期刊
VIROLOGY
卷 372, 期 1, 页码 165-175出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2007.10.014
关键词
replication-defective virus; herpes; HSV; vaccine
类别
资金
- NIAID NIH HHS [R01 AI057552-01A1, R01 AI057552-02, R01 AI057552, AI 057552, R01 AI057552-03, R56 AI057552, R01 AI057552-04] Funding Source: Medline
The herpes simplex virus 2 dl5-29 replication-defective mutant virus has been shown to induce protective immunity in mice and both prophylactic and therapeutic immunity in guinea pigs. In an attempt to improve the efficacy of dl5-29 we disrupted its U(L)41 gene, producing the triple mutant virus dl5-29-41L. dl5-29-41L has a decreased ability to inhibit host cell protein synthesis and a reduced cytopathic effect on cultured cells. When used to immunize mice, dl5-29-41L elicited significantly stronger neutralizing antibody responses and significantly stronger CD4(+) and CD8(+) cellular immune responses than dl5-29. The enhanced immune responses corresponded with increased protective capacity in a murine model of genital herpes. The protective immunity elicited by either virus was very durable, protecting mice for at least 7 months. Furthermore, we show that cell lysate preparations of both viruses were significantly more efficacious than the corresponding extracellular virus preparations. (C) 2007 Elsevier Inc. All rights reserved.
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