PDF(Pubmed)
Abstract：
UNASSIGNED: Comirnaty, Pfizer-BioNTech\'s polyethylene-glycol (PEG)-containing Covid-19 vaccine, can cause hypersensitivity reactions (HSRs), or rarely, life-threatening anaphylaxis in a small fraction of immunized people. A causal role of anti-PEG antibodies (Abs) has been proposed, but causality has not yet proven in an animal model. The aim of this study was to provide such evidence using pigs immunized against PEG, which displayed very high levels of anti-PEG antibodies (Abs). We also aimed to find evidence for a role of complement activation and thromboxane A2 release in blood to explore the mechanism of anaphylaxis.
UNASSIGNED: Pigs (n = 6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v., and the rise of anti-PEG IgG and IgM were measured in serial blood samples with ELISA. After ∼2-3 weeks the animals were injected i.v. with 1/3 human dose of the PEGylated mRNA vaccine, Comirnaty, and the hemodynamic (PAP, SAP) cardiopulmonary (HR, EtCO2,), hematological (WBC, granulocyte, lymphocyte and platelet counts) parameters and blood immune mediators (anti-PEG IgM and IgG antibodies, thromboxane B2, C3a) were measured as endpoints of HSRs (anaphylaxis).
UNASSIGNED: The level of anti-PEG IgM and IgG rose 5-10-thousand-fold in all of 6 pigs immunized with Doxebo by day 6, after which time all animals developed anaphylactic shock to i.v. injection of 1/3 human dose of Comirnaty. The reaction, starting within 1 min involved maximal pulmonary hypertension and decreased systemic pulse pressure amplitude, tachycardia, granulo- and thrombocytopenia, and skin reactions (flushing or rash). These physiological changes or their absence were paralleled by C3a and TXB2 rises in blood.
UNASSIGNED: Consistent with previous studies, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty, which involves complement activation, and, hence, it represents C activation-related pseudo-anaphylaxis. The setup provides the first large-animal model for mRNA-vaccine-induced anaphylaxis in humans.
UNASSIGNED: Pigs (n = 6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v., and the rise of anti-PEG IgG and IgM were measured in serial blood samples with ELISA. After ∼2-3 weeks the animals were injected i.v. with 1/3 human dose of the PEGylated mRNA vaccine, Comirnaty, and the hemodynamic (PAP, SAP) cardiopulmonary (HR, EtCO2,), hematological (WBC, granulocyte, lymphocyte and platelet counts) parameters and blood immune mediators (anti-PEG IgM and IgG antibodies, thromboxane B2, C3a) were measured as endpoints of HSRs (anaphylaxis).
UNASSIGNED: The level of anti-PEG IgM and IgG rose 5-10-thousand-fold in all of 6 pigs immunized with Doxebo by day 6, after which time all animals developed anaphylactic shock to i.v. injection of 1/3 human dose of Comirnaty. The reaction, starting within 1 min involved maximal pulmonary hypertension and decreased systemic pulse pressure amplitude, tachycardia, granulo- and thrombocytopenia, and skin reactions (flushing or rash). These physiological changes or their absence were paralleled by C3a and TXB2 rises in blood.
UNASSIGNED: Consistent with previous studies, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty, which involves complement activation, and, hence, it represents C activation-related pseudo-anaphylaxis. The setup provides the first large-animal model for mRNA-vaccine-induced anaphylaxis in humans.
摘要：
■Comirnaty,Pfizer-BioNTech的含聚乙二醇（PEG）的Covid-19疫苗，可引起过敏反应（HSR），或者很少，在一小部分免疫人群中危及生命的过敏反应。已经提出了抗PEG抗体（Abs）的因果作用，但是因果关系尚未在动物模型中得到证实。这项研究的目的是使用免疫接种PEG的猪提供这样的证据，其显示非常高水平的抗PEG抗体(Ab)。我们还旨在寻找血液中补体激活和血栓素A2释放的作用的证据，以探索过敏反应的机制。
■用0.1mg/kg聚乙二醇化脂质体（Doxebo）静脉注射免疫猪（n=6），用ELISA法检测系列血样中抗PEGIgG和IgM的升高。2-3周后，将动物静脉注射1/3人剂量的聚乙二醇化mRNA疫苗，Comirnaty,和血液动力学（PAP，SAP)心肺(HR，EtCO2,),血液学（WBC，粒细胞,淋巴细胞和血小板计数）参数和血液免疫介质（抗PEGIgM和IgG抗体，血栓素B2，C3a）作为HSR（过敏反应）的终点。
■在第6天用Doxebo免疫的所有6头猪中，抗PEGIgM和IgG的水平上升了5-1万倍，此后所有动物在静脉内发生过敏性休克。注射1/3人剂量的Comirnaty。反应,在1分钟内开始涉及最大肺动脉高压和降低的全身脉压幅度，心动过速,颗粒和血小板减少症，和皮肤反应（潮红或皮疹）。这些生理变化或它们的缺失与血液中C3a和TXB2的升高平行。
■与以前的研究一致，这些数据显示了抗PEGAb在对Comirnaty的过敏反应中的因果作用，涉及补体激活，and,因此，它代表C激活相关的假性过敏反应。该设置提供了第一个用于人类mRNA疫苗诱导的过敏反应的大型动物模型。
■用0.1mg/kg聚乙二醇化脂质体（Doxebo）静脉注射免疫猪（n=6），用ELISA法检测系列血样中抗PEGIgG和IgM的升高。2-3周后，将动物静脉注射1/3人剂量的聚乙二醇化mRNA疫苗，Comirnaty,和血液动力学（PAP，SAP)心肺(HR，EtCO2,),血液学（WBC，粒细胞,淋巴细胞和血小板计数）参数和血液免疫介质（抗PEGIgM和IgG抗体，血栓素B2，C3a）作为HSR（过敏反应）的终点。
■在第6天用Doxebo免疫的所有6头猪中，抗PEGIgM和IgG的水平上升了5-1万倍，此后所有动物在静脉内发生过敏性休克。注射1/3人剂量的Comirnaty。反应,在1分钟内开始涉及最大肺动脉高压和降低的全身脉压幅度，心动过速,颗粒和血小板减少症，和皮肤反应（潮红或皮疹）。这些生理变化或它们的缺失与血液中C3a和TXB2的升高平行。
■与以前的研究一致，这些数据显示了抗PEGAb在对Comirnaty的过敏反应中的因果作用，涉及补体激活，and,因此，它代表C激活相关的假性过敏反应。该设置提供了第一个用于人类mRNA疫苗诱导的过敏反应的大型动物模型。
