2001 Fiscal Year Final Research Report Summary
Development of Broadly Reactive Influenza DNA Vaccine
| Project/Area Number |
11470117
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Public health/Health science
|
|---|
| Research Institution | Osaka Prefectural Institute of Public Health |
|---|
Principal Investigator |
OKUNO Yoshinobu Osaka Prefectural Institute of Public Health, Department of Public Health, Head of Division of Virology, 公衆衛生部, ウイルス課長 (30112064)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ITOH Masae Osaka Prefectural Institute of Public Health, Department of Public Health, Senior researcher, 公衆衛生部, 主任研究員 (10201328)
KASE Tetsuo Osaka Prefectural Institute of Public Health, Department of Public Health, Senior researcher, 公衆衛生部, 主任研究員 (10175276)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | influenza / DNA vaccine / hemagglutinin / neutralizing epitope |
|---|
| Research Abstract |
Hemagglutinin protein (HA) of influenza virus is divided into two parts, the globular head and the stem regions, structurally. We have demonstrated that there is a conserved neutralizing epitope in the stem region of HA. To utilize the epitope we tried to construct the CDNA encoding headless HA, and it was applied for broadly reactive influenza DNA vaccine.
Before the previous year, the mice immunized with the DNA vaccine containing expression vector, PEF-BOS, did not induce effective immune responses against influenza virus. Therefore, this year the expression vector was replaced by pNOW-GKT that can express proteins in high efficacy, and the effect of the DNA vaccine was studied by measuring antibody titers and by a challenge test.
The vector was inserted by CDNA encoding full-size HA gene or headless HA gene, and mice were immunized two times with the DNA vaccine 3 weeks apart by a gene gun. Two weeks after the second immunization, the mice were challenged by A/FM/1/47(H1N1) strain that had been adapted in mouse lung. Control mice immunized with vector only showed significant reduction of body weight and half of them were died. Whereas all the mice immunized with the full-size HA gene were alive without showing loss of body weight. Although 20 % of the mice immunized with headless HA gene were died, the alive mice did not show loss of body weight. When serum antibody in the mice were measured by the neutralization test and ELISA, increase in titers were observed in mice immunized with full-size HA gene but not with headless HA gene. These results seem to indicate that the DNA vaccine with headless HA gene induces cellular immunity more efficiently than humoral immunity.
|
