Auto-Antibodies to Type I IFNs Can Underlie Adverse Reactions to Yellow Fever Live Attenuated Vaccine

Authors

Paul Bastard
Stephen J. Seligman, New York Medical CollegeFollow
Jean-Laurent Casanova

Author Type(s)

Faculty

DOI

10.1084/jem.20202486

Journal Title

The Journal of Experimental Medicine

First Page

20202486

Last Page

20202486

Document Type

Article

Publication Date

4-5-2021

Department

Pathology, Microbiology and Immunology

Keywords

Adolescent, Adult, Aged, Antibodies, Neutralizing, Autoantibodies, Autoimmune Diseases, COVID-19, Female, Genetic Diseases, Inborn, HEK293 Cells, Humans, Interferon-alpha, Male, Middle Aged, Receptor, Interferon alpha-beta, SARS-CoV-2, Vaccines, Attenuated, Yellow Fever Vaccine, Yellow fever virus

Disciplines

Medicine and Health Sciences

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.

Comments

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Recommended Citation

Bastard, P., Seligman, S., & Casanova, J. (2021). Auto-Antibodies to Type I IFNs Can Underlie Adverse Reactions to Yellow Fever Live Attenuated Vaccine. The Journal of Experimental Medicine, 218 (4), 20202486-20202486. https://doi.org/10.1084/jem.20202486