Type I IFN autoantibodies underlie chikungunya live-attenuated vaccine encephalitis

• 成果类型: Article
• 署名作者: Gervais, Adrian; Bastard, Paul; Zhang, Qian; Jaffar-Bandjee, Marie-Christine; Bizien, Lucy; Dahmane, Lotfi; Moiton, Marie-Pierre; Jabot, Julien; Cally, Radj; Maillard, Alexis; Frumence, Etienne; De Lamballerie, Xavier; Yazdanpanah, Yazdan; Rosain, Jeremie; Cobat, Aurelie; Abel, Laurent; Puel, Anne; Ferdynus, Cyril; Mosnier, Emilie; Gerardin, Patrick; Zhang, Shen-Ying; Casanova, Jean-Laurent
• 署名单位: Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Institut National de la Sante et de la Recherche Medicale (Inserm); Hopital Universitaire Necker-Enfants Malades - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Rockefeller University; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Saint-Louis - APHP; Hopital Universitaire Necker-Enfants Malades - APHP; CHU Reunion; CHU Reunion; CHU Reunion; CHU Reunion; CHU Reunion; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Aix-Marseille Universite; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Bichat-Claude Bernard - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Hopital Universitaire Necker-Enfants Malades - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); CHU Reunion; CHU Reunion; University of La Reunion; Institut National de la Sante et de la Recherche Medicale (Inserm); Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2532212123
• 发表日期: 2026-01-27
• 页码: e2532212123
• 关键词: human autoantibodies; Type; interferons; chikungunya vaccine encephalitis; live-attenuated vaccines; severe covid-19; interferon; patient

摘要

Human autoantibodies neutralizing type I interferons (IFNs) have emerged as strong, common, and global determinants of a growing number of severe viral diseases, including hypoxemic viral pneumonia, arboviral encephalitis, and adverse reaction to the live-attenuated yellow fever virus (YFV) vaccine. Chikungunya virus (CHIKV) is a growing global health concern that the live-attenuated vaccine VLA1553 (IXCHIQ (R)) was developed to address. In 2025, five unrelated adults (aged 82 to 88) on the island of La R & eacute;union (France) developed severe reactions postvaccination; two died. The three patients with encephalitis (aged 84 to 85), including one lethal case, had immunoglobulin G autoantibodies in the blood neutralizing high concentrations of both IFN-alpha and -omega on admission. An 82-y-old survived rhabdomyolysis without encephalitis, and an 88-y-old died during hospitalization following CHIKV infection despite late vaccination; both lacked autoantibodies against type I IFNs. Autoantibodies neutralizing type I IFNs underlie all three cases of live-attenuated CHIKV vaccine encephalitis studied. Individuals with autoantibodies neutralizing type I IFNs should not be inoculated with live-attenuated YFV and CHIKV vaccines.