Vaccines against mpox: MVA-BN and LC16m8

Global outbreaks involving mpox clade IIb began in mid-2022. Today, clade IIb and clade I outbreaks continue. Reliable mpox vaccines can prevent serious mpox disease and death.
Globally, two vaccines hold mpox indications, regardless of mpox viral clade: MVA-BN (Bavarian Nordic) and LC16m8 (KM Biologics). This review summarizes the human and pivotal animal data establishing safety and efficacy for MVA-BN and LC16m8, including real-world evidence gathered during mpox outbreaks from 2022 through 2024.
Some regulatory decisions for MVA-BN and LC16m8 followed pathways based on surrogate outcomes, including lethal-challenge studies in nonhuman primates, among other atypical aspects. Nonetheless, MVA-BN and LC16m8 hold unencumbered registration in multiple countries. Effectiveness of MVA-BN as primary preventive vaccination (PPV) in humans against clade IIb mpox is clear from real-world studies; effectiveness of LC16m8 against clade IIb is likely from surrogate endpoints. Effectiveness of MVA-BN and LC16m8 as PPV against more-lethal clade I is likely, based on animal-challenge studies with multiple orthopoxvirus species and other studies. Both vaccines have solid safety records. MVA-BN’s replication incompetence favors adoption, whereas LC16m8 has more pediatric data. Additional real-world evidence, in additional geographic settings and special populations (e.g. pregnancy, immune suppression, atopic dermatitis), is needed.
Mpox outbreaks spread
globally in 2022, hospitalizing many people. Many recent mpox cases in Africa
occur in children. Two vaccines, known as MVA-BN and LC16m8, can help prevent mpox.
MVA-BN protects
animals from lethal doses of mpox and similar viruses. During outbreaks, MVA-BN
lowered the chance of mpox disease by 62% to 85%. In people already exposed to mpox,
MVA-BN reduced disease risk by 20%. MVA-BN may help reduce how serious mpox
cases are, even if this vaccine does not block infection fully. MVA-BN cannot
grow inside the body, making it very safe, even in children. Side effects
include pain, redness, swelling, and itching. Some people feel muscle pain, headache,
fatigue, nausea, or chills after vaccination. Several million people have
received MVA-BN so far, including thousands of people living with HIV.
LC16m8 protects
animals from lethal doses of mpox and similar viruses. There are not much data about
LC16m8 used during mpox outbreaks. LC16m8 contains a weakened virus. Side
effects include fever, fatigue, redness, swollen lymph nodes, and itching.
Vaccine virus can spread to other parts of the body. Over 90,000 people have
received LC16m8 so far. No significant safety signals were found after these
doses, including 50,000 children. People who are immunosuppressed, have certain
skin diseases, or are pregnant should not be given LC16m8.
Health officials recommend mpox vaccine for people at risk, including
children.

2022年中期，涉及猴痘（mpox）进化分支（clade）IIb的全球疫情首次暴发。时至今日，猴痘进化分支IIb与进化分支I的疫情仍在持续。可靠的猴痘疫苗可预防重症猴痘疾病与死亡。
全球范围内，有两款疫苗获批猴痘适应症，不受猴痘病毒进化分支限制：MVA-BN（巴伐利亚北欧公司，Bavarian Nordic）与LC16m8（KM生物制药公司，KM Biologics）。本综述汇总了证实MVA-BN与LC16m8安全性与有效性的人体及关键动物实验数据，涵盖2022年至2024年猴痘疫情期间收集的真实世界证据（real-world evidence）。
MVA-BN与LC16m8的部分监管审批流程基于替代终点（surrogate outcomes）制定，其中包括非人灵长类（nonhuman primates）致死攻击实验（lethal-challenge studies）等非传统审批路径。尽管如此，两款疫苗已在多国获得无限制注册资质。真实世界研究已明确证实，MVA-BN作为初次预防接种（primary preventive vaccination, PPV）对猴痘进化分支IIb的预防有效性；而LC16m8针对猴痘进化分支IIb的有效性则通过替代终点得以间接推断。基于针对多种正痘病毒（orthopoxvirus）的动物攻击实验及其他研究，两款疫苗作为初次预防接种针对致死性更强的猴痘进化分支I的有效性同样可被间接推断。两款疫苗均具备扎实的安全记录：MVA-BN因不具备复制能力而更易于推广，LC16m8则拥有更多儿科人群相关研究数据。未来仍需在更多地理区域及特殊人群（如孕妇、免疫抑制人群、特应性皮炎（atopic dermatitis）患者）中补充收集真实世界证据。
2022年，猴痘疫情在全球范围内扩散，导致大量患者住院治疗。近期非洲地区的多数猴痘病例均发生于儿童群体。两款分别名为MVA-BN与LC16m8的疫苗可有效预防猴痘感染。
MVA-BN可使动物免受致死剂量猴痘及同类病毒的感染。疫情期间，接种MVA-BN可使猴痘发病风险降低62%至85%；对于已暴露于猴痘病毒的人群，该疫苗可将发病风险降低20%。即便无法完全阻断感染，MVA-BN仍可有效减轻猴痘患者的病情严重程度。由于MVA-BN无法在人体内复制，因此即便用于儿童群体也具备极高的安全性。其常见不良反应包括接种部位疼痛、红斑、肿胀与瘙痒；部分接种者还会出现肌肉痛、头痛、乏力、恶心或寒战等全身症状。截至目前，已有数百万人群接种了MVA-BN，其中包括数千名艾滋病病毒感染者。
LC16m8可使动物免受致死剂量猴痘及同类病毒的感染。目前关于LC16m8在猴痘疫情中应用的相关数据较为有限。该疫苗搭载的是减毒活病毒（weakened virus），常见不良反应包括发热、乏力、接种部位红斑、淋巴结肿大与瘙痒。疫苗病毒可扩散至身体其他部位。截至目前，已有超过9万人接种了LC16m8，其中包括5万名儿童，且未观察到显著的安全信号。免疫功能低下、患有特定皮肤疾病或妊娠人群禁用LC16m8。
卫生官员建议包括儿童在内的高危人群接种猴痘疫苗。