a Division of Infectious Diseases, Department of Medicine, Department of Immunology, Department of Molecular Medicine , Mayo Clinic , Rochester , MN , USA.
Expert Rev Vaccines. 2018 Feb;17(2):163-173. doi: 10.1080/14760584.2018.1419067. Epub 2018 Jan 18.
Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines.
This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared.
The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.
传统的灭活疫苗和蛋白疫苗能产生强烈的抗体,但难以产生 T 细胞反应。减毒病原体疫苗既能产生抗体,又能产生 T 细胞反应,但有引发其预防疾病的风险。新型的基于基因的疫苗能驱动这两种反应,同时避免感染的风险。虽然这些复制缺陷型 (RD) 疫苗在小动物身上效果良好,但在人类身上可能效果较弱,因为它们不像更有效的复制型 (RC) 疫苗那样复制抗原基因。RC 疫苗能产生更强的免疫反应,但也有引发自身感染的风险。为了规避这些问题,我们开发了单周期腺病毒 (SC-Ad) 载体,可扩增疫苗基因,同时避免感染的风险。本综述将讨论这些载体及其作为疫苗的应用前景。
本综述提供了不同类型疫苗的背景信息。描述了基因疫苗的优势及其复制抗原基因的能力。讨论了腺病毒载体,并与其他疫苗类型进行了比较。比较了复制缺陷型、单周期和复制型 Ad 疫苗。
讨论了这些疫苗在对抗传染病和癌症疫苗方面的潜在应用。我们建议从复制缺陷型疫苗转向更强大的复制型或单周期疫苗。