Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant.

Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant.
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热灭活的修饰的安卡拉牛痘病毒作为疫苗佐剂增强Th1细胞和体液免疫。

DOI:
10.1038/s41541-022-00542-5
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发表时间:
2022-10-19
期刊:
影响因子:
9.2
通讯作者:
--
中科院分区:
医学1区
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--
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基于蛋白质或肽的亚单位疫苗引起了人们的兴奋,并重新燃起了对抗人类癌症或 COVID-19 爆发的兴趣。亚单位疫苗应用的一个主要问题是蛋白质或肽诱导的免疫反应较弱。开发新型有效的疫苗佐剂对于亚单位疫苗的成功至关重要。在这里,我们探讨了热灭活 MVA (heat-iMVA) 作为疫苗佐剂的潜力。当与基于蛋白质或肽的免疫原结合时,Heat-iMVA 可显着增强 T 细胞反应和抗体反应,主要针对 Th1 免疫反应。 Heat-iMVA 的佐剂作用比活 MVA 更强,并且依赖于 cGAS/STING 介导的胞质 DNA 传感途径。在基于肿瘤新抗原肽疫苗的治疗性疫苗接种模型中,Heat-iMVA 显着延长了存活时间并延缓了肿瘤生长。当与 SARS-CoV-2 刺突蛋白结合时,Heat-iMVA 诱导产生更强大的刺突特异性抗体和更有效的中和抗体。我们的结果支持 Heat-iMVA 可以开发为一种安全有效的疫苗佐剂,用于抗癌症或 SARS-CoV-2 的亚单位疫苗。
Protein or peptide-based subunit vaccines have generated excitement and renewed interest in combating human cancer or COVID-19 outbreak. One major concern for subunit vaccine application is the weak immune responses induced by protein or peptides. Developing novel and effective vaccine adjuvants are critical for the success of subunit vaccines. Here we explored the potential of heat-inactivated MVA (heat-iMVA) as a vaccine adjuvant. Heat-iMVA dramatically enhances T cell responses and antibodies responses, mainly toward Th1 immune responses when combined with protein or peptide-based immunogen. The adjuvant effect of Heat-iMVA is stronger than live MVA and is dependent on the cGAS/STING-mediated cytosolic DNA-sensing pathway. In a therapeutic vaccination model based on tumor neoantigen peptide vaccine, Heat-iMVA significantly extended the survival and delayed tumor growth. When combined with SARS-CoV-2 spike protein, Heat-iMVA induced more robust spike-specific antibody production and more potent neutralization antibodies. Our results support that Heat-iMVA can be developed as a safe and potent vaccine adjuvant for subunit vaccines against cancer or SARS-CoV-2.
静脉注射纳米颗粒疫苗接种产生茎状的TCF1(+)新抗原特异性CD8(+)T细胞。
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