Wang B, Dang K, Agadjanyan M G, Srikantan V, Li F, Ugen K E, Boyer J, Merva M, Williams W V, Weiner D B
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Vaccine. 1997 Jun;15(8):821-5. doi: 10.1016/s0264-410x(96)00259-9.
Mucosal immunity is the first defense system in protection against mucosal infection by sexually transmitted diseases and subsequent systemic dissemination of infection. Development of vaccines which can induce protective mucosal immunity would have great promise for preventing sexually transmitted diseases including AIDS. DNA vaccines have recently shown certain advantages over other types of vaccines in safety and elicitation of specific immune responses. We have hypothesized that direct delivery of a DNA plasmid coding the HIV-1 envelope (pcMN160) via mucosal routes will stimulate mucosal immunity against HIV-1. The expression of DNA plasmid inoculated intravaginally was detected in various tissues. Intravaginal inoculation of pcMN160 elicits production of vaginal immunoglobulins which specifically bind to the HIV-1 envelope and neutralize HIV-1 infectivity in vitro. These results indicate the feasibility of inducing mucosal immunity following mucosal inoculation of DNA vaccines. When coupled with systemic inoculation of appropriate DNA constructs, effective mucosal and systemic immunity may be generated.
黏膜免疫是抵御性传播疾病引起的黏膜感染及后续感染全身播散的第一道防御系统。研发能够诱导保护性黏膜免疫的疫苗对于预防包括艾滋病在内的性传播疾病具有巨大前景。DNA疫苗最近在安全性和引发特异性免疫反应方面显示出优于其他类型疫苗的某些优势。我们推测，通过黏膜途径直接递送编码HIV-1包膜的DNA质粒（pcMN160）将刺激针对HIV-1的黏膜免疫。检测了经阴道接种的DNA质粒在各种组织中的表达情况。经阴道接种pcMN160可引发阴道免疫球蛋白的产生，这些免疫球蛋白能特异性结合HIV-1包膜并在体外中和HIV-1的感染性。这些结果表明黏膜接种DNA疫苗后诱导黏膜免疫的可行性。当与适当的DNA构建体进行全身接种相结合时，可能会产生有效的黏膜和全身免疫。
