Type I IFN autoantibodies underlie chikungunya live-attenuated vaccine encephalitis
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®) was developed to address. In 2025, five unrelated adults (aged 82 to 88) on the island of La Réunion (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-α and -ω 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.
Authors
- Julien Jabot
- Y. Yazdanpanah
- Lotfi Dahmane
- A. Gervais
- Cyril Ferdynus (ORCID: https://orcid.org/0000-0003-1502-0672)
- Qian Zhang (ORCID: https://orcid.org/0000-0002-6889-7112)
- Étienne Frumence (ORCID: https://orcid.org/0000-0002-7734-7737)
- Lucy Bizien (ORCID: https://orcid.org/0000-0001-9163-9122)
- Anne Puel
- Radj Cally (ORCID: https://orcid.org/0000-0002-6053-0332)
- M-P Moiton
- Paul Bastard
- Shen-Ying Zhang
- Xavier de Lamballerie
- Marie-Christine Jaffar-Bandjee
- Alexis Maillard
- Jean-Laurent Casanova
- Aurélie Cobat
- Émilie Mosnier
Institutions
- Inserm (FR)
- Université Paris Cité (FR)
- Hospital for Sick Children (CA)
- Centre Hospitalier Universitaire de La Réunion (RE)
- Assistance Publique – Hôpitaux de Paris (FR)
- Laboratoire National de Référence (MA)
- Institut de Médecine Tropicale du Service de Santé des Armées (FR)
- Centre Hospitalier Universitaire de Liège (BE)
- Hôpital Saint-Louis (FR)
- Hôpital Bichat-Claude-Bernard (FR)
- Processus Infectieux en Milieu Insulaire Tropical (RE)
- Institut des Maladies Génétiques Imagine (FR)
- Rockefeller University (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-01-22
- DOI
- https://doi.org/10.1073/pnas.2532212123
- Citations
- 4
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 167.39
Funders
- St. Giles Foundation
- Fondation du Souffle
- Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
- Institut des maladies génétiques Imagine
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fondation pour la Recherche Médicale
- Stavros Niarchos Foundation
- Hospital for Sick Children
- National Institutes of Health
- National Center for Advancing Translational Sciences
- CHIST-ERA