Silke Heilingloh Christiane, Lull Christopher, Kleiser Elissa, Alt Mira, Schipper Leonie, Witzke Oliver, Trilling Mirko, Eis-Hübinger Anna-Maria, Dittmer Ulf, Krawczyk Adalbert
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany.
Biopharmaceuticals QC Services, Virology & Contamination Detection, Boehringer Ingelheim, D-55216 Biberach, Germany.
Vaccines (Basel). 2020 Aug 27;8(3):478. doi: 10.3390/vaccines8030478.
Infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are a global health burden. Besides painful oral or genital lesions in otherwise healthy subjects, both viruses can cause devastating morbidity and mortality in immune-compromised and immune-immature individuals. The latter are particularly susceptible to a disseminated, life-threatening disease. Neutralizing antibodies (NAb) constitute a correlate of protection from disease, and are promising candidates for the prophylactic or therapeutic treatment of severe HSV infections. However, a clinical vaccine trial suggested that HSV-2 might be more resistant to NAbs than HSV-1. In the present study, we investigated the antiviral efficacy of the well-characterized humanized monoclonal antibody (mAb) hu2c against HSV-2, in a NOD/SCID immunodeficiency mouse model. Despite the fact that hu2c recognizes a fully conserved epitope and binds HSV-1 and HSV-2 glycoprotein B with equal affinity, it was much less effective against HSV-2 in vitro and in NOD/SCID mice. Although intravenous antibody treatment prolonged the survival of HSV-2-infected mice, complete protection from death was not achieved. Our data demonstrate that HSV-2 is more resistant to NAbs than HSV-1, even if the same antibody and antigen are concerned, making the development of a vaccine or therapeutic antibodies more challenging.
1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）感染是一项全球性的健康负担。除了在其他方面健康的个体中引起口腔或生殖器疼痛性损伤外，这两种病毒在免疫功能低下和免疫未成熟个体中均可导致严重发病和死亡。后者尤其易患播散性、危及生命的疾病。中和抗体（NAb）是预防疾病的一个相关因素，是严重HSV感染预防性或治疗性治疗的有前景的候选药物。然而，一项临床疫苗试验表明，HSV-2可能比HSV-1对中和抗体更具抗性。在本研究中，我们在NOD/SCID免疫缺陷小鼠模型中研究了特性明确的人源化单克隆抗体（mAb）hu2c对HSV-2的抗病毒效果。尽管hu2c识别一个完全保守的表位并以同等亲和力结合HSV-1和HSV-2糖蛋白B，但它在体外和NOD/SCID小鼠中对HSV-2的效果要差得多。虽然静脉内抗体治疗延长了HSV-2感染小鼠的存活时间，但并未实现完全保护使其免于死亡。我们的数据表明，即使涉及相同的抗体和抗原，HSV-2比HSV-1对中和抗体更具抗性，这使得疫苗或治疗性抗体的研发更具挑战性。
