A Spread-Deficient Cytomegalovirus for Assessment of First-Target Cells in Vaccination
A Spread-Deficient Cytomegalovirus for Assessment of First-Target Cells in Vaccination
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DOI：
10.1128/jvi.02696-09
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发表时间：
2010-08-01
影响因子：
5.4
通讯作者：
Sacher, Torsten
中科院分区：
文献类型：
--
作者：
Mohr, Christian Andreas;Arapovic, Jurica;Sacher, Torsten
Human cytomegalovirus (HCMV) is a human pathogen that causes severe disease primarily in the immunocompromised or immunologically immature individual. To date, no vaccine is available. We describe use of a spread-deficient murine CMV (MCMV) as a novel approach for betaherpesvirus vaccination. To generate a spread-deficient MCMV, the conserved, essential gene M94 was deleted. Immunization with MCMV-Delta M94 is apathogenic and protective against wild-type challenge even in highly susceptible IFN alpha beta R-/- mice. MCMV-Delta M94 was able to induce a robust CD4(+) and CD8(+) T-cell response as well as a neutralizing antibody response comparable to that induced by wild-type infection. Endothelial cells were identified as activators of CD8(+) T cells in vivo. Thus, the vaccination with a spread-deficient betaherpesvirus is a safe and protective strategy and allows the linkage between cell tropism and immunogenicity. Furthermore, genomes of MCMV-Delta M94 were present in lungs 12 months after infection, revealing first-target cells as sites of genome maintenance.
