Intradermal-delivered DNA vaccine induces durable immunity mediating a reduction in viral load in a rhesus macaque SARS-CoV-2 challenge model

皮内注射的DNA疫苗可诱导持久免疫力,从而降低恒河猴SARS-CoV-2攻击模型中的病毒载量。

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作者:Ami Patel ,Jewell N Walters ,Emma L Reuschel ,Katherine Schultheis ,Elizabeth Parzych ,Ebony N Gary ,Igor Maricic ,Mansi Purwar ,Zeena Eblimit ,Susanne N Walker ,Diana Guimet ,Pratik Bhojnagarwala ,Opeyemi S Adeniji ,Arthur Doan ,Ziyang Xu ,Dustin Elwood ,Sophia M Reeder ,Laurent Pessaint ,Kevin Y Kim ,Anthony Cook ,Neethu Chokkalingam ,Brad Finneyfrock ,Edgar Tello-Ruiz ,Alan Dodson ,Jihae Choi ,Alison Generotti ,John Harrison ,Nicholas J Tursi ,Viviane M Andrade ,Yaya Dia ,Faraz I Zaidi ,Hanne Andersen ,Mohamed Abdel-Mohsen ,Mark G Lewis ,Kar Muthumani ,J Joseph Kim ,Daniel W Kulp ,Laurent M Humeau ,Stephanie J Ramos ,Trevor R F Smith ,David B Weiner ,Kate E Broderick

Abstract

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health and social and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (i.d.)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system, which are likely important for providing durable protection against COVID-19 disease. Keywords: COVID-19; ID DNA vaccine; SARS-CoV-2; challenge; coronavirus; electroporation; infectious disease; macaque; protection.

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