U01AI167789

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

Vanderbilt University Medical Center

NOT APPLICABLE

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Nashville, Tennessee 37203 United States

Single Zip Code

NIAID Clinical Trial Implementation Cooperative Agreement (U01 Clinical Trial Required) (PAR-21-083)

Amendment Since initial award the total obligations have increased 359% from $913,378 to $4,188,390.