Induction of protective immunity against pathogenic simian immunodeficiency virus by a foreign receptor-dependent replication of an engineered avirulent virus

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• 作者：Matano ; Tetsuro ; Kano ; Munehide ; Odawara ; Takashi ; Nakamura ; Hiromi ; Takeda ; Akiko ; Mori ; Kazuyasu ; et. al.
• 关键词：AIDS vaccine ; SIV ; Cellular immune response
• 刊名：Vaccine
• 出版年：2000
• 出版时间：August 1, 2000
• 年：2000
• 卷：18
• 期：28
• 页码：3310-3318
• 全文大小：298 K

文摘

In AIDS vaccine strategies, live attenuated vaccines can confer good resistance against pathogenic virus infections but have the potential risk of inducing disease, whereas safer replication-negative strategies such as DNA vaccinations have so far failed to prevent the disease onset. Here, we developed a novel DNA vaccine strategy to induce restricted replication of an avirulent virus and evaluated it in a simian immunodeficiency virus (SIV) infection model. We generated a chimeric SIV, FMSIV, by replacing SIV env with ecotropic Friend murine leukemia virus (FMLV) env to confine its replication to FMLV receptor (mCAT1)-expressing cells. In primate cells lacking mCAT1, FMSIV did not replicate unless mCAT1 was introduced exogenously. Vaccination to macaques with both the FMSIV DNA and the mCAT1-expression plasmid DNA induced SIV Gag-specific cellular immune responses and resistance against pathogenic SIV_mac239 challenge more efficiently than the replication-negative control vaccination with the FMSIV DNA alone. This strategy may be useful for development of safe and effective vaccines against various kinds of pathogenic viruses.