自组装TLR2激动剂促进小鼠粘膜免疫反应而不造成肺免疫病理损伤。

IF 6.9 1区 医学 Q1 IMMUNOLOGY
Zhangping Huang, Caiguanxi Deng, Lin Peng, Liru Shang, Juan Jiang, Wei Yu, Hao Yang, Jing Liu, Liwei Jiang, Teng Zuo, Ji Wang, Xiafeng Wang
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引用次数: 0

摘要

鼻腔疫苗在诱导粘膜免疫方面具有优势,特别是通过诱导二聚体IgA。然而,复杂的粘膜环境对实现最佳的免疫原性和安全性提出了挑战。本研究介绍了TLR2激动剂Diprovocim作为一种有效、安全的粘膜疫苗佐剂。我们的研究结果表明,Diprovocim自组装成适合粘膜递送的颗粒,增强淋巴结和肺部免疫细胞的抗原吞噬。在有效激活TLR2信号通路后,Diprovocim导致体内炎症细胞因子的释放减少,而没有任何组织损伤或体重减轻,突出了其安全性。在小鼠实验中,肌内和鼻内注射双嘧唑啉佐剂疫苗均可诱导高滴度的全身抗体。支气管肺泡灌洗液(BALF)中IgG和IgA抗体升高。此外,Diprovocim增强了卵清蛋白(OVA)和重组SARS-CoV-2蛋白(RFD-Fc)疫苗的免疫原性,实现了更高的CD4+和CD8+ T细胞免疫应答和对SARS-CoV-2变体的交叉保护。这些发现强调了自组装Diprovocim作为一种安全有效的粘膜疫苗佐剂的潜力,为对抗呼吸道感染提供了一种有希望的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Self-assembling TLR2 agonists promote mucosal immune responses without pulmonary immunopathologic injuries in mice.

Nasal vaccines offer advantages in eliciting mucosal immunity, particularly through the induction of dimeric IgA. However, the complex mucosal environment poses challenges in achieving optimal immunogenicity and safety. This study introduced Diprovocim, a TLR2 agonist, as an effective and safe adjuvant for mucosal vaccines. Our results demonstrated that Diprovocim self-assembled into particles of suitable size for mucosal delivery, enhancing antigen phagocytosis of immune cells in both lymph nodes and lungs. After effectively activating the TLR2 signaling pathway, Diprovocim led to a reduced release of inflammatory cytokines in vivo without any tissue damage or weight loss, highlighting its safety profile. In mice, both intramuscular and intranasal immunization with Diprovocim-adjuvanted vaccines induced high titers of systemic antibodies. Higher IgG and IgA antibodies were detected in bronchoalveolar lavage fluid (BALF). Moreover, Diprovocim enhanced the immunogenicity of ovalbumin (OVA) and recombinant SARS-CoV-2 protein (RFD-Fc) vaccines, achieving higher CD4+ and CD8+ T cell immune responses and cross-protection against SARS-CoV-2 variants. These findings highlight the potential of self-assembled Diprovocim as a safe and effective adjuvant for mucosal vaccines, offering a promising strategy for combating respiratory infections.

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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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