Comparison of High Dose vs. Standard Dose Influenza Vaccines in Lung Allograft Recipients

同种异体肺移植受者中高剂量与标准剂量流感疫苗的比较

• 批准号: 10576411
• 负责人: NATASHA Bassam HALASA
• 金额: $ 83.85万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-18 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576411
• 关键词: 16 year old; Academic Medical Centers; Ache; Acute; Address; Adult; Adverse event; Alabama; Allografting; Antibodies; Antibody titer measurement; Antigens; B-Lymphocyte Subsets; B-Lymphocytes; Biopsy; CD4 Positive T Lymphocytes; Cellular Assay; Chronic; Clinical; Cytometry; Development; Disease; Dose; Double-Blind Method; Enrollment; Environmental Exposure; Evaluation; Fatigue; Fever; Frequencies; Functional disorder; HLA Antigens; Headache; Hemagglutination; Immune response; Immunologics; Immunophenotyping; Immunosuppression; Individual; Induration; Influenza; Influenza A virus; Influenza B Virus; Influenza vaccination; Injections; Knowledge; Lung Transplantation; Malaise; Measurement; Measures; Morbidity - disease rate; Myalgia; Nausea; Organ Transplantation; Pain; Patients; Phase; Phenotype; Population; Prevention strategy; Publishing; Randomized; Reaction; Recommendation; Redness; Regimen; Reporting; Respiratory Failure; Risk; Safety; Seasons; Serious Adverse Event; Severities; Site; Solid; Swelling; T-Cell Activation; T-Lymphocyte; Testing; Transplant Recipients; Universities; Vaccination; Vaccine Antigen; Vaccines; Vomiting; Washington; comorbidity; exhaustion; high risk; immunogenic; immunogenicity; immunosuppressed; improved; influenza virus vaccine; influenzavirus; lung allograft; organ transplant recipient; pathogen; phase II trial; post-transplant; preservation; response; seasonal influenza; senescence; seroconversion; side effect; transplant centers; trial comparing; vaccination strategy; vaccine immunogenicity; vaccine strategy; vaccine trial

PROJECT SUMMARY Influenza virus is a significant pathogen in solid organ transplant (SOT) recipients, including lung allograft recipients. Moreover, compared to other SOT, lung allograft recipients have more severe influenza disease. However, due to requisite immunosuppression, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. The first study, conducted in adult SOT recipients, reported that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. The second study, another phase II trial in adult SOT recipients with a median post-transplant period of 18 months, reported that two doses of SD-IIV administered one month apart was more immunogenic than one-dose of SD-IIV. While promising, these studies lack evaluation in the early post-transplant period, when SOT patients are most vulnerable to influenza. Moreover, these studies had limited inclusion of lung transplant recipients, a population that is most at risk for influenza-related comorbidities, including respiratory failure, acute cellular rejection, and chronic lung allograft dysfunction. Finally, the administration of two doses of HD-IIV in the same influenza season has not previously been evaluated in SOT recipients. Thus, the optimal immunization strategy for lung allograft recipients in the early post-transplant period remains unknown. In addition, the immunologic predictors and correlates of influenza vaccine immunogenicity in lung allograft recipients have not been well-defined. The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMTs) to influenza antigens compared to those receiving two doses of SD-QIV. To test this hypothesis and address the critical knowledge gaps outlined above, we propose to conduct a phase II, multi-center, randomized-controlled immunogenicity and safety trial comparing two doses HD-QIV to two doses SD-QIV administered one month apart in lung allograft recipients who are ≥16 years and 1-35 months post-transplant. This study will be conducted at five lung transplant centers—Vanderbilt University Medical Center, Duke University, Northwestern University, University of Alabama in Birmingham, and University of Washington. The results of this study will illuminate immune responses in adult lung allograft recipients and help guide vaccine recommendations during the early post-transplant period. Moreover, our findings may help guide optimal vaccine strategies in other immunosuppressed populations.

项目总结