SARS-CoV-2 correlates of protection in a Latino-origin population

SARS-CoV-2在全球的迅速传播对癌症人群产生了重大影响。造血干细胞移植（HSCT）受者感染SARSCoV-2导致预后不良，存活率约为68%。免疫介导的保护是保护移植人群的关键。然而，我们对HSCT患者群体中疫苗诱导的免疫反应的理解存在重大差距。这项拟议的研究将极大地促进我们对以下方面的理解：1)免疫受损人群中mRNA疫苗驱动的免疫反应；2)hst人群中SARS-CoV-2抗原特异性T细胞和B细胞反应的功能；3)适应性免疫反应在控制突破性感染中的作用。这项建议的结果将产生短期和长期的影响。在短期内，我们将确定一系列关键参数，这些参数可以改善大流行期间造血干细胞移植患者的生活质量。这些研究将确定mRNA SARS-CoV-2疫苗增强前后的免疫原性。在两个队列中，我们将监测无症状和有症状的SARS-CoV-2感染，并评估接近突破性感染时的疫苗免疫水平。从长期来看，SARS-CoV-2大流行是过去20年来新型冠状病毒的第三次全球传播。未来可能会爆发目前未知的冠状病毒，因此，现在就确定高风险人群对疫苗接种的反应，以及他们是否需要频繁加强疫苗接种或可能需要更高的疫苗剂量，这一点至关重要。鉴于mRNA疫苗平台的速度和有效性，该疫苗平台的使用极有可能扩大到对抗其他已知病原体，但也可用于对抗任何范围的潜在新出现的病毒病原体。现在需要确定纵向队列中不同风险群体对mRNA疫苗反应的强度、广度和持久性，以便为未来的流行病/大流行做好准备。

The rapid global spread of SARS-CoV-2 has had a significant impact on the cancer population. SARSCoV-2 infection of hematopoietic stem cell transplant (HSCT) recipients leads to a poor prognosis with a ~68% survival rate. Immune mediated protection is critical to protect the HSCT population. However, there are significant gaps in our understanding of vaccine induced immune responses in the HSCT patient population. This proposed research will greatly advance our understanding of 1) mRNA vaccine driven immune responses in immune compromised subject populations, and 2) the functionality of the SARS-CoV-2 antigen specific T and B cell response in the HSCT population; 3) the role of the adaptive immune response in controlling breakthrough infections. The results of this proposal will have both short and long-term impacts. In the short term we will define a series of critical parameters that could improve the quality of life of HSCT patients during the pandemic. These studies will define the immunogenicity of mRNA SARS-CoV-2 vaccines before and after boosters. In two cohorts we will surveil for asymptomatic and symptomatic SARS-CoV-2 infections and evaluate the level of vaccine immunity close to the time of the breakthrough infection. In the long-term the SARS-CoV-2 pandemic was the 3rd global transmission of a novel coronavirus in the past 20 years. It is likely that there will be outbreaks in the future with currently unknown coronaviruses, and thus it is critical to determine now how high-risk groups respond to vaccination and if they require frequent booster vaccinations or potentially higher vaccine doses. Given the speed and efficacy of the mRNA vaccine platform, it is highly likely that the use of this vaccine platform will be expanded to combat other known pathogens, but also could be used to combat any range of potential emerging viral pathogens. The strength, breadth, and durability of responses to mRNA vaccines needs to be determined in different risk groups in longitudinal cohorts now, in order to prepare for future epidemics/pandemics.