Palmer Gene A, Brogdon Jennifer L, Constant Stephanie L, Tattersall Peter
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Virol. 2004 Feb;78(3):1101-8. doi: 10.1128/jvi.78.3.1101-1108.2004.
An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.
理想的疫苗递送系统应在单次给药后引发持久的保护作用，最好通过非侵入性途径给药，并且即使在接受者存在遗传性或获得性免疫抑制的情况下也应是安全的。我们利用自主细小病毒独特的生命周期开发了一种非增殖性疫苗平台，该平台似乎在单次接种后既能诱导启动免疫，又能持续增强保护性免疫反应。基于小鼠微小病毒（MVM）和LuIII之间的嵌合体构建了一种缺陷型细小病毒载体，该载体表达伯氏疏螺旋体表面蛋白A（OspA）而非其衣壳蛋白。将该载体包装到MVM嗜淋巴细胞衣壳中，并接种到未接触过抗原的C3H/HeNcr小鼠体内。静脉内或鼻内单次给予载体剂量进行疫苗接种，可引发高滴度的抗OspA特异性抗体，该抗体可提供针对活螺旋体攻击的保护作用，并在动物的整个生命周期内持续存在。如抗OspA免疫球蛋白G2a抗体以及OspA特异性CD4(+) T细胞优先产生γ干扰素所示，体液免疫和细胞介导的Th(+)1免疫均被诱导。
