donohue, Duncan
Pessaint, Laurent
Andersen, Hanne
Lewis, Mark G.
Terpos, Evangelos
Dimopoulos, Meletios Athanasios
Wlodawer, Alexander
Mullins, James I.
Venzon, David J.
Pavlakis, George N.
Felber, Barbara K.
author_facet Rosati, Margherita
Agarwal, Mahesh
Hu, Xintao
Devasundaram, Santhi
Stellas, Dimitris
Chowdhury, Bhabadeb
Bear, Jenifer
Burns, Robert
Donohue, Duncan
Pessaint, Laurent
Andersen, Hanne
Lewis, Mark G.
Terpos, Evangelos
Dimopoulos, Meletios Athanasios
Wlodawer, Alexander
Mullins, James I.
Venzon, David J.
Pavlakis, George N.
Felber, Barbara K.
author_sort Rosati, Margherita
collection PubMed
description The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The antibodies recognized and potently neutralized a panel of different Spike variants including Alpha, Delta, Epsilon, Eta and A.23.1, but to a lesser extent Beta and Gamma. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques.
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spelling pubmed-84897042021-10-05 Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques Rosati, Margherita Agarwal, Mahesh Hu, Xintao Devasundaram, Santhi Stellas, Dimitris Chowdhury, Bhabadeb Bear, Jenifer Burns, Robert Donohue, Duncan Pessaint, Laurent Andersen, Hanne Lewis, Mark G. Terpos, Evangelos Dimopoulos, Meletios Athanasios Wlodawer, Alexander Mullins, James I. Venzon, David J. Pavlakis, George N. Felber, Barbara K. PLoS Pathog Research Article The speed of development, versatility and efficacy of mRNA-based vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA vaccines represent an important alternative since they induce both humoral and cellular immune responses in animal models and in human trials. We tested the immunogenicity and protective efficacy of DNA-based vaccine regimens expressing different prefusion-stabilized Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection followed by electroporation in rhesus macaques. Different Spike DNA vaccine regimens induced antibodies that potently neutralized SARS-CoV-2 in vitro and elicited robust T cell responses. The antibodies recognized and potently neutralized a panel of different Spike variants including Alpha, Delta, Epsilon, Eta and A.23.1, but to a lesser extent Beta and Gamma. The DNA-only vaccine regimens were compared to a regimen that included co-immunization of Spike DNA and protein in the same anatomical site, the latter of which showed significant higher antibody responses. All vaccine regimens led to control of SARS-CoV-2 intranasal/intratracheal challenge and absence of virus dissemination to the lower respiratory tract. Vaccine-induced binding and neutralizing antibody titers and antibody-dependent cellular phagocytosis inversely correlated with transient virus levels in the nasal mucosa. Importantly, the Spike DNA+Protein co-immunization regimen induced the highest binding and neutralizing antibodies and showed the strongest control against SARS-CoV-2 challenge in rhesus macaques. Public Library of Science 2021-09-22 /pmc/articles/PMC8489704/ /pubmed/34551020 http://dx.doi.org/10.1371/journal.ppat.1009701 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Rosati, Margherita
Agarwal, Mahesh
Hu, Xintao
Devasundaram, Santhi
Stellas, Dimitris
Chowdhury, Bhabadeb
Bear, Jenifer
Burns, Robert
Donohue, Duncan
Pessaint, Laurent
Andersen, Hanne
Lewis, Mark G.
Terpos, Evangelos
Dimopoulos, Meletios Athanasios
Wlodawer, Alexander
Mullins, James I.
Venzon, David J.
Pavlakis, George N.
Felber, Barbara K.
Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques
title Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques
title_full Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques
title_fullStr Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques
title_full_unstemmed Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques
title_short Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques
title_sort control of sars-cov-2 infection after spike dna or spike dna+protein co-immunization in rhesus macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489704/
https://www.ncbi.nlm.nih.gov/pubmed/34551020
http://dx.doi.org/10.1371/journal.ppat.1009701
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