論文 - 詳細
| RRC ID | 55889 |
|---|---|
| 著者 | Takayama-Ito M, Lim CK, Yamaguchi Y, Posadas-Herrera G, Kato H, Iizuka I, Islam MT, Morimoto K, Saijo M. |
| タイトル | Replication-incompetent rabies virus vector harboring glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge. |
| ジャーナル | PLoS Negl Trop Dis |
| Abstract |
BACKGROUND:Lymphocytic choriomeningitis virus (LCMV) causes a variety of diseases, including asymptomatic infections, meningitis, and congenital infections in the fetus of infected mother. The development of a safe and effective vaccine against LCMV is imperative. This study aims to develop a new candidate vaccine against LCMV using a recombinant replication-incompetent rabies virus (RV) vector. METHODOLOGY/PRINCIPAL FINDINGS:In this study, we have generated a recombinant deficient RV expressing the LCMV glycoprotein precursor (GPC) (RVΔP-LCMV/GPC) which is lacking the RV-P gene. RVΔP-LCMV/GPC is able to propagate only in cells expressing the RV-P protein. In contrast, the LCMV-GPC can be expressed in general cells, which do not express RV-P protein. The ability of RVΔP-LCMV/GPC to protect mice from LCMV infection and induce cellular immunity was assessed. Mice inoculated intraperitoneally with RVΔP-LCMV/GPC showed higher survival rates (88.2%) than those inoculated with the parental recombinant RV-P gene-deficient RV (RVΔP) (7.7%) following a LCMV challenge. Neutralizing antibody (NAb) against LCMV was not induced, even in the sera of surviving mice. CD8+ T-cell depletion significantly reduced the survival rates of RVΔP-LCMV/GPC-inoculated mice after the LCMV challenge. These results suggest that CD8+ T cells play a major role in the observed protection against LCMV. In contrast, NAbs against RV were strongly induced in sera of mice inoculated with either RVΔP-LCMV/GPC or RVΔP. In safety tests, suckling mice inoculated intracerebrally with RVΔP-LCMV/GPC showed no symptoms. CONCLUSIONS/SIGNIFICANCE:These results show RVΔP-LCMV/GPC might be a promising candidate vaccine with dual efficacy, protecting against both RV and LCMV. |
| 巻・号 | 12(4) |
| ページ | e0006398 |
| 公開日 | 2018-4-1 |
| DOI | 10.1371/journal.pntd.0006398 |
| PII | PNTD-D-17-01247 |
| PMID | 29659579 |
| PMC | PMC5901774 |
| MeSH | Animals Female Gene Expression Genetic Vectors / genetics Genetic Vectors / metabolism Glycoproteins / administration & dosage Glycoproteins / genetics Glycoproteins / immunology* Humans Lymphocytic Choriomeningitis / immunology Lymphocytic Choriomeningitis / prevention & control* Lymphocytic Choriomeningitis / virology Lymphocytic choriomeningitis virus / genetics Lymphocytic choriomeningitis virus / immunology* Mice Mice, Inbred C57BL Rabies virus / genetics Rabies virus / physiology* Viral Proteins / administration & dosage Viral Proteins / genetics Viral Proteins / immunology* Viral Vaccines / administration & dosage Viral Vaccines / genetics Viral Vaccines / immunology* Virus Replication |
| IF | 4.487 |
| 引用数 | 2 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |