Prevention of HTLV-I infection by recombinant vaccinia virus

在第一个实验中，用重组痘苗病毒WR-SFB5env和对照病毒HA-WR免疫，每组3只。重组痘苗病毒WR-SFB5env携带人T淋巴细胞淋巴病毒I型(HTLV-1)env基因的血凝素基因位于WR株的血凝素基因位点。所有6只兔子均呈抗痘苗病毒抗体反应。WR-SFB5env在3只兔体内均能诱导产生抗HTLV-I包膜抗体，但不能产生水疱性口炎病毒(HTLV-I)假型中和抗体。10周后，这些动物接受从感染HTLV-I的兔身上输血的挑战。免疫3只兔中有2只感染HTLV-I，3只对照兔全部感染HTLV-I，血清学检测和聚合酶链式反应检测HTLV-I前病毒序列。在首次攻击后12周再次攻击的兔子感染了HTLV-I。鉴于已证实的预防效果…由于对HTLV-I的被动免疫时间较长，我们的疫苗试验失败了，因为WR-SFB5env不能在免疫的动物中诱导针对HTLV-I的中和抗体。在第二个实验中，从HTLV-I阳性健康人制备的高免疫球蛋白H-Ig G在日本猕猴(Macaca Fuscata)身上检测了其对HTLV-I感染的预防作用。用H-Ig G免疫的4只猕猴和用病毒感染的Ra-1细胞攻击的4只猕猴均获得保护，而2只给予正常Ig G的对照组在Ra-1攻击后均被感染。H-Ig G在猕猴体内的半衰期约为2周，攻击前血清中和抗体效价为1：60或更高为保护性抗体。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。较少

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