Department of Biochemistry and Biophysics, University of North Carolina, 125 Mason Farm Road, 6230E Marisco Hall, Chapel Hill, NC 27599, USA.
Department of Microbiology and Immunology, University of North Carolina, 125 Mason Farm Road, 6230E Marisco Hall, Chapel Hill, NC 27599, USA.
Pathog Dis. 2019 Feb 1;77(1). doi: 10.1093/femspd/ftz003.
The four DENV serotypes are mosquito-borne pathogens that belong to the Flavivirus genus. These viruses present a major global health burden, being endemic in over 120 countries, causing ∼390 million reported infections yearly, with clinical symptoms ranging from mild fever to severe and potentially fatal hemorrhagic syndromes. Development of a safe and efficacious DENV vaccine is challenging because of the need to induce immunity against all four serotypes simultaneously, as immunity against one serotype can potentially enhance disease caused by a heterotypic secondary infection. So far, live-virus particle-based vaccine approaches struggle with inducing protective tetravalent immunity, while recombinant subunit approaches that use the envelope protein (E) as the major antigen, are gaining promise in preclinical studies. However, E-based subunits require further development and characterization to be used as effective vaccine antigens against DENV. In this review, we will address the shortcomings of recombinant E-based antigens and will discuss potential solutions to enhance E-based subunit antigen immunogenicity and vaccine efficacy.
登革热病毒共有 4 种血清型，均为蚊媒病原体，属于黄病毒属。这些病毒对全球健康造成了重大负担，在 120 多个国家流行，每年报告约 3.9 亿例感染病例，临床症状从轻微发热到严重和潜在致命的出血综合征不等。由于需要同时诱导针对所有 4 种血清型的免疫，因此开发安全有效的登革热病毒疫苗具有挑战性，因为针对一种血清型的免疫可能会增强异型二次感染引起的疾病。到目前为止，基于活病毒粒子的疫苗方法在诱导保护性四价免疫方面存在困难，而使用包膜蛋白 (E) 作为主要抗原的重组亚单位方法在临床前研究中显示出前景。然而，E 基亚单位需要进一步开发和表征，才能作为有效的登革热病毒疫苗抗原使用。在这篇综述中，我们将讨论重组 E 基抗原的缺点，并讨论增强 E 基亚单位抗原免疫原性和疫苗效力的潜在解决方案。
