Type I IFN autoantibodies underlie chikungunya live-attenuated vaccine encephalitis
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (22)
Adrian Gervais
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children
Paul Bastard
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children
Qian Zhang
Marie-Christine Jaffar-Bandjee
Associated National Reference Center for Arboviruses, Centre Hospitalier Universitaire-Réunion
Lucy Bizien
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children
Lotfi Dahmane
Service de Maladies infectieuses, Centre Hospitalier Universitaire Félix Guyon
Marie-Pierre Moiton
Service de Maladies infectieuses, Centre Hospitalier Universitaire Félix Guyon
Julien Jabot
Intensive Care Unit, Centre Hospitalier Universitaire
Radj Cally
Department of Intensive Care Medicine, Felix Guyon University Hospital
Alexis Maillard
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children
Etienne Frumence
Associated National Reference Center for Arboviruses, Centre Hospitalier Universitaire-Réunion
Xavier de Lamballerie
Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, Institut de recherche pour le developpement 190, Inserm 1207, Institut de recherche biomédicale des armées)
Yazdan Yazdanpanah
Department of Infectious Diseases, Bichat-Claude Bernard Hospital
Jérémie Rosain
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children
Aurélie Cobat
St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University
Laurent Abel
St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University
Anne Puel
Cyril Ferdynus
Centre for Clinical Investigation Clinical Epidemiology (INSERM CIC 1410), Centre Hospitalier Universitaire de La Réunion
Émilie Mosnier
Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de La Réunion Sites Sud
Patrick Gérardin
Centre for Clinical Investigation Clinical Epidemiology (INSERM CIC 1410), Centre Hospitalier Universitaire de La Réunion
Shen-Ying Zhang
St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University
Jean-Laurent Casanova