Gene Therapy and Immunogenicity Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration,Bethesda, Maryland, United States of America.
PLoS One. 2013;8(3):e55435. doi: 10.1371/journal.pone.0055435. Epub 2013 Mar 11.
Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.
在最近研究的大约 1000 种来自黑猩猩和倭黑猩猩的腺病毒中,Pan 腺病毒 3 型(PanAd3,从倭黑猩猩 Pan paniscus 中分离出来)是一种疫苗载体,具有最佳特性之一,它具有强大的转基因免疫原性,同时在人群中具有最小的预先存在的免疫性。在这项研究中,我们将一个表达保守流感抗原核蛋白(NP)和基质 1(M1)融合蛋白的转基因插入到复制缺陷的 PanAd3 中。然后,我们在小鼠模型中研究了抗体和 T 细胞反应以及对挑战感染的保护作用。单次鼻腔内给予 PanAd3-NPM1 疫苗可诱导强烈的抗体和 T 细胞反应,并可预防高剂量致死性流感病毒的挑战。因此,PanAd3 是疫苗的一种有前途的候选载体,包括通用流感疫苗。