Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Serimmune, Santa Barbara, California, USA.
J Infect Dis. 2021 Nov 16;224(9):1509-1519. doi: 10.1093/infdis/jiab139.
Previous herpes simplex virus type 2 (HSV-2) vaccines have not prevented genital herpes. Concerns have been raised about the choice of antigen, the type of antibody induced by the vaccine, and whether antibody is present in the genital tract where infection occurs. We reported results of a trial of an HSV-2 replication-defective vaccine, HSV529, that induced serum neutralizing antibody responses in 78% of HSV-1-/HSV-2- vaccine recipients. Here we show that HSV-1-/HSV-2- vaccine recipients developed antibodies to epitopes of several viral proteins; however, fewer antibody epitopes were detected in vaccine recipients compared with naturally infected persons. HSV529 induced antibodies that mediated HSV-2-specific natural killer (NK) cell activation. Depletion of glycoprotein D (gD)-binding antibody from sera reduced neutralizing titers by 62% and NK cell activation by 81%. HSV-2 gD antibody was detected in cervicovaginal fluid at about one-third the level of that in serum. A vaccine that induces potent serum antibodies transported to the genital tract might reduce HSV genital infection.
先前的单纯疱疹病毒 2 型（HSV-2）疫苗未能预防生殖器疱疹。人们对疫苗选择的抗原、疫苗诱导的抗体类型以及抗体是否存在于感染发生的生殖道提出了担忧。我们报告了 HSV-2 复制缺陷型疫苗 HSV529 的试验结果，该疫苗诱导了 78%的 HSV-1-/HSV-2-疫苗接种者产生血清中和抗体反应。在这里，我们表明 HSV-1-/HSV-2-疫苗接种者产生了针对几种病毒蛋白表位的抗体；然而，与自然感染的人相比，疫苗接种者中检测到的抗体表位较少。HSV529 诱导的抗体介导了 HSV-2 特异性自然杀伤（NK）细胞的激活。从血清中耗尽糖蛋白 D（gD）结合抗体可使中和效价降低 62%，NK 细胞激活降低 81%。HSV-2 gD 抗体在宫颈阴道分泌物中的水平约为血清中的三分之一。一种能诱导大量血清抗体运输到生殖道的疫苗，可能会减少 HSV 生殖器感染。
