Coughlan Lynda, Mullarkey Caitlin, Gilbert Sarah
The Jenner Institute, University of Oxford, Oxford, UK.
J Pharm Pharmacol. 2015 Mar;67(3):382-99. doi: 10.1111/jphp.12350. Epub 2015 Jan 5.
Influenza is a viral respiratory disease causing seasonal epidemics, with significant annual illness and mortality. Emerging viruses can pose a major pandemic threat if they acquire the capacity for sustained human-to-human transmission. Vaccination reduces influenza-associated mortality and is critical in minimising the burden on the healthcare system. However, current vaccines are not always effective in at-risk populations and fail to induce long-lasting protective immunity against a range of viruses.
The development of 'universal' influenza vaccines, which induce heterosubtypic immunity capable of reducing disease severity, limiting viral shedding or protecting against influenza subtypes with pandemic potential, has gained interest in the research community. To date, approaches have focused on inducing immune responses to conserved epitopes within the stem of haemagglutinin, targeting the ectodomain of influenza M2e or by stimulating cellular immunity to conserved internal antigens, nucleoprotein or matrix protein 1.
Adenoviral vectors are potent inducers of T-cell and antibody responses and have demonstrated safety in clinical applications, making them an excellent choice of vector for delivery of vaccine antigens. In order to circumvent pre-existing immunity in humans, serotypes from non-human primates have recently been investigated. We will discuss the pre-clinical development of these novel vectors and their advancement to clinical trials.
流感是一种引起季节性流行的病毒性呼吸道疾病,每年导致大量发病和死亡。如果新兴病毒获得持续人传人的能力,可能构成重大的大流行威胁。接种疫苗可降低与流感相关的死亡率,对于减轻医疗系统负担至关重要。然而,目前的疫苗在高危人群中并不总是有效,并且无法诱导针对多种病毒的持久保护性免疫。
“通用”流感疫苗的研发已引起研究界的关注,这种疫苗可诱导异型免疫,能够减轻疾病严重程度、减少病毒脱落或预防具有大流行潜力的流感亚型。迄今为止,研究方法主要集中在诱导针对血凝素茎部保守表位的免疫反应、靶向流感病毒M2e的胞外域或通过刺激对保守内部抗原、核蛋白或基质蛋白1的细胞免疫。
腺病毒载体是T细胞和抗体反应的有效诱导剂,并且在临床应用中已证明其安全性,使其成为递送疫苗抗原的理想载体选择。为了规避人类中预先存在的免疫力,最近对来自非人类灵长类动物的血清型进行了研究。我们将讨论这些新型载体的临床前开发及其向临床试验的推进。