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Multivalent DNA vaccine protects against genital herpes by T-cell immune induction in vaginal mucosa.
Antiviral Research ( IF 4.5 ) Pub Date : 2020-02-26 , DOI: 10.1016/j.antiviral.2020.104755
Hyeon Cheol Kim 1 , Dong Sun Oh 1 , Jang Hyun Park 1 , Hyun-Jin Kim 1 , Yong Bok Seo 2 , Hye Jee Yoo 3 , Hye Seon Jang 3 , Jua Shin 2 , Chae Won Kim 1 , Myeong Seung Kwon 4 , Hyun-Tak Jin 5 , Sung Ki Lee 4 , Ji Eun Oh 1 , Heung Kyu Lee 6
Affiliation  

Genital herpes is one of the most common sexually transmitted infections (STIs), and it is mainly caused by the neurotropic herpes simplex virus (HSV-2). Not only does this infection cause ulcers, but HSV-2 can also stay in a latent state in the nervous system of the host throughout their lifespan. As a result, many people do not know that they harbor this infection. Moreover, HSV-2 serves as a major risk factor for human immunodeficiency virus (HIV) infection and can be transmitted to the fetus. Despite the high risk of infection and adverse effects, attempts at development of an effective vaccine for HSV-2 have not yet been successful. In this study, we developed a DNA vaccine for HSV-2 (SL-V20). This multivalent DNA vaccine effectively reduced the pathological symptoms of infection and induced efficient elimination of the virus in a mouse model. Intramuscular injection of SL-V20 led to induction of an HSV-2-specific T-cell response in the vagina, the major infection site, and in draining lymph organs. Dendritic cells (DCs), especially basic leucine zipper ATF-like transcription factor 3 (Baft3)+ DCs and partially interferon regulatory factor 4 (Irf4)+ DCs, were involved in this T-cell-mediated protective response, while B cells were dispensable for these prophylactic effects. This study demonstrates that SL-V20 offers a novel and effective vaccine against vaginal HSV-2 infection and may be applicable to patients, pending validation in clinical studies.

中文翻译:

多价DNA疫苗可通过阴道粘膜中的T细胞免疫诱导保护生殖器疱疹。

生殖器疱疹是最常见的性传播感染(STIs)之一,主要由神经性单纯疱疹病毒(HSV-2)引起。这种感染不仅会导致溃疡,而且HSV-2还可在宿主的整个生命周期中保持潜伏状态。结果,许多人不知道他们感染了这种病毒。此外,HSV-2是人类免疫缺陷病毒(HIV)感染的主要危险因素,可以传播给胎儿。尽管有很高的感染风险和不良反应,但开发针对HSV-2的有效疫苗的尝试尚未成功。在这项研究中,我们开发了HSV-2(SL-V20)的DNA疫苗。这种多价DNA疫苗可有效减轻感染的病理症状,并在小鼠模型中有效消除病毒。肌肉内注射SL-V20可在阴道,主要感染部位和引流淋巴器官中诱导HSV-2特异性T细胞应答。树突状细胞(DC),特别是碱性亮氨酸拉链ATF样转录因子3(Baft3)+ DC和部分干扰素调节因子4(Irf4)+ DC,参与了这种T细胞介导的保护性反应,而B细胞则是可有可无的这些预防作用。这项研究表明SL-V20提供了一种针对阴道HSV-2感染的新型有效疫苗,可能在临床研究中有待验证的情况下,可应用于患者。尤其是碱性亮氨酸拉链ATF样转录因子3(Baft3)+ DC和部分干扰素调节因子4(Irf4)+ DC参与了这种T细胞介导的保护性反应,而B细胞则可起到这些预防作用。这项研究表明SL-V20提供了一种针对阴道HSV-2感染的新型有效疫苗,可能在临床研究中有待验证的情况下可应用于患者。尤其是碱性亮氨酸拉链ATF样转录因子3(Baft3)+ DC和部分干扰素调节因子4(Irf4)+ DC参与了这种T细胞介导的保护性反应,而B细胞则可起到这些预防作用。这项研究表明SL-V20提供了一种针对阴道HSV-2感染的新型有效疫苗,可能在临床研究中有待验证的情况下可应用于患者。
更新日期:2020-02-26
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