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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.
  • Rosati M; Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Agarwal M; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Hu X; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Devasundaram S; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Stellas D; Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Chowdhury B; Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Bear J; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Burns R; Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.
  • Donohue D; MS Applied Information and Management Sciences, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
  • Pessaint L; BIOQUAL, Inc.; Rockville, Maryland, United States of America.
  • Andersen H; BIOQUAL, Inc.; Rockville, Maryland, United States of America.
  • Lewis MG; BIOQUAL, Inc.; Rockville, Maryland, United States of America.
  • Terpos E; Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
  • Dimopoulos MA; Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
  • Wlodawer A; Center for Structural Biology, National Cancer Institute, Frederick, Maryland, United States of America.
  • Mullins JI; Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
  • Venzon DJ; Department of Medicine, University of Washington, Seattle, Washington, United States of America.
  • Pavlakis GN; Department of Global Health, University of Washington, Seattle, Washington, United States of America.
  • Felber BK; Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS Pathog ; 17(9): e1009701, 2021 09.
Article in English | MEDLINE | ID: covidwho-1701737
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, DNA / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / Macaca mulatta Type of study: Cohort study / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Animals Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009701

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, DNA / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / Macaca mulatta Type of study: Cohort study / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Animals Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009701