Abstract:

A Public Health Emergency of International Concern (PHEIC) is defined by the World Health Organization (WHO) as “an extraordinary event which is determined to constitute a public health risk to other states through the international spread of disease and potentially requires a coordinated international response”. To date, WHO has declared seven PHEIC events, including the H1N1 influenza, Ebola, poliomyelitis, Zika, COVID-19 and mpox. Vaccination remains as an effective method in preventing infectious diseases. The International Health Regulations (IHR) Emergency Committee's recommendations for preventing or reducing the international spread of disease and avoiding unnecessary interference with international traffic include an emphases on the development of diagnostics and therapeutics for diseases, as well as the vaccine development. The mRNA vaccine represents a platform technology for the development of next-generation vaccines, and possesses distinct advantages, such as a shortened development cycle, scalable and cost-effective production, as well as enhanced amplification capacity, highlighting its potential in rapid responding to emerging and re-emerging infectious diseases. In recent decades, the development of mRNA synthesis technology and nucleic acid delivery system has facilitated the rapid development of mRNA vaccines and their clinical applications. Here, we overview the development of mRNA vaccines in response to the past PHEICs, and discuss challenges and trends in this regard. Currently, COVID-19 mRNA vaccines have been authorized for human use, while multiple mRNA vaccines against influenza, Zika, mpox and Ebola have been evaluated in clinical or pre-clinical studies. Despite their proven efficacy, there is still room for further improvement of the mRNA vaccines. The mRNA design, optimization, delivery, formulation, manufacturing, storage, and transportation can be further improved by integrating synthetic biology, biochemistry, artificial intelligence, and other multidisciplinary technologies. Although the emergence of the next PHEIC cannot be predicted with certainty, we are optimistic that the mRNA vaccine technology will play a pivotal role in preventing pandemics in the future. {L-End}

Key words: public health emergency of international concern (PHEIC), mRNA vaccine, viral infectious disease, influenza virus, Ebola virus, poliovirus, Zika virus, SARS-CoV-2, mpox virus

摘要：

“国际公共卫生紧急事件”（简称PHEIC）是指疾病的国际传播对其他国家构成公共卫生风险，需要采取协调一致的国际应对措施的不同寻常事件。迄今为止，世界卫生组织（WHO）一共宣布了7次PHEIC，包括甲型H1N1流感、埃博拉、脊髓灰质炎、寨卡、新型冠状病毒感染和猴痘疫情。疫苗是应对传染病疫情的有力武器，合成生物学的发展突破了传统疫苗存在的难点问题和技术瓶颈，为病毒性传染病防控提供了全新的思路，尤其是mRNA疫苗作为下一代疫苗研发的平台技术，具有安全性强、有效性良好、研发周期短、易规模化生产、易扩大产能等特点，在应对新突发传染病疫情方面具有明显的优势。目前，新冠mRNA疫苗已正式获批上市，针对流感、寨卡和猴痘病毒的多款mRNA疫苗已进入临床研究阶段，埃博拉mRNA疫苗处于临床前研究阶段，而针对脊髓灰质炎病毒尚无mRNA疫苗研究的报道。本文就历次PHEIC应对中mRNA疫苗的研发进展进行了详细梳理和评述，同时对mRNA疫苗应对PHEIC的未来发展趋势和挑战进行了展望和讨论。结合合成生物学、生物化学和人工智能等多学科技术对mRNA分子设计、高效递送以及疫苗生产和储存运输等进行优化，有望进一步提高mRNA疫苗的有效性和可及性。综上，尽管尚无法预知下一次PHEIC何时会出现，但当下一次PHEIC出现时，mRNA疫苗技术一定会成为人类防范PHEIC的有力武器。

关键词: 国际公共卫生紧急事件, mRNA疫苗, 病毒性传染病, 流感病毒, 埃博拉病毒, 脊髓灰质炎病毒, 寨卡病毒, 新冠病毒, 猴痘病毒