Smallpox (vaccinia) vaccine, live(Sanofi)

自 2022 年 5 月起，猴痘疫情在全球爆发。猴痘是由猴痘病毒引起的人畜共患病，与天花病毒等属同一家族，存在交叉免疫保护。全球停止天花疫苗接种后，人群对正痘病毒免疫力下降，使得猴痘防控形势严峻，疫苗研发迫在眉睫。 1、猴痘与猴痘病毒 猴痘病毒此前多在非洲热带雨林地区通过动物传播给人，2022 年后人际传播成为主要感染途径。其潜伏期 5 - 21 天，症状以皮肤和黏膜皮疹为主，是自限性疾病。病毒基因组为双链 DNA，分为两个进化分支，I 分支致病更严重。猴痘病毒早在 1970 年就出现首例人类感染病例，2022 年开始全球大流行，中国也出现了输入性病例和本土感染情况。 2、猴痘疫苗 已获批疫苗：美国、欧洲、日本和俄罗斯分别批准了 ACAM2000、JYNNEOS、LC16m8 和 OrthopoxVac 用于猴痘预防。ACAM2000 是第二代天花疫苗，不良反应多；JYNNEOS 安全性好但中和抗体水平较低；LC16m8 副作用少，可用于儿童；OrthopoxVac 免疫原性强，能有效预防猴痘。 其他潜在痘苗病毒疫苗：中国的痘苗病毒天坛株（VTT）有预防猴痘的潜力，其诱导的抗体可长期存在，但也有不良反应。通过基因编辑得到的非复制型天坛痘苗病毒（NTV）安全性更高，已获批开展猴痘疫苗临床试验。此外，KVAC103 自然减毒株和 NYVAC 重组疫苗也在研究中，不过 NYVAC 免疫原性较低。 亚单位、肽和核酸疫苗：全球利用基因工程技术研发新型猴痘疫苗。蛋白亚单位疫苗通过纯化目标蛋白制备，如多种蛋白组合免疫动物可产生保护作用；表位肽疫苗借助反向疫苗学选择抗原表位，能诱导有效免疫；核酸疫苗基于 DNA 或 mRNA 序列，可激发细胞和体液免疫，在动物实验中展现出良好效果。 3、结论与展望 目前基于痘苗病毒的 4 种疫苗已获批用于猴痘预防，但仍需临床试验验证其安全性和有效性。疫苗研发一方面要改进传统疫苗，另一方面要推进创新设计。同时，要保障猴痘疫苗的供应和储备。中国虽已开展相关研究，但与国际标准仍有差距，需加大投入，加快猴痘疫苗的研发进程。

Bavarian Nordic demonstrated non-inferiority between the freeze-dried and liquid-frozen formulations. Image credit: Shutterstock/ davide bonaldo. The US Food and Drug Administration (FDA) has approved the freeze-dried formulation of Bavarian Nordic’s smallpox and mpox vaccine in a move expected to provide flexibility in stockpiling the jab. Marketed as Jynneos in the US, the vaccine currently exists in a liquid-frozen formulation. These products require a temperature-controlled supply chain that keeps them frozen between production up until being used on a patient. Freeze-dried formulations have fewer supply chain limitations, conferring advantages such as easier transportation, storage conditions, and extended shelf life. Freeze drying is a dehydration process to extend its shelf life and molecular stability. The FDA approved Bavarian Nordic’s new formulation after the vaccine maker demonstrated comparability to the old formulation in terms of immune responses. The freeze-dried formulation is approved for the prevention of smallpox and mpox disease in adults aged 18 years and older. This included a Phase II trial in 651 healthy volunteers who were given two doses of either the liquid-frozen vaccine or the freeze-dried counterpart. No statistical differences were observed between the groups in immune responses and no serious adverse events were recorded, although the freeze-dried group did have slightly higher local reactions. Bavarian Nordic also supplied non-clinical and manufacturing to the FDA as part of the supplemental biologics licence application (sBLA) submitted in May 2024. The US Government has been working closely with Bavarian Nordic to ensure a stockpile of the vaccines is available in the event of a mpox outbreak. The country has been stockpiling since 2010 and ramped up efforts after the 2022-2023 outbreak, where the disease had spread to all 50 states. Bavarian Nordic is working closely with the US Biomedical Advanced Research and Development Authority (BARDA) to replenish the country’s vaccine stockpile. In 2017, BARDA awarded Bavarian Nordic a contract to develop a freeze-dried version of the vaccine with a longer shelf-life to replace the stockpile. In 2024, a follow-up $156.8m contract was awarded to support these efforts. Bavarian Nordic stated that manufacturing was initiated in 2024, and the first vaccines will be delivered later in 2025. Bavarian Nordic’s CEO Paul Chaplin said: “Today’s FDA approval represents a significant milestone in our development of this next generation of Jynneos and in our collaborative efforts with the US Government to strengthen public health security.” For a time, Jynneos was the only FDA-approved vaccine for the prevention of mpox. Emergent BioSolutions’ ACAM2000 then became the second vaccine for the infectious disease, winning FDA approval to prevent mpox in those at high risk of infection in August 2024. Bavarian Nordic’s product, also known as MVA-BN and Imvanex in other regions, has been a key pillar of fighting the ongoing mpox outbreak in Africa. The biotech has sent more than a million  doses of the vaccine to countries experiencing outbreaks and promised further ramp-ups in vaccine production. The World Health Organization (WHO) has said the mpox outbreak is still a public health emergency, as per a February update. There have been more than 100,000 cases globally in the ongoing outbreak of Clade II mpox. There have been four cases of Clade I mpox in the US, with the most recent two in New Hampshire and New York in February 2025.