| Project/Area Number |
13470345
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | UNIVERSITY OF TSUKUBA |
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Principal Investigator |
YOSHIKAWA Hiroyuki UNIVERSITY OF TSUKUBA, DEPARTMENT OF OB/GYN, PROFESSOR, 臨床医学系, 教授 (40158415)
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| Co-Investigator(Kenkyū-buntansha) |
YASUGI Toshiharu UNIVERSITY OF TOKYO, DEPARTMENT OF OB/GYN, LECTURER, 医学部, 助手 (20251267)
OKI Akinori UNIVERSITY OF TSUKUBA, DEPARTMENT OF OB/GYN, ASSISTANT PROFESSOR, 臨床医学系, 講師 (60334067)
TSUNODA Hajime UNIVERSITY OF TSUKUBA, DEPARTMENT OF OB/GYN, ASSOCIATE PROFESSOR, 臨床医学系, 助教授 (60197754)
KAWANA Takashi UNIVERSITY OF TOKYO, DEPARTMENT OF OB/GYN, LECTURER, 医学部, 助手 (60311627)
市川 喜仁 筑波大学, 臨床医学系, 講師 (30302425)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2002: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2001: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | HPV / Cervical Cancer / Vaccine / VLP / HLA / Phase I / II trial / CIN / E6 / 子宮頚がん / VLP抗体 / 子宮頸癌 / variants / L2 |
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| Research Abstract |
1.Amino acid (aa) 108-120 of L2 protein of HPV16 contains a cross-neutralization epitope against genital HPV. We designed a placebo-controlled trial in healthy adults to evaluate the safety and immunogenicity of a synthetic peptide consisting of the aa 108-120 of HPV 16 L2(L2-108/120) region. A total of 13 volunteers were given nasal inoculations with 0.1 (n=5) or 0.5mg (n=5) doses of the peptides or placebo (n=3) without adjuvant at weeks 0, 4, and 12. Sera were collected before inoculation and at 6, 16 and 36 weeks. The inoculation generated anti-L2 antibodies binding to both HPV16 and 52 L1/L2-capsids in four of the five recipients in the 0.5mg group. Sera of the four recipients showed neutralizing activities against HPV16 and 52. This study suggests the L2-108/120 peptide is tolerable in humans and has the potential as a broad-spectrum prophylactic vaccine against genital HPV
2.To investigate the association between E6 variants and HLA polymorphism within a Japanese population, 55 women with HPV 16-positive cervical cancer were analyzed for E6 sequence variation and its relationship to HLA class II alleles. Compared with local controls (n=138) and published controls (n=916), DRB1*1501 and DQB1*0602 frequencies were significantly increased among patients with HPV 16 E6 prototype (n=11). Additionally, DRB1*1502 was positively associated with a particular E6 variant designated D25E (n=25), although we could not find a significant association between HLA class II alleles and L83V variant (n=16). Our doservations suggest that a specific match between E6variant proteins and HLA types may contribute to HPV16-related cervical carcinogenesis
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