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皮内递送 DNA 疫苗可诱导持久免疫，介导恒河猴 SARS-CoV-2 挑战模型中病毒载量的降低。

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

机构信息

Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.

Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA.

出版信息

Cell Rep Med. 2021 Oct 19;2(10):100420. doi: 10.1016/j.xcrm.2021.100420. Epub 2021 Sep 28.

DOI:10.1016/j.xcrm.2021.100420
PMID:34604818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8479327/
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.

摘要

新型冠状病毒病（COVID-19）是由 SARS-CoV-2 病毒引起的，对全球公共卫生和社会经济基础设施造成了巨大影响。在这里，我们评估了正在临床试验中评估的皮下（i.d.）递送 SARS-CoV-2 刺突 DNA 疫苗 INO-4800 在恒河猴中的免疫原性和记忆保护性功效。INO-4800 疫苗接种诱导 T 细胞反应，并诱导具有 ADCP 和 ADCD 活性的刺突抗原和 RBD 结合抗体。来自动物的血清中和了 D614 和 G614 SARS-CoV-2 假型病毒。接种疫苗几个月后，动物受到 SARS-CoV-2 的挑战，导致快速回忆起抗 SARS-CoV-2 刺突蛋白 T 细胞和中和抗体反应。这些反应与肺部的病毒载量较低有关。这些研究支持 INO-4800 对诱导体液和细胞适应性免疫系统的免疫影响，这对于提供针对 COVID-19 疾病的持久保护可能很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/4afda75dfd41/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/f80460c30cf8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/67070c11549e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/83a5ff20657e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/3178a511a6f1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/4afda75dfd41/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/f80460c30cf8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/67070c11549e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/83a5ff20657e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/3178a511a6f1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb7c/8561234/4afda75dfd41/gr4.jpg

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[2]
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[3]
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[4]
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PLoS Pathog. 2024-4

[5]
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[6]
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[7]
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[8]
Humoral immunogenicity of a Coronavirus Disease 2019 (COVID-19) DNA vaccine in rhesus macaques (Macaca mulatta) delivered using needle-free jet injection.

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[9]
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[10]
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本文引用的文献

[1]
INO-4800 DNA vaccine induces neutralizing antibodies and T cell activity against global SARS-CoV-2 variants.

NPJ Vaccines. 2021-10-14

[2]
Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8 T Cells during Convalescence.

J Immunol. 2021-9-1

[3]
One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model.

Vaccine. 2021-8-9

[4]
Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus.

JCI Insight. 2021-5-24

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BNT162b vaccines protect rhesus macaques from SARS-CoV-2.

Nature. 2021-4

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SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice.

Nat Commun. 2021-1-14

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Science. 2021-2-5

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MMWR Morb Mortal Wkly Rep. 2021-1-1

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MMWR Morb Mortal Wkly Rep. 2020-12-11

[10]
Correlates of protection against SARS-CoV-2 in rhesus macaques.

Nature. 2021-2

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