Ciabattini Annalisa, Pettini Elena, Fiorino Fabio, Polvere Jacopo, Lucchesi Simone, Coppola Chiara, Costagli Simone, Pastore Gabiria, Sicuranza Anna, Tozzi Monica, Lippi Arianna, Panza Francesca, Bocchia Monica, Bucalossi Alessandro, Garosi Guido, Bennett David, Bernazzali Sonia, Fabbiani Massimiliano, Montagnani Francesca, Medaglini Donata
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
EBioMedicine. 2025 Mar;113:105577. doi: 10.1016/j.ebiom.2025.105577. Epub 2025 Feb 4.
Individuals with primary and secondary immunodeficiencies, being more susceptible to infections, are a priority for vaccination. Here, we determined and compared in a longitudinal study the immune response elicited by SARS-CoV-2 vaccination across different groups of individuals who are immunocompromised.
In the PatoVac_COV longitudinal prospective single-centre study, the spike-specific B cell and antibody responses to SARS-CoV-2 mRNA vaccination were compared across 5 different groups of individuals with haematological malignancies, hematopoietic stem cell (HCT) or solid organ transplantation (SOT), undergoing haemodialysis, and people living with HIV (PLWH), for a total of 585 participants. Data from participants who were immunocompromised were compared to a group of 123 participants who were immunocompetent. Blood samples were collected before and after each vaccine administration, up to 2 years.
A different immune responsiveness was observed after the first two vaccine doses, with haematological, haemodialysis, and SOT participants showing reduced responsiveness compared to HCT and PLWH, and relative to the comparison group. Spike-specific B cell response was both slower and lower in all groups except in PLWH when compared to participants who were immunocompetent. However, the first booster dose enhanced both the B and the antibody responses in all groups, that persisted up to 2 years after the first vaccine administration. The administration of Omicron-adapted booster vaccines promoted a primary BA.2 RBD-specific B cell response, especially in participants who were immunocompromised. Despite repeated vaccinations, a subset of persistent low-responders, especially among SOT, was identified.
Our study highlights the heterogeneous immune response across individuals with different pathologies, the pivotal role of the first booster dose, the primary activation of Omicron-specific B cells elicited by updated variant-adapted vaccines and the persistence of low-responders despite multiple vaccine administrations. These aspects have a clinical relevance for planning vaccination schedules tailored for individuals with different immunocompromising conditions.
This work was supported by funds from the Department of Medical Biotechnologies of the University of Siena, and from EU within the NextGenerationEU-MUR PNRR Tuscany Health Ecosystem (Project no ECS00000017-THE).
原发性和继发性免疫缺陷个体更容易感染，是疫苗接种的重点对象。在此，我们在一项纵向研究中确定并比较了不同免疫功能低下个体群体对SARS-CoV-2疫苗接种产生的免疫反应。
在PatoVac_COV纵向前瞻性单中心研究中，比较了5组不同个体对SARS-CoV-2 mRNA疫苗接种的刺突特异性B细胞和抗体反应，这些个体包括血液系统恶性肿瘤患者、造血干细胞（HCT）或实体器官移植（SOT）受者、接受血液透析者以及艾滋病毒感染者（PLWH），共585名参与者。将免疫功能低下参与者的数据与一组123名免疫功能正常的参与者进行比较。在每次疫苗接种前后采集血样，最长持续2年。
在前两剂疫苗接种后观察到不同的免疫反应性，血液系统疾病患者、接受血液透析者和SOT受者与HCT受者和PLWH相比，以及与对照组相比，反应性降低。与免疫功能正常的参与者相比，除PLWH外，所有组的刺突特异性B细胞反应均较慢且较低。然而，第一剂加强针增强了所有组的B细胞和抗体反应，在首次疫苗接种后持续长达2年。接种针对奥密克戎毒株的加强疫苗促进了主要的BA.2 RBD特异性B细胞反应，尤其是在免疫功能低下的参与者中。尽管多次接种疫苗，但仍发现了一部分持续低反应者，尤其是在SOT受者中。
我们的研究强调了不同病理个体之间免疫反应的异质性、第一剂加强针的关键作用、更新的变异株适配疫苗引发的奥密克戎特异性B细胞的初次激活以及尽管多次接种疫苗仍存在低反应者。这些方面对于为不同免疫功能低下状况的个体制定量身定制的疫苗接种计划具有临床意义。
这项工作得到了锡耶纳大学医学生物技术系的资金支持，以及欧盟在下一代欧盟-复苏与韧性计划托斯卡纳健康生态系统（项目编号ECS00000017-THE）下的资助。
