Hilfenhaus J, De Clercq E, Köhler R, Geursen R, Seiler F
Antiviral Res. 1987 May;7(4):227-35. doi: 10.1016/0166-3542(87)90031-3.
Suboptimal dosage regimens of antivirals (acyclovir or bromovinyldeoxyuridine) and human immunoglobulin have been combined in the treatment of hairless mice infected with herpes simplex virus type 1. The aim of this study was to establish how late after infection human immunoglobulin could be given to still be effective and for how long would the protective effect last. The combination of acyclovir or bromovinyldeoxyuridine with passive immunization proved additive or even synergistic depending on the time of immunoglobulin administration and the observation period after infection. When the survival rate of the mice was followed for up to 20 days postinfection, synergistic action seemed to occur with immunoglobulin given as late as 2 or 3 days after infection. When the mice were followed for up to 100 days after infection, however, it turned out that only the immunoglobulin given 4 h after infection led to a synergistic effect with the antivirals. Most of the mice subjected to combined treatment, in contrast to mice treated with the antivirals only, did not develop anti-HSV antibodies. This lack of a specific humoral immune response possibly reflects the rapid inhibition of virus replication early after challenge by the combined treatment, thus preventing the production of a sufficient amount of viral antigen in the body needed for a measurable antibody induction.
抗病毒药物（阿昔洛韦或溴乙烯脱氧尿苷）与人类免疫球蛋白的次优剂量方案已被联合用于治疗感染1型单纯疱疹病毒的无毛小鼠。本研究的目的是确定感染后多久给予人类免疫球蛋白仍有效，以及保护作用能持续多长时间。根据免疫球蛋白给药时间和感染后的观察期，阿昔洛韦或溴乙烯脱氧尿苷与被动免疫的联合作用证明是相加的，甚至是协同的。当在感染后长达20天跟踪小鼠的存活率时，在感染后2或3天给予免疫球蛋白似乎会出现协同作用。然而，当在感染后长达100天跟踪小鼠时，结果发现只有在感染后4小时给予免疫球蛋白才会与抗病毒药物产生协同作用。与仅用抗病毒药物治疗的小鼠相比，大多数接受联合治疗的小鼠没有产生抗HSV抗体。缺乏特异性体液免疫反应可能反映了联合治疗在攻击后早期对病毒复制的快速抑制，从而阻止了体内产生可诱导可测量抗体所需的足够量的病毒抗原。
