Localized and Systemic Immune Responses against SARS-CoV-2 Following Mucosal Immunization.

Localized and Systemic Immune Responses against SARS-CoV-2 Following Mucosal Immunization.
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DOI:
10.3390/vaccines9020132
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发表时间:
2021-02-06
期刊:
影响因子:
7.8
通讯作者:
Talaat AM
Talaat AM
中科院分区:
医学3区
文献类型:
--
作者:
Chandrasekar SS;Phanse Y;Hildebrand RE;Hanafy M;Wu CW;Hansen CH;Osorio JE;Suresh M;Talaat AM

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SARS-CoV-2病毒在美国和世界范围内的快速传播需要开发多种疫苗来对抗新冠肺炎全球大流行。此前,我们证明了一种颗粒佐剂系统,即载Quil-A的壳聚糖纳米粒(QAC),当用于对抗禽流感冠状病毒时,可以与质粒疫苗结合起来诱导强大的免疫力。本文报道了表达SARS-CoV-2棘突蛋白(S)和核衣壳蛋白(N)抗原的黏膜同源质粒和表达SARS-CoV-2棘突(S)和核衣壳(N)抗原的改良安卡拉痘苗的异种免疫策略。只有异种鼻腔免疫策略才能在小鼠的血清和支气管肺泡灌洗液中诱导出抗SARS-CoV-2的中和抗体,这可能是一种保护性疫苗。相同的PRIME/BOOST策略在免疫小鼠的肺和脾中诱导了1型和17型T细胞反应以及表达多种1型细胞因子(如干扰素-γ、肿瘤坏死因子α、IL-2)的多功能T细胞。相反,质粒同源疫苗策略导致了局部分泌干扰素-γ的单一和多功能T细胞的诱导。这项研究的结果支持了QAC-纳米疫苗有可能引发针对呼吸道冠状病毒的显著粘膜免疫反应。
The rapid transmission of SARS-CoV-2 in the USA and worldwide necessitates the development of multiple vaccines to combat the COVID-19 global pandemic. Previously, we showed that a particulate adjuvant system, quil-A-loaded chitosan (QAC) nanoparticles, can elicit robust immunity combined with plasmid vaccines when used against avian coronavirus. Here, we report on the immune responses elicited by mucosal homologous plasmid and a heterologous immunization strategy using a plasmid vaccine and a Modified Vaccinia Ankara (MVA) expressing SARS-CoV-2 spike (S) and nucleocapsid (N) antigens. Only the heterologous intranasal immunization strategy elicited neutralizing antibodies against SARS-CoV-2 in serum and bronchoalveolar lavage of mice, suggesting a protective vaccine. The same prime/boost strategy led to the induction of type 1 and type 17 T-cell responses and polyfunctional T-cells expressing multiple type 1 cytokines (e.g., IFN-γ, TNFα, IL-2) in the lungs and spleens of vaccinated mice. In contrast, the plasmid homologous vaccine strategy led to the induction of local mono and polyfunctional T-cells secreting IFN-γ. Outcomes of this study support the potential of QAC-nano vaccines to elicit significant mucosal immune responses against respiratory coronaviruses.
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