Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID)

尽管疫苗技术和治疗干预措施取得了强劲进展，但新冠肺炎大流行继续通过与疾病相关的发病率/死亡率及其对经济稳定和增长的影响来影响我们的世界。癌症患者(特别是那些接受主动免疫抑制或改变治疗的患者)是一个高度脆弱的人群，尽管接种了基因疫苗和加强了基因疫苗，但他们患SARS-CoV2突破性感染和严重新冠肺炎的风险增加。识别高危人群并制定针对严重新冠肺炎的更有效的保护策略至关重要。我们和其他人已经确定了癌症患者的抗体和T细胞反应，并确定癌症治疗(类型和时机)与低于平均水平的疫苗反应密切相关。值得注意的是，与实体肿瘤患者相比，接受血液系统恶性肿瘤治疗的患者免疫功能受损的可能性更大。此外，虽然加强免疫可以恢复某些人的免疫缺陷，但许多癌症患者在疫苗介导的抗体和/或T细胞反应方面仍然存在缺陷。然而，大多数加强后研究没有评估长期持久免疫，也没有表征抗体或T细胞记忆反应。我们假设，实体肿瘤和血液病患者加强免疫后T细胞和抗体反应的持久性和记忆性的变化将主要受治疗类型和时间的影响。这一假设得到了我们评估加强免疫后早期免疫反应的出版物的支持，然而，这里提出的研究将使我们能够在加强免疫后一年检测T细胞和抗体记忆。此外，通过跟踪个体癌症患者的克隆性T细胞群体和表位特异性抗体反应，我们假设可以确定驱动SARS-CoV2基因启动子反应异质性的关键参数。我们将使用俄亥俄州立大学综合癌症中心的新冠肺炎感染和免疫反应疫苗研究(SIIREN)收集的样本进行深入的免疫学研究，以解决我们的假设。

Despite robust advances in vaccine technology and therapeutic intervention, the COVID-19 pandemic continues to impact our world both through disease-associated morbidity/mortality and its influence on economic stability and growth. Cancer patients (especially those receiving active immune suppressive or altering therapy) represent a highly vulnerable population with increased risk of SARS-CoV2 breakthrough infection and severe COVID-19 despite mRNA vaccination and booster. Identifying atrisk individuals and developing more effective protective strategies against severe COVID-19 is of paramount importance. We and others have characterized antibody and T cell responses in cancer patients and identified cancer treatment (type and timing) as critically associated with subpar vaccine responses. Notably, patients being treated for hematological malignancies have greater likelihood of impaired immunity compared with those with solid tumor malignancies. Furthermore, while booster immunization can recover deficiencies in immunity in some individuals, many cancer patients continue to have deficiencies in vaccine-mediated antibody and/or T cell responses. However, most post-booster studies have not assessed long-term durable immunity and have not characterized antibody or T cell memory responses. We hypothesize that variability in the durability and memory of T cell and antibody responses following booster immunization in solid tumor and hematological cancer patients will be primarily driven by type and timing of treatment. This hypothesis is supported by our publications assessing early post-booster immune responses, however, the research proposed here will allow us to T cell and antibody memory at 1 year post booster. Furthermore, by tracking clonal T cell populations and epitope specific antibody responses within individual cancer patients, we hypothesize that can identify key parameters driving heterogeneity in SARS-CoV2 mRNA booster responses. We will address our hypotheses via in-depth immunological studies using samples collected prospectively through the COVID-19 Vaccine Study of Infections and Immune REspoNse (SIIREN) at The Ohio State University Comprehensive Cancer Center.