1995 Fiscal Year Final Research Report Summary
Prevention of HTLV-I infection by recombinant vaccinia virus
| Project/Area Number |
06454347
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Kochi Medical School |
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Principal Investigator |
MIYOSHI Isao Kochi Medical School, Department of Medicine Professor, 医学部, 教授 (30033088)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Tetsuya Kochi Medical School, Department of Medicine Research Associate, 医学部, 助手 (30274377)
MORISHITA Nobumasa Kochi Medical School, Department of Medicine Research Associate, 医学部, 助手 (00243840)
TANAKA Yuji Kochi Medical School, Department of Medicine Research Associate, 医学部, 助手 (40243828)
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| Project Period (FY) |
1994 – 1995
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| Keywords | HTLV-I / Recombinant vaccinia virus / Vaccine / Immunoglobulin / Passive immunization / Infection prophylaxis |
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| Research Abstract |
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
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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
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