Hoshino Yo, Pesnicak Lesley, Dowdell Kennichi C, Lacayo Juan, Dudek Timothy, Knipe David M, Straus Stephen E, Cohen Jeffrey I
Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
Vaccine. 2008 Jul 29;26(32):4034-40. doi: 10.1016/j.vaccine.2008.05.022. Epub 2008 Jun 2.
A replication-defective herpes simplex virus (HSV)-2 vaccine, dl5-29, which is deleted for two essential early genes, UL5 and UL29, is highly immunogenic and protective in mice and guinea pigs. In a prior study, a derivative of HSV-2 dl5-29 termed dl5-29-41L, which has an additional deletion in UL41 (that encodes the virion-host shut-off protein), was more immunogenic and protective against challenge with wild-type HSV-2 in mice when compared with dl5-29. To determine if deletion of UL41 improves the efficacy of dl5-29 in protecting guinea pigs from HSV-2, animals were immunized with dl5-29, dl5-29-41L, or PBS. The geometric mean neutralizing antibody titers from the dl5-29 and dl5-29-41L recipients were comparable (10(1.97) and 10(2.19), respectively, p=0.15). After intravaginal challenge with wild-type HSV-2, the dl5-29-41L and dl5-29 recipients shed similar titers of HSV-2 from the vagina. Mean acute disease severity scores, numbers of recurrences during 3 months after infection, and latent viral loads in sacral ganglia were similar for dl5-29 and dl5-29-41L (all p values >0.05). dl5-29 and dl5-29-41L completely protected mice from lethal challenge with HSV-2 and induced virus-specific CD8(+) T cells in the spleens of the animals. Thus, dl5-29 was as immunogenic and protective as dl5-29-41L under these conditions. dl5-29 was at least 250,000-fold less virulent than parental virus by intracranial inoculation in healthy mice, and caused no disease in SCID mice. Both dl5-29-41L and dl5-29 are equally effective and immunogenic in guinea pigs, and dl5-29 is very safe in immunocompromised animals.
一种复制缺陷型单纯疱疹病毒2型（HSV-2）疫苗dl5-29，缺失了两个必需的早期基因UL5和UL29，在小鼠和豚鼠中具有高度免疫原性且具有保护作用。在先前的一项研究中，HSV-2 dl5-29的一种衍生物dl5-29-41L，在UL41（编码病毒体-宿主关闭蛋白）中有额外缺失，与dl5-29相比，在小鼠中对野生型HSV-2攻击更具免疫原性和保护作用。为了确定缺失UL41是否能提高dl5-29保护豚鼠免受HSV-2感染的效力，用dl5-29、dl5-29-41L或磷酸盐缓冲盐水（PBS）对动物进行免疫。来自dl5-29和dl5-29-41L接种动物的几何平均中和抗体滴度相当（分别为10(1.97)和10(2.19)，p = 0.15）。经野生型HSV-2阴道攻击后，dl5-29-41L和dl5-29接种动物从阴道排出的HSV-2滴度相似。dl5-29和dl5-29-41L的平均急性疾病严重程度评分、感染后3个月内的复发次数以及骶神经节中的潜伏病毒载量相似（所有p值>0.05）。dl5-29和dl5-29-41L完全保护小鼠免受HSV-2致死性攻击，并在动物脾脏中诱导出病毒特异性CD8(+) T细胞。因此，在这些条件下，dl5-29与dl5-29-41L具有相同的免疫原性和保护作用。通过在健康小鼠中颅内接种，dl5-29的毒力比亲本病毒至少低250,000倍，并且在严重联合免疫缺陷（SCID）小鼠中不引起疾病。dl5-29-41L和dl5-29在豚鼠中同样有效且具有免疫原性，并且dl5-29在免疫受损动物中非常安全。
