Thygesen Miriam Viktov, Strandhave Charlotte, Kiib Jeanette Mølgaard, Berg Randi, Andersen Malene Söth, Dall Emma Berggren, Hornstrup Bodil Gade, Østergaard Hans Christian, Mose Frank Holden, Gregersen Jon Waarst, Jensen-Fangel Søren, Bech Jesper Nørgaard, Birn Henrik, Thomsen Marianne Kragh, Offersen Rasmus
Department of Clinical Microbiology, Aarhus University Hospital, 8200 Aarhus, Denmark.
Department of Medicine, Gødstrup Hospital, 7400 Herning, Denmark.
Vaccines (Basel). 2025 Jul 22;13(8):777. doi: 10.3390/vaccines13080777.
Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined.
A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages.
After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection.
A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population.
与普通人群相比，肾移植受者（KTRs）对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗的免疫反应显著减弱，主要原因是持续进行免疫抑制治疗。本研究评估了第三剂SARS-CoV-2 mRNA疫苗在KTRs中的免疫原性，并评估了抗体反应与预防SARS-CoV-2突破性感染之间的关联。此外，还检查了接种疫苗后SARS-CoV-2感染的临床和免疫相关性。
135名KTRs的前瞻性队列在第二剂疫苗接种后约六个月接受了第三剂疫苗。在基线（接种前）、第二剂疫苗接种后六个月和第三剂疫苗接种后六周采集血浆样本。使用针对野生型（WT）和病毒株（包括多个奥密克戎亚谱系）的SARS-CoV-2特异性免疫球蛋白G（IgG）滴度和病毒中和试验评估体液反应。
在接种第三剂疫苗后，74%的KTRs检测到SARS-CoV-2特异性IgG抗体，而在接种第二剂疫苗后这一比例为48%。加强免疫后平均IgG滴度增加了约10倍。尽管有这种增加，但针对奥密克戎变体的中和活性仍显著低于针对WT毒株的中和活性。随后发生SARS-CoV-2突破性感染的KTRs在所有测试变体中均表现出中和抗体活性降低。此外，与接受双重或单一疗法的患者相比，接受三联免疫抑制治疗的个体发生SARS-CoV-2突破性感染的风险显著更高。多变量机器学习分析确定年龄以及针对WT、德尔塔和奥密克戎BA.2的中和活性是SARS-CoV-2突破性感染最有力的相关因素。
第三剂SARS-CoV-2 mRNA疫苗显著提高了KTRs中SARS-CoV-2特异性IgG水平；然而，针对奥密克戎变体的中和反应仍然不理想。中和能力减弱和强化免疫抑制是这一免疫受损人群中SARS-CoV-2突破性感染的关键决定因素。
