Therapy With m-TOR Inhibitors Decreases the Response to the Pandemic Influenza A H1N1 Vaccine in Solid Organ Transplant Recipients

Abstract

Concern has been raised regarding the response to vaccination in solid organ transplant recipients (SOTR) undergoing immunosuppressant regimens and the possibility of rejection related to the immune response associated with pandemic influenza H1N1-2009 vaccination. The goal of this study was to assess the immunogenicity, efficacy and safety of the pandemic vaccine in SOTR. We performed a multicenter prospective study in SOTR receiving the pandemic vaccine. Immunological response was determined in serum 5 weeks after vaccination by microneutralization assays, and immunoglobulins were measured by ELISA. Three hundred and forty-six SOTR were included. Preexisting seroprotection was detected in 13.6% of cases and rates of seroconversion and seroprotection after vaccination were 73.1% and 82.9%, respectively. Patients with baseline antibody titers had better geometric mean titers (GMT)-post after pandemic vaccination (339.4 vs. 121.4, p < 0.001). Younger age, liver disease and m-TOR inhibitor therapy were independently associated with lower seroprotection and GMT-post. There were no major adverse effects or rejection episodes.Pandemic vaccine was safe in SOTR and elicited an adequate response, although lower than in healthy individuals. This is the first study describing a decreased response after vaccination in patients receiving mTOR inhibitors who presented lower seroprotection rates and lower GMT-post.

Adjuvant Treatment With a Mammalian Target of Rapamycin Inhibitor, Sirolimus, and Steroids Improves Outcomes in Patients With Severe H1N1 Pneumonia and Acute Respiratory Failure*

“…This in turn interacts with activated NF-κB and activator protein 1 to prevent DNA binding and subsequent transcriptional activity, then terminating inflammation (15,16). A recent report showed decreased efficacy of H1N1 pandemic vaccination in organ transplant patients who received mTOR inhibitors (60). Our study, thus, showed improvement in oxygenation in the early phase of respiratory distress.…”

“…This means that the complementary effect of rapamycin and corticosteroids may modulate the over immune response in the early phase of severe H1N1 pneumonia. In addition, application of the H1N1 pandemic vaccine to organ transplant patients was shown to decrease efficacy of the vaccine in those who received mTOR inhibitors (60). Hence, inadequate immune responses can contribute to progressive disease as well (61,62).…”

Immunization after kidney transplantation—what is necessary and what is safe?

“…Mammalian target of rapamycin (mTOR) inhibitors might also inhibit the immune response to influenza vaccine in solid-organ transplant recipients. 27 Given the risk of rejection and subsequent need for high-dose immunosuppression, reducing immuno suppression to improve vaccination response is generally not recommended.…”

Humoral, T-cell and B-cell immune responses to seasonal influenza vaccine in solid organ transplant recipients receiving anti-T cell therapies

“…In particular, only few studies have assessed the influence of induction therapy on immune responses after organ transplantation [19,20]. We therefore studied humoral, T-cell, and B-cell responses after influenza vaccination in a prospective cohort of SOT recipients receiving basiliximab or ATG.…”