Two Novel Adenovirus Vectors Mediated Differential Antibody Responses via Interferon-α and Natural Killer Cells.
Two Novel Adenovirus Vectors Mediated Differential Antibody Responses via Interferon-α and Natural Killer Cells.
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DOI：
10.1128/spectrum.00880-23
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发表时间：
2023-08-17
影响因子：
3.7
通讯作者：
Li, Tingting
中科院分区：
文献类型：
--
作者：
Zou, Peng;Zhang, Panli;Deng, Qitao;Wang, Cong;Luo, Shengxue;Zhang, Ling;Li, Chengyao;Li, Tingting
关键词：
重组腺病毒载体已广泛应用于疫苗开发。为了克服人群中预先存在的人类 5 型腺病毒 (Ad5) 的免疫力，已经产生了一系列黑猩猩或稀有人类腺病毒载体。然而，这些新型腺病毒载体介导宿主体内不同的免疫反应。在本研究中，我们探索了通过我们之前开发的两种新型猿猴腺病毒 23 型 (Sad23L) 和人腺病毒 49 型 (Ad49L) 以及 Ad5 载体的 COVID-19 疫苗免疫的小鼠对 SARS-CoV-2 S 蛋白的差异抗体反应的免疫机制。 Sad23L-nCoV-S和Ad5-nCoV-S疫苗在野生型和IFN-α/β受体缺陷（IFNAR−/−）C57小鼠中诱导低水平的干扰素-α（IFN-α）和高水平的抗原特异性抗体反应，而Ad49L-nCoV-S疫苗在C57小鼠中诱导高水平的IFN-α和低抗体反应，但在IFNAR−/−小鼠中诱导高抗体反应。此外，在用 Ad49L-nCoV-S 疫苗免疫的自然杀伤 (NK) 细胞阻断的 C57 小鼠中检测到高抗体反应，但在滤泡辅助 T (TFH) 细胞阻断的 C57 小鼠中检测到低抗体反应。这些结果表明，Ad49L载体疫苗刺激IFN-α分泌以激活NK细胞，然后减少TFH细胞、生成中心（GC）B细胞和浆细胞的数量，随后减少抗原特异性抗体的产生。可以根据针对特定疾病的体液或细胞或两者免疫保护的需要，选择不同的新型腺病毒载体用于疫苗开发。重要性新型腺病毒载体是疫苗开发的重要抗原递送平台。了解不同腺病毒载体之间的免疫多样性对于设计针对目标疾病的适当疫苗至关重要。在这项研究中，我们描述了 Sad23L 和 Ad49L 载体疫苗在小鼠中提高同样高的特异性 T 细胞反应但不同水平的特异性抗体反应的免疫机制。我们发现Ad49L载体疫苗启动高IFN-α并激活NK细胞，通过下调CD4+ TFH细胞的数量来抑制抗体反应，从而导致GC B细胞和浆细胞的减少。
Recombinant adenovirus vectors have been widely used in vaccine development. To overcome the preexisting immunity of human adenovirus type 5 (Ad5) in populations, a range of chimpanzee or rare human adenovirus vectors have been generated. However, these novel adenovirus vectors mediate the diverse immune responses in the hosts. In this study, we explored the immune mechanism of differential antibody responses to SARS-CoV-2 S protein in mice immunized by our previously developed two novel simian adenovirus type 23 (Sad23L) and human adenovirus type 49 (Ad49L), and Ad5 vectored COVID-19 vaccines. Sad23L-nCoV-S and Ad5-nCoV-S vaccines induced the low level of interferon-α (IFN-α) and the high level of antigen-specific antibody responses in wild-type and IFN-α/β receptor defective (IFNAR−/−) C57 mice, while Ad49L-nCoV-S vaccine induced the high IFN-α and low antibody responses in C57 mice but the high antibody response in IFNAR−/− mice. In addition, the high antibody response was detected in natural killer (NK) cells-blocked but the low in follicular helper T (TFH) cells -blocked C57 mice immunized with Ad49L-nCoV-S vaccine. These results showed that Ad49L vectored vaccine stimulated IFN-α secretion to activate NK cells, and then reduced the number of TFH cells, generation center (GC) B cells and plasma cells, and subsequently reduced antigen-specific antibody production. The different novel adenovirus vectors could be selected for vaccine development according to the need for either humoral or cellular or both immune protections against a particular disease. IMPORTANCE Novel adenovirus vectors are an important antigen delivery platform for vaccine development. Understanding the immune diversity between different adenoviral vectors is critical to design the proper vaccine against an aim disease. In this study, we described the immune mechanism of Sad23L and Ad49L vectored vaccines for raising the equally high specific T cell response but the different level of specific antibody responses in mice. We found that Ad49L-vectored vaccine initiated the high IFN-α and activated NK cells to inhibit antibody response via downregulating the number of CD4+ TFH cells leading to the decline of GC B cells and plasma cells.
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影响因子：
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影响因子：
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