Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs
Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs
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DOI：
10.1016/j.vaccine.2008.05.022
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发表时间：
2008-07-29
期刊：
影响因子：
5.5
通讯作者：
Cohen, Jeffrey I.
中科院分区：
文献类型：
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作者：
Hoshino, Yo;Pesnicak, Lesley;Cohen, Jeffrey I.
复制缺陷型单纯疱疹病毒 (HSV)-2 疫苗 dl5-29 删除了两个必需的早期基因 UL5 和 UL29，对小鼠和豚鼠具有高度免疫原性和保护性。在之前的一项研究中，HSV-2 dl5-29 的一种衍生物（称为 dl5-29-41L）在 UL41（编码病毒体宿主关闭蛋白）中进行了额外的删除，与 dl5-29 相比，它在小鼠中具有更强的免疫原性和对野生型 HSV-2 攻击的保护性。为了确定UL41的缺失是否提高了dl5-29在保护豚鼠免受HSV-2侵害方面的功效，用dl5-29、dl5-29-41L或PBS对动物进行免疫。来自dl5-29和dl5-29-41L受体的几何平均中和抗体滴度是可比较的(分别为10(1.97)和10(2.19)，in＝0.15)。在用野生型HSV-2进行阴道内攻击后，dl5-29-41L和dl5-29受体从阴道排出相似滴度的HSV-2。 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的致命攻击，并在动物脾脏中诱导病毒特异性CD8(+) T细胞。因此，在这些条件下，dl5-29与dl5-29-41L一样具有免疫原性和保护性。通过颅内接种健康小鼠，dl5-29 的毒性比亲代病毒低至少 250,000 倍，并且在 SCID 小鼠中没有引起疾病。 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 在免疫功能低下的动物中非常安全。由爱思唯尔有限公司出版
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, in = 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. Published by Elsevier Ltd.