Immune response to COVID-19 vaccination in individuals with immune disorders

患有免疫疾病的个体对 COVID-19 疫苗接种的免疫反应

• 批准号: 10927974
• 负责人: Emily Ricotta
• 金额: $ 120.58万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10927974
• 关键词: 2019-nCoV; ACE2; Anaphylaxis; Antibodies; Attenuated Vaccines; Authorization documentation; B-Cell Antigen Receptor; B-Lymphocytes; Binding; COVID-19; COVID-19 vaccination; COVID-19 vaccine; Chickenpox Vaccine; Chronic Granulomatous Disease; Common Variable Immunodeficiency; Complement; Cytokinesis; DNA; Data; Defect; Disease; Dose; Dryness; Emergency Situation; Enrollment; Epstein-Barr Virus Infections; Exclusion; Functional disorder; Funding; General Population; Genes; Genetic Recombination; Haemophilus influenzae type b; Herd Immunity; Hereditary Disease; Immune; Immune System Diseases; Immune response; Immunity; Immunoglobulin G; Immunologic Deficiency Syndromes; Immunologics; Impairment; Individual; Inflammasome; Inflammatory; Influenza; Interferon Type II; Interleukin-12; Job' s Syndrome; Laboratories; Leukocyte Adhesion Deficiency; Life; Light; Link; Literature; Magnesium; Measles-Mumps-Rubella Vaccine; Measures; Medicine; Minority Groups; National Institute of Allergy and Infectious Disease; Neonatal Onset Multisystem Inflammatory Disease; Neoplasms; Participant; Pathway interactions; Peripheral Blood Mononuclear Cell; Persons; Phosphatidylinositols; Phosphotransferases; Plasma; Polyglandular Autoimmune Syndrome Type I; Population; Prevalence; RNA; RNA vaccine; Reporting; SARS-CoV-2 BA.1; SARS-CoV-2 infection; STAT1 gene; Safety; Sampling; Serum; Severe Combined Immunodeficiency; Severities; Severity of illness; Stat3 protein; Symptoms; T cell response; T-Lymphocyte; United States; Update; Vaccination; Vaccines; Variant; Whole Blood; Wiskott-Aldrich Syndrome; X-Linked Agammaglobulinemia; authority; chronic infection; cohort; experience; healthy volunteer; immune activation; immunogenicity; immunomodulatory therapies; interest; neutrophil; novel; participant enrollment; post SARS-CoV-2 infection; response; saliva sample; sample collection; seroconversion; vaccine immunogenicity; vaccine trial

COVID-19 is caused by the novel SARS-CoV-2 and is associated with a hyper-inflammatory immune response which leads to severe and potentially life-threatening symptoms. Little is known about how and the extent to which COVID-19 presents in people with immunodeficiencies, but because of the known severity of the illness in the general population, vaccination against SARS-CoV-2 is critical. Understanding whether immunodeficient individuals produce an adequate immune response to the COVID-19 vaccine, as well as the number and type of AEs experienced in these people is necessary. Since the initiation of the study in April 2021, 308 study participants have been enrolled: 235 people with immune disorders, 73 healthy volunteers. Participant enrollment ended in January 2023 and sample collection ended July 2023 due to the ending of the COVID-19 emergency declaration and subsequent re-obligation of COVID-19 funds. We have collected samples from 1166 timepoints ranging from baseline through post-vaccination 5. Samples include microsamplers (dried whole blood), serum, plasma, PBMCs, and DNA extracted from buffy coat, although not all samples are available for every timepoint. We also collected 3173 saliva samples, RNA is available on 67 of 84 positives that were identified in the Department of Laboratory Medicine (11 pending RNA extraction). Analysis for the study is ongoing. From the first-round analytic cohort of 195 immune deficient people (IDP) and 35 healthy volunteers, anti-spike IgG was detected in 88% of IDP post-dose 2, increasing to 93% by six months post-dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed 1/3 that of healthy volunteers. IgG binding to Omicron BA.1 was lower than all other variants. Angiotensin-converting enzyme 2 pseudo-neutralization (% inhibition) was only modestly correlated with anti-spike IgG concentration. IgG levels were not significantly altered by participants use of different mRNA-based vaccines, immunomodulating treatments, and prior SARS-CoV-2 infections. While our data show that three doses of COVID-19 vaccinations induce anti-spike IgG in most IDP, additional doses are needed to achieve the levels of protection in healthy volunteers. Due to the strikingly reduced IgG response to Omicron BA.1, the efficacy of additional vaccinations, including bivalent vaccines, should be studied in this population. Continued analysis will focus on T and B cell receptor repertoire of the post-vaccine samples, as well as a detailed analysis of breakthrough COVID-19 infections, including individuals with repeat and persistent infection. We will also be doing a second-round update to report on IgG response through the remainder of the sampling timepoints.

COVID-19是由新型SARS-COV-2引起的，与过度炎性免疫反应有关，从而导致严重且潜在的威胁生命的症状。关于COVID-19在免疫缺陷患者中的如何和程度知之甚少，但是由于普通人群中疾病的已知严重程度，针对SARS-COV-2的疫苗接种至关重要。了解免疫缺陷的个体是否对COVID-19疫苗产生足够的免疫反应，以及在这些人中经历的AES数量和类型。 自2021年4月开始研究以来，已经招募了308名研究参与者：235人免疫疾病，73名健康志愿者。参与者的入学人数于2023年1月结束，样本收集于2023年7月结束，这是由于COVID-19紧急声明结束并随后重新封闭了Covid-19-19-19。 我们已经从基线到疫苗接种后的1166个时间点收集了样品。样品包括微型摄影器（干血），血清，血浆，PBMC和从Buffy Coat提取的DNA，尽管并非所有样品都可以在每个时间点上都可使用。我们还收集了3173个唾液样品，在实验室医学系中发现的84个阳性中有67个可以使用RNA（11次提取RNA提取）。 该研究的分析正在进行中。 From the first-round analytic cohort of 195 immune deficient people (IDP) and 35 healthy volunteers, anti-spike IgG was detected in 88% of IDP post-dose 2, increasing to 93% by six months post-dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed 1/3 that of healthy volunteers. IgG与Omicron BA.1的结合低于所有其他变体。血管紧张素转换酶2伪中和（％抑制）仅与抗尖峰IgG浓度相关。参与者使用不同的基于mRNA的疫苗，免疫调节治疗和先前的SARS-COV-2感染不会显着改变IgG水平。尽管我们的数据表明，三剂COVID-19疫苗接种在大多数IDP中诱导抗Spike IgG，但需要额外的剂量来实现健康志愿者的保护水平。由于IgG对Omicron BA.1的反应大幅降低，应在该人群中研究其他疫苗接种（包括二价疫苗）的疗效。 持续分析将集中于疫苗后样本的T和B细胞受体库，以及对Covid-19感染的详细分析，包括重复和持续感染的人。我们还将通过其余的采样时间点进行第二轮更新，以报告IgG响应。