2004 Fiscal Year Final Research Report Summary
Prophylactic and therapeutic HPV16 vaccine using yeast expressing chimeric L1 and E7 protein.
| Project/Area Number |
15591735
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SASAGAWA Toshiyuki Kanazawa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30272975)
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| Co-Investigator(Kenkyū-buntansha) |
浜 祐子 旭硝子(株), APSPEX・事業推進部研究開発グループ, 主幹
GIGA-HAMA Yuko Asahi Glass Central Laboratory, Head of Research Group
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| Project Period (FY) |
2003 – 2004
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| Keywords | human papillomavirus type 16 (HPV16) / cervical cancer / yeast / virus-like particles (VLP) / an edible vaccine / L1-E7 chimeric protein / prophylactic vaccine / therapeutic vaccine |
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| Research Abstract |
High-risk HPV, such as HPV type 16 was the most important etiologic factor for cervical cancer, which is the secondary many cancer in women worldwide. Therefore, HPV vaccine development is one of the best ways to reduce the incidence of cervical cancer, especially in manu developing countries Koutsky et al. first demonstrate that HPV16-L1 virus-like particles (VLP), which was produced from yeast can protect HPV16-infection in women who undertook parenteral vaccination of the VLP. This suggests that VLP vaccine is highly effective against HPV16 infection. However, the parenteral VLP vaccine may be not useful in many developing countries, since it is very expensive and the injection procedure may be difficult to perform in such countries where medical stuffs are limited. We have found that an edible freeze-dried yeast vaccine containing HPV16-L1 protein enhanced with intranasal administration of a suboptimal dose of HPV16-VLP is able to induce HPV16-specific antibody responses in mice mo
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del system. In the present study, we tried to make recombinant yeast expressing L1-E7 chimeric protein in order to synthesize VLP containing oncoprotein E7. We made three different-sized L1-E7 DNA constracts which contained full-length of E7 and truncated L1 genes, and transfected them into yeast, and had got three strains of yeast expressing 57kD, 63KD, and 67KD proteins, respectively. Since we succeeded to purify VLP from the yeast producing 63KD protein, we used this strain for an edible yeast vaccine in the mice model system. If the chimeric L1-E7 VLP induced antibody against HP16, and incorporated E7 protein induced cytotoxic T lymphocytes killing HPV16-infected cell, this vaccine might be useful as prophylactic and therapeutic vaccine against HPV16 infection. In the preliminary experiment, we found that this vaccine induces HPV16 L1 antibody in the immunized mice. Now we are going to investigate this further, and to test the cytotoxic T lymphocyte response to HPV16-E7 protein in the mice Less
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