Outbreaks of mpox have been increasing over the past few decades. The modified vaccinia Ankara (MVA)-based vaccine is effective against mpox; however, issues such as incomplete immunity and uncertainty of cross-protection to more virulent strains necessitate the investigation of improved vaccines. In Cell, Mucker et al. compare the protection against mpox conferred by two different vaccines in non-human primates. They tested the mRNA-LNP MPXV vaccine, mRNA-1769, that expresses four mpox virus (MPXV) antigens and compared it with the live-attenuated Orthopoxvirus vaccine MVA in cynomolgus macaques after a lethal challenge with MPXV clade I Z79. Both vaccines provided robust protection against lethal MPXV challenge, but mRNA-1769 provided better protection against symptoms such as weight loss, lesion number and duration, and viral replication. By analyzing the humoral immune response, the researchers found that mRNA-1769 immunization elicited robust, neutralizing and broadly cross-reactive antibody responses. Using systems serology, IgG subclass responses and Fc-receptor-binding profiles, the authors found variability in the antibody functions and profiles across vaccine modalities. To define the antibody mechanisms that account for attenuation of disease, the authors performed a multivariate correlates analysis and demonstrated that the effector functions of antibodies specific for extracellular virions and mature virions are important for the reduction of the formation of lesions. This is an important step towards finding a better vaccine for mpox, although more research is needed to understand whether mRNA vaccines can provide the needed immunity for mpox control in humans.

Original reference: Cell https://doi.org/10.1016/j.cell.2024.08.043 (2024)

在过去的几十年里，猴痘的爆发一直在增加。基于安卡拉牛痘 （MVA） 的改良疫苗对 mpox 有效;然而，免疫不完全和对毒性更强的菌株的交叉保护的不确定性等问题需要研究改进的疫苗。在 Cell 中，Mucker 等人比较了两种不同疫苗在非人类灵长类动物中对 mpox 的保护作用。他们测试了表达四种 mpox 病毒 （MPXV） 抗原的 mRNA-LNP MPXV 疫苗 mRNA-1769，并将其与在受到 MPXV 分支 I Z79 致命攻击后的食蟹猴中的正痘病毒减毒活疫苗 MVA 进行了比较。两种疫苗都对致命的 MPXV 攻击提供了强大的保护，但 mRNA-1769 对体重减轻、病变数量和持续时间以及病毒复制等症状提供了更好的保护。通过分析体液免疫反应，研究人员发现 mRNA-1769 免疫引发了强烈的中和和广泛交叉反应性的抗体反应。使用系统血清学、IgG 亚类反应和 Fc 受体结合谱，作者发现不同疫苗模式的抗体功能和谱存在差异。为了定义解释疾病减轻的抗体机制，作者进行了多变量相关分析，并证明细胞外病毒粒子和成熟病毒粒子特异性抗体的效应功能对于减少病变的形成很重要。这是寻找更好的 mpox 疫苗的重要一步，尽管需要更多的研究来了解 mRNA 疫苗是否可以为人类 mpox 控制提供所需的免疫力。

Original reference: Cell https://doi.org/10.1016/j.cell.2024.08.043 (2024)