| Project/Area Number |
13670463
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
MATSUSHITA Shuzo Kumamoto University, Center for AIDS Research, Professor, エイズ学研究センター, 教授 (00199788)
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | HIV vaccine / mimotope / neutralizing antibody / phage library / HIV-1 |
|---|
| Research Abstract |
Development of an effective vaccine against Human Immunodeficiency Virus Type 1 (HIV-1) has been one of the most important research projects. We established a neutralizing monoclonal antibody, RC25 that was cross-reactive against approximately 60 % of claid B isolates of HIV-1. Using immuno-affinity chromatography conjugated with RC25 we successfully isolated 110 phage clones that specifically interacted with RC25. Six phage clones (NSV, APE, APS, SDF, YPW, YPL) were selected by detecting cross-reactivity to the other neutralizing antibodies of different specificity. These clones don t have an exact epitope (IGPXRA) associated with the binding of RC25. Instead, these peptides have mimotopes that resemble the antigenic structure(s) of gp120. However, immunization of animals with the synthetic peptides corresponded to the individual mimotope did not induce antibodies that could react and neutralize HIV. Because we thought that the antigenic structure of individual phage clone was broken in corresponding synthetic peptides we attempted to immunize rabbits with the phage clone itself. Weak but distinct reactivity and neutralizing activity of antibody induced by the immunization was observed for SF162. After screening several hundred clones we have focused on the 7 phage clones as the candidates for the minotopes. But none of them seemed to be ideal. Induction of broadly reactive neutralizing antibodies is deemed essential for the effective vaccine against HIV. Continuous effort for the development of antigen that induce cross-neutralizing antibodies should be supported with high priority.
|
