Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
Pan Genome Systems, Madison, WI 53719, USA.
Viruses. 2022 Jun 10;14(6):1262. doi: 10.3390/v14061262.
Antibody measurements are primarily used to evaluate experimental and approved COVID-19 vaccines, which is unilateral considering our immune responses' complex nature. Previously, we showed that nanoparticle plasmid DNA adjuvant system, QAC, and MVA based vaccines were immunogenic against SARS-CoV-2. Here, we report on the protective efficacy of systemic humoral and mucosal cell-mediated immune responses in transgenic mice models against SARS-CoV-2 following nanoparticle immunization. Parenteral, intramuscular administration of QAC-based plasmid DNA vaccine-encoding SARS-CoV-2 S and N led to the induction of significant serum neutralizing humoral responses, which reduced viral burden in the lungs and prevented viral dissemination to the brain. In contrast, the mucosal, intranasal administration of a heterologous vaccine elicited significant mucosal cell-mediated immune responses in the lungs that limited lung viral replication. The presented results demonstrate that serum neutralizing humoral and local lung T-cell immune responses are critical for the control of SARS-CoV-2 replication.
抗体检测主要用于评估实验性和已批准的 COVID-19 疫苗，这是片面的，因为我们的免疫反应具有复杂的性质。此前，我们已经表明，基于纳米颗粒质粒 DNA 佐剂系统、QAC 和 MVA 的疫苗对 SARS-CoV-2 具有免疫原性。在这里，我们报告了纳米颗粒免疫后针对 SARS-CoV-2，在转基因小鼠模型中系统体液和黏膜细胞介导的免疫应答的保护效力。基于 QAC 的质粒 DNA 疫苗编码 SARS-CoV-2 S 和 N 的肌内或肌内给药导致显著的血清中和体液免疫应答，从而降低肺部的病毒负担并防止病毒传播到大脑。相比之下，异源疫苗的黏膜、鼻内给药在肺部引发了显著的黏膜细胞介导的免疫应答，从而限制了肺部的病毒复制。所呈现的结果表明，血清中和体液和肺部局部 T 细胞免疫应答对于控制 SARS-CoV-2 复制至关重要。
