2003 Fiscal Year Final Research Report Summary
| Project/Area Number |
14406020
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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 | 海外学術 |
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| Research Field |
内科学一般
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| Research Institution | Oita University |
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Principal Investigator |
YAMASHIRO Tetsu Oita University, Institute of Scientific Research, Associate Professor, 医学部・総合科学研究支援センター, 助教授 (00244335)
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| Co-Investigator(Kenkyū-buntansha) |
SONODA Yoshiko Oita University, Institute of Scientific Research, Assistant Professor, 医学部・総合科学研究支援センター, 助手 (80253780)
MAKINO Yoshihiro Oita University, Department of Infectious Diseases, Professor, 医学部, 教授 (60039930)
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| Project Period (FY) |
2002 – 2003
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| Keywords | combinatorial science / phage display / dengue infection / tropical medicine / infectious diseases / humanized antibody / Antibody engineering / antibody therapy |
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| Research Abstract |
The sero-prevalence of dengue virus (DEN)-specific IgG was determined among 1008 adults and among 201 children younger than 10 years old, in Santo Domingo Dominican Republic Most adults (98%, 987/1008) and 56% (113/201) of children were positive for DEN-specific IgG. Among children, the prevalence of DEN-specific IgG increased with age, that is, 1 to 2 yr, 0--5%, 3 to 6 yr, 25 --65%, and 【greater than or equal】 7 yr, 76 --92%. Fifty percent of the prevalence shown in <1 group was probably due to maternal antibody transfer. Neutralization tests of adult samples indicate that DEN infections with different serotypes have occurred sequentially or simultaneously among the inhabitants of Santo Domingo. Fab monoclonal antibodies to DEN4 were recovered from mRNA from immune higher primate. Two Fabs neutralized DEN4 efficiently with a titer of 0.24-0.48 micro g/mL by PRNT. One of the Fab was converted to full-length IgG1 by combining it with human sequences. The humanized IgG1 neutralized DEN4 strains from different geographical origins at a similar PRNT50 titer. A human Fab library was constructed from PBL of volunteers who had recovered from severe DEN infection. The phage library was panned several times with DEN1, DEN2, DEN3, and DEN4 virions, and recombinant DEN4 NS1 protein, and Japanese encephalitis virus virion.
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