Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States.
Division of Cancer & Genetics, Division of Infection & Immunity, School of Medicine, Cardiff University, Wales, United Kingdom.
Front Immunol. 2021 Jan 29;11:607333. doi: 10.3389/fimmu.2020.607333. eCollection 2020.
It is evident that the emergence of infectious diseases, which have the potential for spillover from animal reservoirs, pose an ongoing threat to global health. Zoonotic transmission events have increased in frequency in recent decades due to changes in human behavior, including increased international travel, the wildlife trade, deforestation, and the intensification of farming practices to meet demand for meat consumption. Influenza A viruses (IAV) possess a number of features which make them a pandemic threat and a major concern for human health. Their segmented genome and error-prone process of replication can lead to the emergence of novel reassortant viruses, for which the human population are immunologically naïve. In addition, the ability for IAVs to infect aquatic birds and domestic animals, as well as humans, increases the likelihood for reassortment and the subsequent emergence of novel viruses. Sporadic spillover events in the past few decades have resulted in human infections with highly pathogenic avian influenza (HPAI) viruses, with high mortality. The application of conventional vaccine platforms used for the prevention of seasonal influenza viruses, such as inactivated influenza vaccines (IIVs) or live-attenuated influenza vaccines (LAIVs), in the development of vaccines for HPAI viruses is fraught with challenges. These issues are associated with manufacturing under enhanced biosafety containment, and difficulties in propagating HPAI viruses in embryonated eggs, due to their propensity for lethality in eggs. Overcoming manufacturing hurdles through the use of safer backbones, such as low pathogenicity avian influenza viruses (LPAI), can also be a challenge if incompatible with master strain viruses. Non-replicating adenoviral (Ad) vectors offer a number of advantages for the development of vaccines against HPAI viruses. Their genome is stable and permits the insertion of HPAI virus antigens (Ag), which are expressed following vaccination. Therefore, their manufacture does not require enhanced biosafety facilities or procedures and is egg-independent. Importantly, Ad vaccines have an exemplary safety and immunogenicity profile in numerous human clinical trials, and can be thermostabilized for stockpiling and pandemic preparedness. This review will discuss the status of Ad-based vaccines designed to protect against avian influenza viruses with pandemic potential.
显然，具有从动物宿主溢出潜力的传染病的出现对全球健康构成持续威胁。近几十年来，由于人类行为的变化，包括国际旅行增加、野生动植物贸易、森林砍伐以及为满足肉类消费需求而加强农业实践，人畜共患病传播事件的频率有所增加。甲型流感病毒 (IAV) 具有多种特征，使其成为大流行威胁和人类健康的主要关注点。它们分段的基因组和易错复制过程可导致新型重组病毒的出现，而人类对此类病毒普遍缺乏免疫力。此外，IAV 感染水生鸟类和家畜以及人类的能力增加了重组和随后新型病毒出现的可能性。过去几十年中偶尔发生的溢出事件导致人类感染高致病性禽流感 (HPAI) 病毒，死亡率很高。用于预防季节性流感病毒的常规疫苗平台（如灭活流感疫苗 (IIV) 或减毒活流感疫苗 (LAIV)）在开发 HPAI 病毒疫苗方面应用存在诸多挑战。这些问题与在增强的生物安全控制下进行制造以及在鸡胚中繁殖 HPAI 病毒的困难有关，因为它们在鸡蛋中具有致死倾向。通过使用更安全的骨架（如低致病性禽流感病毒 (LPAI)）来克服制造障碍，如果与主株病毒不兼容，也可能是一个挑战。非复制型腺病毒 (Ad) 载体为开发针对 HPAI 病毒的疫苗提供了多项优势。它们的基因组稳定，允许插入 HPAI 病毒抗原 (Ag)，这些抗原在接种后表达。因此，它们的制造不需要增强的生物安全设施或程序，也不需要鸡蛋。重要的是，Ad 疫苗在许多人类临床试验中具有出色的安全性和免疫原性，并且可以进行热稳定化以用于储备和大流行准备。本综述将讨论针对具有大流行潜力的禽流感病毒设计的基于 Ad 的疫苗的现状。
