Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine

Author:

Bastard Paul123ORCID,Michailidis Eleftherios4ORCID,Hoffmann Hans-Heinrich4ORCID,Chbihi Marwa12ORCID,Le Voyer Tom12ORCID,Rosain Jérémie12ORCID,Philippot Quentin12ORCID,Seeleuthner Yoann1ORCID,Gervais Adrian12ORCID,Materna Marie12ORCID,de Oliveira Patricia Mouta Nunes5ORCID,Maia Maria de Lourdes S.5ORCID,Dinis Ano Bom Ana Paula6ORCID,Azamor Tamiris6ORCID,Araújo da Conceição Deborah5ORCID,Goudouris Ekaterini7ORCID,Homma Akira5ORCID,Slesak Günther8ORCID,Schäfer Johannes8ORCID,Pulendran Bali910ORCID,Miller Joseph D.911ORCID,Huits Ralph12ORCID,Yang Rui3ORCID,Rosen Lindsey B.13ORCID,Bizien Lucy12ORCID,Lorenzo Lazaro12ORCID,Chrabieh Maya12ORCID,Erazo Lucia V.1ORCID,Rozenberg Flore14ORCID,Jeljeli Mohamed Maxime15ORCID,Béziat Vivien123ORCID,Holland Steven M.13ORCID,Cobat Aurélie13ORCID,Notarangelo Luigi D.13ORCID,Su Helen C.13ORCID,Ahmed Rafi9ORCID,Puel Anne123ORCID,Zhang Shen-Ying123ORCID,Abel Laurent123ORCID,Seligman Stephen J.316ORCID,Zhang Qian3ORCID,MacDonald Margaret R.4ORCID,Jouanguy Emmanuelle123ORCID,Rice Charles M.4ORCID,Casanova Jean-Laurent12317ORCID

Affiliation:

1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France

2. University of Paris, Imagine Institute, Paris, France

3. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY

4. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY

5. Bio-Manguinhos, Fiocruz, Ministry of Health, Rio de Janeiro, Brazil

6. Laboratory of Immunological Techniques, Bio-Manguinhos, Fiocruz, Ministry of Health, Rio de Janeiro, Brazil

7. Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

8. Tropical Medicine Department, Tropenklinik Paul-Lechler-Krankenhaus, Tübingen, Germany

9. Emory Vaccine Center and the Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA

10. Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA

11. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Scientific Resources, Atlanta, GA

12. Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium

13. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

14. Laboratory of Virology, University of Paris, Cochin Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France

15. Laboratory of Immunology, University of Paris, Cochin Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France

16. New York Medical College, Valhalla, NY

17. Howard Hughes Medical Institute, New York, NY

Abstract

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine–associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.

Funder

Howard Hughes Medical Institute

The Rockefeller University

St. Giles Foundation

National Institutes of Health

National Center for Advancing Translational Sciences

Emergent Ventures

George Mason University

Yale Center for Mendelian Genomics

National Human Genome Research Institute

French National Research Agency

Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence

French Foundation for Medical Research

ANRS-COV05

Square Foundation

Grandir–Fonds de Solidarité pour l’Enfance

SCOR Corporate Foundation for Science

Institut National de la Santé et de la Recherche Médicale

University of Paris

National Institute of Allergy and Infectious Diseases

Imagine Institute

Fondation Bettencourt Schueller

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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