Barouch Dan H, Nabel Gary J
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Hum Gene Ther. 2005 Feb;16(2):149-56. doi: 10.1089/hum.2005.16.149.
Recombinant adenovirus (rAd) vectors have received considerable attention for gene therapy because of their high transduction efficiency. However, recombinant gene expression from rAd vectors elicits rapid and potent immune responses to foreign transgene products. Such immunogenicity limits the duration of transgene expression and poses a major challenge to the use of rAd vectors for gene therapy. In contrast, the inherent immunogenicity of these vectors is a desirable feature for vaccine development. The immunogenicity and protective efficacy of rAd vector-based vaccines have now been demonstrated in a number of animal models, and rAd vaccines for a variety of pathogens are currently being explored in early-phase clinical trials. In this review, we describe progress in the development of rAd vector-based vaccines with a focus on human immunodeficiency virus type 1.
重组腺病毒(rAd)载体因其高转导效率而在基因治疗中受到广泛关注。然而,rAd载体的重组基因表达会引发针对外源转基因产物的快速而强烈的免疫反应。这种免疫原性限制了转基因表达的持续时间,对将rAd载体用于基因治疗构成了重大挑战。相比之下,这些载体固有的免疫原性却是疫苗开发中一个理想的特性。基于rAd载体的疫苗的免疫原性和保护效力现已在多种动物模型中得到证实,目前多种针对不同病原体的rAd疫苗正处于早期临床试验阶段。在本综述中,我们将描述基于rAd载体的疫苗的开发进展,重点关注1型人类免疫缺陷病毒。