Wang S W, Kozlowski P A, Schmelz G, Manson K, Wyand M S, Glickman R, Montefiori D, Lifson J D, Johnson R P, Neutra M R, Aldovini A
Department of Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Virol. 2000 Nov;74(22):10514-22. doi: 10.1128/jvi.74.22.10514-10522.2000.
We report a pilot evaluation of a DNA vaccine producing genetically inactivated simian immunodeficiency virus (SIV) particles in primates, with a focus on eliciting mucosal immunity. Our results demonstrate that DNA vaccines can be used to stimulate strong virus-specific mucosal immune responses in primates. The levels of immunoglobulin A (IgA) detected in rectal secretions of macaques that received the DNA vaccine intradermally and at the rectal mucosa were the most striking of all measured immune responses and were higher than usually achieved through natural infection. However, cytotoxic T lymphocyte responses were generally low and sporadically present in different animals. Upon rectal challenge with cloned SIVmac239, resistance to infection was observed, but some animals with high SIV-specific IgA levels in rectal secretions became infected. Our results suggest that high levels of IgA alone are not sufficient to prevent the establishment of chronic infection, although mucosal IgA responses may have a role in reducing the infectivity of the initial viral inoculum.
我们报告了一项在灵长类动物中对产生基因灭活猴免疫缺陷病毒（SIV）颗粒的DNA疫苗进行的初步评估，重点是引发黏膜免疫。我们的结果表明，DNA疫苗可用于刺激灵长类动物产生强烈的病毒特异性黏膜免疫反应。在经皮内和直肠黏膜接种DNA疫苗的猕猴直肠分泌物中检测到的免疫球蛋白A（IgA）水平，是所有测量的免疫反应中最为显著的，且高于通常通过自然感染所达到的水平。然而，细胞毒性T淋巴细胞反应总体较低，且在不同动物中偶尔出现。在用克隆的SIVmac239进行直肠攻击后，观察到了对感染的抵抗力，但一些直肠分泌物中SIV特异性IgA水平较高的动物仍被感染。我们的结果表明，仅高水平的IgA不足以预防慢性感染的建立，尽管黏膜IgA反应可能在降低初始病毒接种物的感染性方面发挥作用。
