The Use of Adeno-associated virus (AAV) in Vaccine Development

Keh Min Xuan, Nur Ain Mohd Asri, Rafeah Suppian, Norazmi Mohd Nor, M. Azlan, F. Camacho
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Abstract

  Adeno-associated virus (AAV) is a very tiny (20-26 nm) icosahedral and non-enveloped virus, and it belongs to the Parvoviridae family. AAV vectors are the most widely used option for gene therapy and delivery of therapeutic antibodies due to their relatively low immunogenicity, high safety profile, broad tropism, and their tendency to maintain long-term gene expression [1]. AVV vectors are developed by transfection of human embryonic kidney (HEK) 293 T cells with transgene, packaging and helper plasmids [2]. Several clinical studies have investigated the use of AAV vectors for gene therapy in treating of Parkinson’s disease, Alzheimer’s disease, heart disease, and prostate cancer [3]. AAV vectors have previously been used to treat muscular diseases, but in recent years, their usage as vaccine vectors to cure or prevent infectious diseases including HIV, HPV, and influenza has expanded [4].   Here, we discuss the advantages and disadvantages of the use of AAV in vaccine development, and future approaches in improving the drawbacks caused by AAV-based vaccines. Numerous animal investigations have been conducted to explore vaccine vectors against various illnesses, suggesting a possibility for AAV-based vaccinations. Clinical studies on humans are, however, uncommon because, in contrast to other viral vectors, AAV induces a poor humoral and cellular immune response. Additionally, infectious vaccinations often target a large group of healthy individuals across a variety of ages, including children and teenagers. Therefore, compared to AAV-based gene therapies, vaccinations based on AAV vectors need to be more cost-effective and need more robust safety control.   According to several research, AAV vector vaccines have been shown to induce a stronger or longer lasting antibody response in comparison to other vaccination approaches, such as DNA, recombinant proteins, inactivated viruses, or virus-like particles (VLPs) [5]. However, AAV vectors are thought to have a low immunogenic profile in comparison to other viral vectors. The main limitations of AAV vectors are their low transgenic capacity and widespread pre-existing immunity in humans [6]. Currently, strategies for improving AAV immunogenicity and circumventing pre-existing immunity are actively being investigated. The research undertaken so far have highlighted numerous significant benefits of AAV vectors for immunisation. Despite all the advantages, there are still a variety of challenges that limit the use of these vectors as a vaccine in humans. Thus, it is necessary to overcome these challenges in order to make AAV-based vaccines effective.
腺相关病毒(AAV)在疫苗开发中的应用
腺相关病毒(Adeno-associated virus, AAV)是一种体积极小(20 ~ 26 nm)的二十面体非包膜病毒,属于细小病毒科。AAV载体由于其相对较低的免疫原性、较高的安全性、广泛的趋向性以及维持长期基因表达的倾向,是基因治疗和治疗性抗体递送中最广泛使用的选择。用转基因、包装和辅助质粒[2]转染人胚胎肾(HEK) 293 T细胞制备AVV载体。一些临床研究已经探讨了利用AAV载体进行基因治疗,以治疗帕金森病、阿尔茨海默病、心脏病和前列腺癌。AAV载体以前被用于治疗肌肉疾病,但近年来,它们作为疫苗载体用于治疗或预防包括艾滋病毒、HPV和流感在内的传染病的用途已经扩大。在这里,我们讨论了在疫苗开发中使用AAV的优点和缺点,以及未来改进AAV疫苗所带来的缺点的方法。已经进行了大量动物调查,以探索针对各种疾病的疫苗载体,这表明基于aav的疫苗接种是可能的。然而,对人类的临床研究并不常见,因为与其他病毒载体相比,AAV诱导的体液和细胞免疫反应较差。此外,传染病疫苗通常针对不同年龄的一大群健康个体,包括儿童和青少年。因此,与基于AAV的基因疗法相比,基于AAV载体的疫苗接种需要更具成本效益,并且需要更强大的安全控制。根据几项研究,与其他疫苗接种方法(如DNA、重组蛋白、灭活病毒或病毒样颗粒(vlp)[5])相比,AAV载体疫苗已被证明可诱导更强或更持久的抗体反应。然而,与其他病毒载体相比,AAV载体被认为具有较低的免疫原性。AAV载体的主要限制是其转基因能力低和在人类中广泛存在的预先免疫。目前,正在积极研究提高AAV免疫原性和规避已有免疫的策略。迄今开展的研究强调了AAV载体用于免疫的许多重要益处。尽管有这些优点,但仍然存在各种挑战,限制了这些媒介作为人类疫苗的使用。因此,为了使基于aav的疫苗有效,有必要克服这些挑战。
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