Current advances in HIV vaccine preclinical studies using Macaque models

The macaque simian or simian/human immunodeficiency virus (SIV/SHIV) challenge model has been widely used to inform and guide human vaccine trials. Substantial advances have been made recently in the application of repeated-low-dose challenge (RLD) approach to assess SIV/SHIV vaccine efficacies (VE). Some candidate HIV vaccines have shown protective effects in preclinical studies using the macaque SIV/SHIV model but the model’s true predictive value for screening potential HIV vaccine candidates needs to be evaluated further. Here, we review key parameters used in the RLD approach and discuss their relevance for evaluating VE to improve preclinical studies of candidate HIV vaccines.     

牛奶相关症状评分在婴儿牛奶蛋白过敏早期识别中的评价：多中心调查分析

目的评价牛奶相关症状评分(CoMiSS)在早期识别婴儿牛奶蛋白过敏(CMPA)中的作用。方法 2016年6月至2017年5月对6家儿科门诊疑似CMPA的210例婴儿进行CoMiSS评分,通过开放性食物激发试验(OFC)明确或排除CMPA诊断。同期选取96例健康体检婴儿为对照组。通过ROC曲线评估CoMiSS识别CMPA的灵敏度和特异度,评价其在早期识别婴儿CMPA中的作用。结果 210例疑似CMPA婴儿中,男114例、女96例,中位年龄4.5个月(1～12个月);其中82例确诊CMPA,中位CoMiSS为7.0分(6.0～8.3分);128例非CMPA婴儿的中位CoMiSS为4.0分(3.0～5.0分)。96例对照组中,男42例、女54例,中位年龄4.1个月(1～12个月);中位CoMiSS为 3.0分(2.0～4.0分)。三组间CoMiSS差异有统计学意义(H=152.58,P0.01)。CoMiSS的ROC曲线下面积(AUC)为0.90,最佳诊断界值为5.5,灵敏度为87.8%,特异度为78.1%。结论 CoMiSS评分临床可操作性强,适合儿科推广。建议以CoMiSS≥6分作为早期识别CMPA标准。     

Yogurt is tolerated by the majority of children with IgE-mediated cow's milk allergy

BackgroundChildren with IgE-mediated cow's milk allergy (IgE-CMA) with gastrointestinal symptoms tolerate yogurt at 100%. Yogurt tolerance in children with IgE-CMA with urticaria and anaphylaxis was 7%.MethodsWe enrolled children with IgE-CMA with cutaneous, respiratory, gastrointestinal and anaphylactic symptoms. All performed prick by prick (PbP) and oral food challenge (OFC) with yogurt. Some children performed also an OFC with CM mixed with wheat flour and baked, baked liquid CM, parmesan.Results34 children were enrolled, 31/34 (91%) with systemic adverse reaction after ingestion of CM (systemic CMA), 3/34 (9%) with isolated contact urticaria (ICU CMA). PbP with yogurt was negative only in one patient. OFC with yogurt was passed (that is, the OFC was negative) by 20/31 (64%) of the children with systemic CMA. 10/11 (91%) of the patients who failed OFC (that is, the OFC was positive) with yogurt were positive to SPT with casein vs. 8/20 (40%) of the patients who passed it (p = 0.018). None of the 19 children who passed OFC with yogurt failed all OFC with processed CM forms other than yogurt that tested vs. 4/8 among those who failed OFC with yogurt (p = 0.006). The rub test with yogurt was negative in 1/3 (33%) of the patients with ICU CMA.ConclusionsThe results of our study are placed alongside others already present in the literature and concerning other methods of processing CM proteins and help to reduce the dietary restrictions of the majority of children with systemic IgE-CMA.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.