Lee Jenny M, Sachithanandham Jaiprasath, Lee John S, Shapiro Janna R, Li Maggie, Sitaris Ioannis, Peralta Stephanie R, Wouters Camille, Cox Andrea L, Segev Dorry L, Durand Christine M, Robien Mark, Tobian Aaron A R, Karaba Andrew H, Blankson Joel N, Werbel William A, Pekosz Andrew, Klein Sabra L
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
bioRxiv. 2024 Sep 3:2024.09.01.610689. doi: 10.1101/2024.09.01.610689.
Solid organ transplant recipients (SOTRs) suffer more frequent and more severe infections due to their compromised immune responses resulting from immunosuppressive treatments designed to prevent organ rejection. Pharmacological immunosuppression can adversely affect immune responses to vaccination. A cohort of kidney transplant recipients (KTRs) received their third dose of ancestral, monovalent COVID-19 vaccine in the context of a clinical trial and antibody responses to the vaccine strain, as well as to Omicron variants BA.1 and BA.5 were investigated and compared with healthy controls. Total IgG and live virus neutralizing antibody titers were reduced in KTRs compared to controls for all variants. KTRs displayed altered IgG subclass switching, with significantly lower IgG3 antibodies. Responses in KTRs were also very heterogeneous, with some individuals showing strong responses but a significant number showing no Omicron-specific neutralizing antibodies. Taken together, immune responses after COVID-19 vaccination in KTRs were not only lower than healthy controls but highly variable, indicating that simply increasing the number of vaccine doses alone may not be sufficient to provide greater protection in this population.
This study addresses the challenges faced by kidney transplant recipients (KTRs) in mounting effective immune responses against COVID-19. By evaluating the antibody responses to a third dose of monovalent mRNA COVID-19 vaccine and its effectiveness against Omicron subvariants (BA.1 and BA.5), this study reveals significant reductions in both binding and neutralizing antibodies in KTRs compared to healthy controls. The research highlights altered IgG subclass switching and heterogeneous responses within the KTR population. Reduced recognition of variants, coupled with differences in IgG subclasses, decreases both the quality and quantity of protective antibodies after vaccination in KTRs. These findings underscore the need for tailored vaccination strategies for immunosuppressed populations such as KTRs. Alternative formulations and doses of COVID-19 vaccines should be considered for people with severely compromised immune systems, as more frequent vaccinations may not significantly improve the response, especially regarding neutralizing antibodies.
实体器官移植受者（SOTR）由于旨在预防器官排斥的免疫抑制治疗导致免疫反应受损，因而遭受更频繁、更严重的感染。药物免疫抑制会对疫苗接种的免疫反应产生不利影响。一组肾移植受者（KTR）在一项临床试验中接种了第三剂原始单价新冠疫苗，并对其针对疫苗毒株以及奥密克戎变种BA.1和BA.5的抗体反应进行了研究，并与健康对照进行比较。与对照组相比，KTR对所有变种的总IgG和活病毒中和抗体滴度均降低。KTR表现出IgG亚类转换改变，IgG3抗体显著降低。KTR中的反应也非常不均一，一些个体表现出强烈反应，但相当数量的个体未显示出奥密克戎特异性中和抗体。总体而言，KTR接种新冠疫苗后的免疫反应不仅低于健康对照，而且高度可变，这表明仅增加疫苗剂量可能不足以在该人群中提供更大的保护。
本研究解决了肾移植受者（KTR）在产生针对新冠病毒的有效免疫反应方面面临的挑战。通过评估对第三剂单价mRNA新冠疫苗的抗体反应及其对奥密克戎亚变种（BA.1和BA.5）的有效性，本研究揭示与健康对照相比，KTR的结合抗体和中和抗体均显著降低。该研究突出了KTR群体中IgG亚类转换改变和反应不均一的情况。对变种的识别减少，再加上IgG亚类的差异，降低了KTR接种疫苗后保护性抗体的质量和数量。这些发现强调了为KTR等免疫抑制人群制定量身定制的疫苗接种策略的必要性。对于免疫系统严重受损的人群，应考虑使用替代配方和剂量的新冠疫苗，因为更频繁的接种可能不会显著改善反应，尤其是在中和抗体方面。
