Induction of mucosal protection against primary, heterologous simian immunodeficiency virus by a DNA vaccine
Induction of mucosal protection against primary, heterologous simian immunodeficiency virus by a DNA vaccine
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DOI：
10.1128/jvi.76.7.3309-3317.2002
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发表时间：
2002-04-01
影响因子：
5.4
通讯作者：
Murphey-Corb, M
中科院分区：
文献类型：
--
作者：
Fuller, DH;Rajakumar, PA;Murphey-Corb, M
一种有效的人类免疫缺陷病毒（HIV）疫苗应能防止遗传差异分离株的粘膜传播。作为一种安全的减毒活疫苗替代品，研究了猴免疫缺陷病毒（SIV）17E-Fr株（SIV/17E-Fr）gag-pol-env DNA疫苗在恒河猴体内的免疫原性和保护效果。在多次免疫后观察到显著水平的细胞毒性T淋巴细胞（CTL），但血清抗体应答低至检测不到。SIV特异性粘膜抗体和CTL也分别在直肠冲洗液和肠道相关淋巴组织中检测到。用SIV毒株DeltaB670（SIV/DeltaB670）直肠内攻毒接种疫苗和未接种对照猴，SIV毒株DeltaB670是一种主要分离株，其env与疫苗毒株的env有15%的差异。7名疫苗接种者中有4名受保护免受感染，这是通过无法识别外周血中的病毒RNA或DNA序列以及攻毒后不存在记忆抗体反应来确定的。这是第一次报告粘膜保护对主要致病性，异源分离的SIV通过使用商业上可行的疫苗的方法。这些结果支持进一步开发用于保护免受HIV感染的DNA疫苗。
An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/ 17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/ DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV.