Chapman Rosamund, Rybicki Edward P
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South Africa.
Biopharming Research Unit, Department of Molecular & Cell Biology, University of Cape Town, PB X3 Rondebosch, Cape Town 7701, South Africa.
Vaccines (Basel). 2019 Jun 13;7(2):50. doi: 10.3390/vaccines7020050.
DNA vaccines are stable, safe, and cost effective to produce and relatively quick and easy to manufacture. However, to date, DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172 bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits, and macaques at 4-10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.
DNA疫苗生产稳定、安全且成本效益高，生产过程相对快速且简便。然而，尽管临床前研究结果令人鼓舞，但迄今为止，DNA疫苗在人体中的免疫原性相对较差。因此，人们研究了多种不同方法来提高DNA疫苗的免疫原性。这些方法包括使用改进的递送方法、佐剂、更强的启动子和增强子元件以增加抗原表达，以及对感兴趣的基因进行密码子优化。本综述描述了一种含有猪圆环病毒（PCV-1）增强子元件的DNA疫苗载体的构建和应用，该元件可显著提高重组抗原的表达和免疫原性，并可减少剂量。发现一个包含PCV-1衣壳蛋白启动子（Pcap）的172 bp区域以及其中一个较小的元件（PC；70 bp）具有同等效力。含有表达各种HIV-1抗原的Pcap区域的DNA疫苗在小鼠、兔子和猕猴中，以比通常使用剂量低4至10倍的剂量就具有高度免疫原性，并且在异源初免-加强免疫方案中非常有效。通过减少用于免疫的DNA量，可以克服向人体注射大量DNA的安全问题。
Zotero 插件
