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

TitleAuto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine.
Publication TypeJournal Article
Year of Publication2021
AuthorsBastard, P, Michailidis, E, Hoffmann, H-H, Chbihi, M, Le Voyer, T, Rosain, J, Philippot, Q, Seeleuthner, Y, Gervais, A, Materna, M, de Oliveira, PMouta Nune, Maia, Mde Lourdes, Bom, APaula Dini, Azamor, T, da Conceição, DAraújo, Goudouris, E, Homma, A, Slesak, G, Schäfer, J, Pulendran, B, Miller, JD, Huits, R, Yang, R, Rosen, LB, Bizien, L, Lorenzo, L, Chrabieh, M, Erazo, LV, Rozenberg, F, Jeljeli, MMaxime, Béziat, V, Holland, SM, Cobat, A, Notarangelo, LD, Su, HC, Ahmed, R, Puel, A, Zhang, S-Y, Abel, L, Seligman, SJ, Zhang, Q, MacDonald, MR, Jouanguy, E, Rice, CM, Casanova, J-L
JournalJ Exp Med
Date Published2021 04 05
KeywordsAdolescent, 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

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.

Alternate JournalJ Exp Med
PubMed ID33544838
PubMed Central IDPMC7871457
Grant ListR38 AI140299 / AI / NIAID NIH HHS / United States
U19 AI090023 / AI / NIAID NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
U19 AI057266 / AI / NIAID NIH HHS / United States
R01 AI088364 / AI / NIAID NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
R01 AI124690 / AI / NIAID NIH HHS / United States