Aurelian L, Smith C C, Wachsman M, Paoletti E
Department of Pharmacology, University of Maryland School of Medicine, Baltimore 21201.
Rev Infect Dis. 1991 Nov-Dec;13 Suppl 11:S924-34. doi: 10.1093/clind/13.supplement_11.s924.
Vaccinia virus recombinants containing the herpes simplex virus (HSV) gene for glycoprotein D type 1 (gD-1) under control of an early (VP176) or late (VP254) vaccinia virus promoter or for HSV glycoprotein type 2 (gD-2) under control of the early promoter (VP221) were studied for their ability to induce protective immunity to HSV-2 in the guinea pig model of cutaneous recurrent disease and the mouse model of fatal disease. Titers of HSV-specific neutralizing antibody were similar in the two groups of immunized animals, but HSV-specific T cell responses were significantly higher in VP176-immunized than in VP254-immunized animals, as determined by lymphoproliferation (P less than .005) and delayed-type hypersensitivity (P less than .01) responses. The reduced responses correlated with poor expression of the gD protein and its impaired processing in infected antigen-presenting cells (splenic adherent and epidermal cells). VP176 immunization protected against primary (P much less than .001) and recurrent (P much less than .001) cutaneous HSV-2 lesions and ganglionic latency (62% protection) in the guinea pig and against zosteriform skin lesions and fatal disease in the mouse. Immunization with VP254 was not protective. In guinea pigs VP221 did not protect against primary HSV-2 cutaneous disease but did reduce the proportion of animals with recurrent disease (P less than .05). This partial protection appears to be associated with the role of type-specific antigenic determinants in gD-2 immunoregulation.
研究了痘苗病毒重组体，这些重组体含有在早期（VP176）或晚期（VP254）痘苗病毒启动子控制下的单纯疱疹病毒（HSV）糖蛋白D1型（gD-1）基因，或在早期启动子（VP221）控制下的HSV糖蛋白2型（gD-2）基因，以观察它们在皮肤复发性疾病豚鼠模型和致命疾病小鼠模型中诱导对HSV-2的保护性免疫的能力。两组免疫动物中HSV特异性中和抗体的滴度相似，但通过淋巴细胞增殖（P小于0.005）和迟发型超敏反应（P小于0.01）测定，VP176免疫的动物中HSV特异性T细胞反应明显高于VP254免疫的动物。反应降低与gD蛋白表达不佳及其在感染的抗原呈递细胞（脾黏附细胞和表皮细胞）中的加工受损有关。VP176免疫可预防豚鼠原发性（P远小于0.001）和复发性（P远小于0.001）皮肤HSV-2病变以及神经节潜伏感染（62%的保护率），并预防小鼠的带状疱疹样皮肤病变和致命疾病。用VP254免疫没有保护作用。在豚鼠中，VP221不能预防原发性HSV-2皮肤疾病，但确实降低了复发性疾病动物的比例（P小于0.05）。这种部分保护作用似乎与gD-2免疫调节中型特异性抗原决定簇的作用有关。
