Bivalent COVID-19 Vaccines: Can the Original Antigenic Sin Be Forgiven?
Bivalent COVID-19 Vaccines: Can the Original Antigenic Sin Be Forgiven?
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二价COVID-19疫苗：抗原原罪可以被原谅吗？
DOI：
10.1093/infdis/jiad073
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Blankson,JoelN
中科院分区：
文献类型：
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作者：
Blankson,JoelN
于二零二二年八月三十一日，美国（美国）食品及药物管理局批准Moderna及Pfizer-BioNTech 2019冠状病毒病（COVID-19）疫苗的二价制剂[1]。这些修饰的疫苗含有编码祖先WA 1/2020和Omicron BA的信使RNA（mRNA）。4/BA。5种刺突蛋白。希望他们能给广管局提供豁免权。5病毒，其与WA 1/2020的不同之处在于刺突蛋白中的> 30个突变，并且是当时循环中的主要变体。不幸的是，研究表明BA的中和抗体水平。在接受二价疫苗的患者中，5种变异体的感染率并不显著高于接受带有WA 1/2020 mRNA的单价疫苗的患者[2，3]。换句话说，接种BA疫苗。5刺突蛋白没有导致明显更好的抗体应答。这个令人失望的结果的原因还没有确定，但抗原印迹，也被称为“原始抗原罪”，已被援引为这些结果的一个潜在原因。虽然有一些值得注意的例外[4]，广泛的基因片段重组过程导致产生不同的T细胞和B细胞受体，这些受体应该能够识别我们将遇到的几乎任何可能的病原体。缺点是，具有任何给定受体的细胞很少，因此当我们第一次看到病原体时，具有病原体抗原特异性受体的幼稚细胞必须广泛增殖，然后我们才能建立有效的初级适应性免疫反应。这些幼稚细胞中的一些将成为记忆细胞，以更高的水平循环，以便如果再次遇到相同的抗原，将发生更快，更有效的二次适应性免疫反应。当我们遇到一种病原体上的抗原与我们以前遇到的抗原相似时，就会发生最初的抗原罪[5，6]。据认为，不是在具有对新抗原的高亲和力受体的罕见幼稚淋巴细胞增殖的情况下启动初级免疫应答，而是在具有对原始抗原和新抗原都具有交叉反应性的受体的记忆细胞被刺激的情况下发生次级应答。如果2种病原体的靶向表位相同或非常相似，这可能是有利的，因为这样2种表位将被同等地识别。然而，在许多情况下，由于交叉反应性存储器单元
On 31 August 2022, the United States (US) Food and Drug Administration authorized bivalent formulations of the Moderna and Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccines [1]. These modified vaccines contain messenger RNA (mRNA) encoding for both the ancestral WA1/2020 and the Omicron BA. 4/BA. 5 spike proteins. The hope was that they would provide immunity to the BA. 5 virus, which differs from WA1/2020 by> 30 mutations in the spike protein and was the predominant variant in circulation at the time. Unfortunately, studies have shown that the levels of neutralizing antibodies to the BA. 5 variant were not significantly higher in patients who received the bivalent vaccine than those who received the monovalent vaccine with WA1/2020 mRNA [2, 3]. In other words, vaccination with BA. 5 spike protein did not lead to an appreciably better antibody response. The reason for this disappointing result has not yet been determined, but antigenic imprinting, also known as the “original antigenic sin,” has been invoked as a potential cause for these results.To fully explain this tenant of immunotheology, one has to review some basic principles. While there are some notable exceptions [4], the process of extensive gene segment recombination leads to the production of diverse T-and B-cell receptors that should be capable of recognizing almost any conceivable pathogen we will ever encounter. The drawback is that there are very few cells with any given receptor and so when we first see a pathogen, naive cells with receptors specific for the pathogen’s antigens have to proliferate extensively before we can mount an effective primary adaptive immune response. Some of these naive cells will become memory cells that circulate at higher levels so that if the same antigen is encountered again, a faster, more effective secondary adaptive immune response will occur. The original antigenic sin occurs when we encounter antigens on a pathogen that is similar to one we have previously encountered [5, 6]. It is thought that rather than initiating a primary immune response where rare naive lymphocytes that have high-affinity receptors for the new antigens proliferate, a secondary response occurs where memory cells with receptors that are cross-reactive for both the original and new antigens are stimulated. This could potentially be advantageous if the targeted epitopes of the 2 pathogens are identical or very similar because then the 2 epitopes will be equally recognized. However, in many cases, because the cross-reactive memory cells