Prevention of HTLV-I infection by recombinant vaccinia virus

在第一个实验中，将两组3只兔分别接种重组痘苗病毒（WR- sfb5env）和缺乏功能性血凝素基因的对照痘苗病毒（HA-WR）。重组痘苗病毒（WR- sfb5env）在WR毒株的血凝素基因位点携带HTLV-1基因。6只兔均产生抗牛痘病毒抗体。WR-SFB5env在3只家兔中均能诱导出HTLV-I型的env抗体，但未诱导出HTLV-I型假中和抗体。10周后，这些动物接受htlv - 1感染兔子的血液输血。经血清转化和聚合酶链反应检测HTLV-I原序列，3只接种兔中的2只和3只对照兔均感染HTLV-I。第一次攻毒后12周再次攻毒，未受第一次攻毒保护的家兔感染htlv - 1。由于WR-SFB5env不能在免疫动物体内诱导抗HTLV-I的中和抗体，因此我们的疫苗试验失败了。细胞介导的免疫（如抗体依赖性细胞毒性）是否参与了1只接种疫苗兔的暂时保护，还有待研究。第二项实验采用日本猕猴（Macaca fuscata）血清HTLV-I阳性健康人制备的高免疫球蛋白H-IgG进行预防HTLV-I感染的试验。4只免疫了H-IgG并被病毒感染的Ra-1细胞攻击的猕猴均被保护，而2只给予正常IgG的对照在Ra-1攻击后均被感染。H-IgG在猕猴体内的半衰期约为2周，攻毒前血清中和抗体滴度为1:60或更高具有保护作用。这些发现表明，在某些临床情况下，被动抗体预防HTLV-I感染是可能的。少

In the first experiment, two groups of 3 rabbits each were immunized with either recombinant vaccinia virus, WR-SFB5env, carrying the human T-cell lymphotropic virus type I (HTLV-1) env gene at the site of the hemagglutinin gene of the WR strain, or control vaccinia virus, HA-WR,lacking the functional hemagglutinin gene. All 6 rabbits responded with anti-vaccinia virus antibodies. WR-SFB5env elicited anti-HTLV-I env antibodies but no vesicular stomatitis virus (HTLV-I) pseudotype neutralizing antibodies in all 3 rabbits. After 10 weeks, the animals were challenged by transfusion of blood from an HTLV-I-infected rabbit. Two of the 3 vaccinated rabbits and all 3 control rabbits became infected with HTLV-I,as indicated by seroconversion and detection of HTLV-I proviral sequences by polymerase chain reaction. The rabbit that had been protected from initial challenge became infected with HTLV-I by rechallenge given 12 weeks after the first challenge. In view of the proven prophylactic effec … More t of passive immunization against HTLV-I,our vaccine trial failed because WR-SFB5env was incapable of inducing neutralizing antibodies against HTLV-I in the immunized animals. It remains to be studied whether cell-mediated immunity such as antibody-dependent cellular cytotoxicity was involved in the temporary protection of 1 vaccinated rabbit.In the second experiment, hyperimmune globulin, H-IgG,prepared from healthy persons seropositive for HTLV-I was tested for its prophylactic effect against HTLV-I infection in Japanese macaques (Macaca fuscata). All 4 macaques immunized with H-IgG and challenged with virus-infected Ra-1 cells wereprotected, whereas 2 controls given normal IgG were both infected after Ra-1 challenge. The half-life of H-IgG was about 2 weeks in macaques and the serum neutralizing antibody titer of 1 : 60 or higher before challenge appeared to be protective. These findings indicate that passive antibody prophylaxis against HTLV-I infection may be possible in certain clinical situations. Less