Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory, Cape Town, South Africa.
Nat Commun. 2022 Nov 3;13(1):6594. doi: 10.1038/s41467-022-34061-7.
Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-[Formula: see text]2, TNF-[Formula: see text], CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.
结核病疫苗的研发受到缺乏有效免疫保护相关指标的阻碍。在前瞻性样本中探索疾病和/或感染的免疫相关指标，可以为该领域提供信息。我们研究了先前确定的结核病发病风险的免疫相关指标是否也与接种卡介苗的南非婴儿中结核分枝杆菌感染风险增加有关，这些婴儿在 2-3 年的随访期间感染了结核分枝杆菌。结核分枝杆菌感染的定义是通过定量干扰素释放试验（QuantiFERON test）转为阳性反应来确定的。我们证明了炎症和免疫激活与结核分枝杆菌感染的风险相关。随后感染结核分枝杆菌的婴儿中，Ag85A 特异性 IgG 升高，同时与免疫球蛋白相关基因和 I 型干扰素的上调基因表达相关。随后感染结核分枝杆菌的婴儿的血浆中 IFN-γ2、TNF-α、CXCL10（IP-10）和补体 C2 的水平也更高。
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