肾移植受者感染奥密克戎或接种奥密克戎BA.4/5疫苗后对SARS-CoV-2刺突蛋白免疫反应的比较。
Comparison of immune responses to SARS-CoV-2 spike following Omicron infection or Omicron BA.4/5 vaccination in kidney transplant recipients.
作者信息
Tometten Inga, Brandt Tobias, Schlotz Maike, Stumpf Ricarda, Landmann Sinje, Kantauskaite Marta, Lamberti Joshua, Hillebrandt Jonas, Müller Lisa, Kittel Margarethe, Ivens Katrin, Gruell Henning, Voges Anja, Schaal Heiner, Lübke Nadine, Königshausen Eva, Rump Lars Christian, Klein Florian, Stegbauer Johannes, Timm Jörg
机构信息
Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Department of Nephrology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
出版信息
Front Immunol. 2025 Jan 14;15:1476294. doi: 10.3389/fimmu.2024.1476294. eCollection 2024.
BACKGROUND
The emergence of novel SARS-CoV-2 variants challenges immunity, particularly among immunocompromised kidney transplant recipients (KTRs). To address this, vaccines have been adjusted to circulating variants. Despite intensive vaccination efforts, SARS-CoV-2 infections surged among KTRs during the Omicron wave, enabling a direct comparison of variant-specific immunity following-vaccination against Omicron BA.4/5 or Omicron infection in KTRs.
METHODS
98 SARS-CoV-2 naïve KTRs who had received four vaccine doses were studied. Before and after a 5th antigen exposure, either via the bivalent vaccine composed of ancestral SARS-CoV-2 and Omicron BA.4/5 (29 KTRs) or via natural infection with Omicron (38 BA.4/5, 31 BA.1/2), spike-specific T cells were quantified using Elispot and serum pseudovirus neutralizing activity was assessed against the ancestral Wuhan strain, BA.5 and XBB.1.5.
RESULTS
Compared to BA.4/5 vaccination, spike-specific T-cell responses and neutralization activity were higher up to six months post-Omicron infection and reached levels similar to healthy controls. Vaccinated KTRs showed modestly boosted neutralization activity against the Wuhan strain and BA.5, but not XBB.1.5. Baseline immunity correlated with immune responses three months post-vaccination and post-infection, indicating a predictive value for peak immune responses. Tixagevimab/Cilgavimab treatment was associated with robust neutralization of the Wuhan strain, but ineffective against XBB.1.5.
CONCLUSION
The BA.4/5 vaccine improved neutralizing activity against the BA.4/5 variant, but not against the subsequently circulating XBB.1.5 variant in KTRs. Conversely, omicron infection boosted T cells and humoral responses more effectively, showing efficacy against XBB.1.5. These findings suggest that infection-induced immunity associates with greater protection than vaccination against future variants in KTRs.
背景
新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现对免疫力构成挑战，在免疫功能低下的肾移植受者（KTRs）中尤为如此。为应对这一情况，疫苗已针对流行变体进行了调整。尽管进行了密集的疫苗接种工作，但在奥密克戎毒株流行期间，KTRs中的SARS-CoV-2感染激增，从而能够直接比较接种疫苗后针对奥密克戎BA.4/5或奥密克戎感染的变体特异性免疫力。
方法
对98名未感染过SARS-CoV-2且已接种四剂疫苗的KTRs进行了研究。在第5次抗原暴露前后，通过由原始SARS-CoV-2和奥密克戎BA.4/5组成的二价疫苗（29名KTRs）或通过奥密克戎自然感染（38名BA.4/5、31名BA.1/2），使用酶联免疫斑点法（Elispot）对刺突特异性T细胞进行定量，并评估血清对原始武汉毒株、BA.5和XBB.1.5的假病毒中和活性。
结果
与接种BA.4/5疫苗相比，奥密克戎感染后长达六个月，刺突特异性T细胞反应和中和活性更高，并达到了与健康对照相似的水平。接种疫苗的KTRs对武汉毒株和BA.5的中和活性有适度增强，但对XBB.1.5没有增强。基线免疫力与接种疫苗和感染后三个月的免疫反应相关，表明对峰值免疫反应具有预测价值。替沙格韦单抗/西加韦单抗治疗与对武汉毒株的强效中和相关，但对XBB.1.5无效。
结论
BA.4/5疫苗提高了对BA.4/5变体的中和活性，但对KTRs中随后流行的XBB.1.5变体无效。相反，奥密克戎感染更有效地增强了T细胞和体液反应，显示出对XBB.1.5的效力。这些发现表明，在KTRs中，感染诱导的免疫力比针对未来变体的疫苗接种提供了更强的保护。
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