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在小鼠模型中,与已获许可的亚单位疫苗相比,水痘带状疱疹病毒mRNA候选疫苗诱导出更强的细胞免疫以及相当的体液免疫和Fc介导的免疫。

Varicella zoster virus mRNA vaccine candidate induced superior cellular immunity and comparable humoral and Fc-mediated immunity compared to the licensed subunit vaccine in a mouse model.

作者信息

Jang Eun-Jeong, Xayaheuang Sivilay, Hwang Ji-Young, Kim Yunhwa, Lee Kyung-Min, Choi Seok-Tae, Kwak Hye Won, Nam Jae-Hwan, Kim Keunea, Yoon Boomi, Lim Jae Hyang, Seo Ho Seong, Woo Chang-Hoon, Park Hosun

机构信息

Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.

Central Research Institute, SML Biopharm, Gwangmyeong-si, Gyeonggi-do, Republic of Korea.

出版信息

Hum Vaccin Immunother. 2025 Dec;21(1):2495607. doi: 10.1080/21645515.2025.2495607. Epub 2025 May 7.

Abstract

The threat of herpes zoster (HZ) is increasing, particularly in the elderly and immunocompromised individuals. Although two platform vaccines are currently available for HZ prevention, the low effectiveness of the live attenuated varicella-zoster virus vaccine (Zostavax®), and the high reactogenicity and limited supply of the AS01 adjuvant gE subunit vaccine (Shingrix®) indicate that, the development of more effective and safe vaccines is required. Compared to conventional vaccines, mRNA vaccines offer the advantages of faster production and generally do not require adjuvants. However, no authorized mRNA vaccine is currently available for HZ. Therefore, we aimed to prepare a gE mRNA vaccine and evaluate the immunogenicity compared with the two commercial vaccines in mice. The gE mRNA vaccine elicited a robust humoral immune response, as measured by an enzyme-linked immunosorbent assay and the fluorescent antibody to membrane antigen test. The mRNA vaccine binding antibody level was comparable to that of Shingrix® and significantly higher than that of Zostavax®. In contrast, in cellular immune responses, which were evaluated by ELISpot assays and intracellular cytokine staining assay, the VZV gE mRNA vaccine induced significantly higher responses than Zostavax® and Shingrix®. In addition, the antibody-dependent cellular phagocytosis activity of the gE mRNA vaccine was comparable to that of the commercial vaccines. However, the highest antibody-dependent cellular cytotoxicity response was achieved by Shingrix®, followed by gE mRNA and then Zostavax®. Our results demonstrate that the mRNA HZ vaccine candidate elicited robust immunogenicity, especially in cellular immunity, and shows a promising potential for HZ prevention.

摘要

带状疱疹(HZ)的威胁正在增加,尤其是在老年人和免疫功能低下的个体中。尽管目前有两种平台疫苗可用于预防HZ,但减毒活水痘-带状疱疹病毒疫苗(Zostavax®)的有效性较低,以及AS01佐剂gE亚单位疫苗(Shingrix®)的高反应原性和供应有限表明,需要开发更有效和安全的疫苗。与传统疫苗相比,mRNA疫苗具有生产速度更快且通常不需要佐剂的优点。然而,目前尚无经授权的用于HZ的mRNA疫苗。因此,我们旨在制备一种gE mRNA疫苗,并在小鼠中与两种商业疫苗比较评估其免疫原性。通过酶联免疫吸附测定和膜抗原荧光抗体试验测定,gE mRNA疫苗引发了强烈的体液免疫反应。mRNA疫苗结合抗体水平与Shingrix®相当,且显著高于Zostavax®。相比之下,在通过ELISpot试验和细胞内细胞因子染色试验评估的细胞免疫反应中,VZV gE mRNA疫苗诱导的反应明显高于Zostavax®和Shingrix®。此外,gE mRNA疫苗的抗体依赖性细胞吞噬活性与商业疫苗相当。然而,抗体依赖性细胞毒性反应最高的是Shingrix®,其次是gE mRNA,然后是Zostavax®。我们的结果表明,候选mRNA HZ疫苗引发了强烈的免疫原性,尤其是在细胞免疫方面,并且在预防HZ方面显示出有前景的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f16/12064069/70f66108ffd4/KHVI_A_2495607_F0001_OC.jpg

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