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

Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Virology and Infectious Disease. The Rockefeller University. New York, NY.
Laboratory of Virology and Infectious Disease. The Rockefeller University. New York, NY.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Ministry of Health. Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brazil.
Ministry of Health. Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brazil.
Ministry of Health. Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Laboratory of Immunological Techniques. Rio de Janeiro, RJ, Brazil.
Ministry of Health. Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Laboratory of Immunological Techniques. Rio de Janeiro, RJ, Brazil.
Ministry of Health. Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Rio de Janeiro, RJ, Brazil.
Ministry of Health. Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brazil.
Tropical Medicine Department. Tropenklinik Paul-Lechler-Krankenhaus. Tübingen, Germany.
Tropical Medicine Department. Tropenklinik Paul-Lechler-Krankenhaus. Tübingen, Germany.
Emory Vaccine Center and the Department of Microbiology and Immunology. Emory University School of Medicine. Atlanta, GA. / Institute for Immunity, Transplantation and Infection. Department of Pathology. Department of Microbiology and Immunology. Stanford University. Stanford, CA.
Emory Vaccine Center and the Department of Microbiology and Immunology. Emory University School of Medicine. Atlanta, GA. / Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases. Division of Scientific Resources. Atlanta, GA.
Department of Clinical Sciences. Institute of Tropical Medicine. Antwerp, Belgium.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Clinical Immunology and Microbiology. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France.
Laboratory of Virology. University of Paris. Cochin Hospital. Assistance Publique. Hôpitaux de Paris. Paris, France.
Laboratory of Immunology. University of Paris. Cochin Hospital. Assistance Publique. Hôpitaux de Paris. Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Clinical Immunology and Microbiology. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Clinical Immunology and Microbiology. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD.
Laboratory of Clinical Immunology and Microbiology. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, MD.
Emory Vaccine Center and the Department of Microbiology and Immunology. Emory University School of Medicine. Atlanta, GA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY. / New York Medical College. Valhalla, NY.
St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Virology and Infectious Disease. The Rockefeller University. New York, NY.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY.
Laboratory of Virology and Infectious Disease. The Rockefeller University. New York, NY.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch. Institut National de la Santé et de la Recherche M´edicale. Necker Hospital for Sick Children. Paris, France. / University of Paris. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. The Rockefeller University. New York, NY. / Howard Hughes Medical Institute. New York, NY.

Abstract in Portuguese

A vacina viva atenuada do vírus da febre amarela (YFV) pode, em casos raros, causar doença com risco de vida, geralmente em pacientes sem história prévia de doença viral grave. A deficiência completa de IFNAR1 autossômica recessiva (AR) foi relatada em um paciente de 12 anos de idade. Aqui, nós estudamos sete outros pacientes previamente saudáveis com idades entre 13 e 80 anos com doença inexplicável associada à vacina YFV com risco de vida. Um paciente de 13 anos tinha deficiência completa de IFNAR2 de AR. Três outros pacientes vacinados com idades de 47, 57 e 64 anos apresentaram altos títulos de auto-Abs circulantes contra pelo menos 14 dos 17 IFNs do tipo I individuais. Esses anticorpos foram recentemente demonstrados como subjacentes a pelo menos 10% dos casos de pneumonia COVID-19 com risco de vida. Os auto-Abs foram neutralizantes in vitro, bloqueando o efeito protetor do IFN-α2 contra cepas vacinais de YFV. A deficiência de AR IFNAR1 ou IFNAR2 e auto-Abs neutralizantes contra IFNs do tipo I foram responsáveis por mais da metade dos casos de doença associada à vacina YFV com risco de vida estudados aqui. Indivíduos previamente saudáveis podem ser testados para ambas as predisposições antes da vacinação anti-YFV.

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.

Citation

BASTARD, Paul et al. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. Journal of Experimental Medicine, v. 2018, n. 4, p. 1-16, e20202486, 2021.

DOI

10.1084/jem.20202486

ISSN

0022-1007

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/51336

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