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.
University of Paris, Imagine Institute, Paris, France.
J Exp Med. 2021 Apr 5;218(4). doi: 10.1084/jem.20202486.
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.
黄热病病毒（YFV）减毒活疫苗在极少数情况下会导致危及生命的疾病，通常发生在没有既往严重病毒感染史的患者中。曾有一名 12 岁的患者被报道存在常染色体隐性（AR）完全 IFNAR1 缺陷。在此，我们研究了另外 7 名此前健康的、年龄在 13 岁至 80 岁之间的、因不明原因发生危及生命的 YFV 疫苗相关疾病的患者。其中 1 名 13 岁的患者存在 AR 完全 IFNAR2 缺陷。另外 3 名分别在 47、57 和 64 岁接种疫苗的患者，其循环中针对至少 17 种 I 型 IFNs 中的 14 种的自身抗体滴度较高。这些抗体最近被证明是导致至少 10%的 COVID-19 肺炎重症病例的原因之一。这些自身抗体在体外具有中和作用，阻断了 IFN-α2 对 YFV 疫苗株的保护作用。因此，AR IFNAR1 或 IFNAR2 缺陷以及针对 I 型 IFNs 的中和自身抗体，解释了我们在此研究的危及生命的 YFV 疫苗相关疾病的一半以上病例。在接种抗 YFV 疫苗之前，可对既往健康的受试者进行这两种易感性的检测。
