Matano T, Kano M, Odawara T, Nakamura H, Takeda A, Mori K, Sato T, Nagai Y
AIDS Research Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-murayama, 208-0011, Tokyo, Japan.
Vaccine. 2000 Aug 1;18(28):3310-8. doi: 10.1016/s0264-410x(00)00122-5.
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.
在艾滋病疫苗策略中，减毒活疫苗可对致病性病毒感染产生良好抗性，但有引发疾病的潜在风险，而诸如DNA疫苗接种等更安全的复制缺陷型策略迄今未能预防疾病发作。在此，我们开发了一种新型DNA疫苗策略，以诱导无毒病毒的受限复制，并在猿猴免疫缺陷病毒（SIV）感染模型中对其进行评估。我们通过用嗜亲性Friend鼠白血病病毒（FMLV）env替换SIV env，构建了嵌合SIV（FMSIV），从而将其复制限制在表达FMLV受体（mCAT1）的细胞中。在缺乏mCAT1的灵长类细胞中，FMSIV不会复制，除非外源导入mCAT1。用FMSIV DNA和mCAT1表达质粒DNA对猕猴进行疫苗接种，比单独使用FMSIV DNA进行复制缺陷型对照疫苗接种更有效地诱导了SIV Gag特异性细胞免疫反应，并增强了对致病性SIV（mac239）攻击的抗性。该策略可能有助于开发针对各种致病性病毒的安全有效疫苗。
