Wiedemann Aurélie, Surénaud Mathieu, Hubert Mathieu, Lopez Zaragoza José-Luis, Ribeiro Alexandre, Rodrigues Cécile, Foucat Emile, Diombera Harouna, Krief Corinne, Schwartz Olivier, Lelièvre Jean-Daniel, Lévy Yves
Vaccine Research Institute, Université Paris-Est Créteil, Créteil, France.
INSERM U955, Institut Mondor de Recherche Biomedicale, Team Lévy, Créteil, France.
J Immunol. 2025 Feb 1;214(2):211-222. doi: 10.1093/jimmun/vkae031.
The 2022 Mpox virus (MPXV) outbreak revitalized questions about immunity against MPXV and vaccinia-based vaccines (VAC-V), but studies are limited. We analyzed immunity against MPXV in individuals infected with MPXV or vaccinated with the licensed modified vaccinia Ankara (MVA) Bavarian Nordic or an experimental MVA-HIVB vaccine. The frequency of neutralizing antibody responders was higher among MPXV-infected individuals than MVA vaccinees. Both MVA vaccines induced similar and strong humoral responses. Similarly, we show a higher frequency and magnitude (5-fold) of T cell responses, mainly mediated by CD8+ T cells, against a peptide pool containing selected sequences from MPXV, variola, and VAC-V in MPXV-infected individuals than MVA vaccinees. We describe a hierarchy of cross-reactive T cell responses against 5 peptide pools that are highly homologous between VAC-V and MPXV 2022, with the highest frequency of responders against MVA-121L and MVA-018L proteins. Both vaccines stimulated a notable frequency of polyfunctional CD4+ and CD8+ T cell responses, with a subset of CD4+ T cells showing a mixed cytokine profile. Finally, we found that smallpox vaccination in childhood positively affected humoral but not T cell vaccine responses, whereas these responses were not affected in people living with HIV. These findings contribute to deciphering and monitoring the profile of immunity to MPXV and MVA. In the context of a potential threat of the reemergence of smallpox following bioterrorism, the diversification and availability of potent vaccines is crucial. The comparable immunogenicity of both MVA vaccines emphasizes the potential utility of MVA-HIVB as a valuable new tool for controlling MPXV outbreaks.
2022年猴痘病毒（MPXV）疫情再次引发了关于针对MPXV的免疫力以及基于痘苗的疫苗（VAC-V）的问题，但相关研究有限。我们分析了感染MPXV或接种了已获许可的安卡拉改良痘苗病毒（MVA）巴伐利亚北欧公司疫苗或实验性MVA-HIVB疫苗的个体对MPXV的免疫力。MPXV感染个体中中和抗体应答者的频率高于MVA疫苗接种者。两种MVA疫苗均诱导了相似且强烈的体液反应。同样，我们发现，与MVA疫苗接种者相比，MPXV感染个体针对包含MPXV、天花病毒和VAC-V选定序列的肽库的T细胞反应频率更高且强度更大（高5倍），主要由CD8+T细胞介导。我们描述了针对5个肽库的交叉反应性T细胞反应层次结构，这些肽库在VAC-V和2022年MPXV之间高度同源，对MVA-121L和MVA-018L蛋白的应答者频率最高。两种疫苗均刺激了显著频率的多功能CD4+和CD8+T细胞反应，其中一部分CD4+T细胞表现出混合细胞因子谱。最后，我们发现儿童时期接种天花疫苗对体液免疫有积极影响，但对T细胞疫苗反应没有影响，而这些反应在艾滋病毒感染者中不受影响。这些发现有助于解读和监测对MPXV和MVA的免疫情况。在生物恐怖主义后天花可能重新出现的潜在威胁背景下，有效疫苗的多样化和可及性至关重要。两种MVA疫苗相当的免疫原性强调了MVA-HIVB作为控制MPXV疫情宝贵新工具的潜在效用。
