Mycophenolate and lower graft function reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination

Abstract

In late 2009 transplant organizations recommended that kidney recipients be vaccinated for pandemic H1N1 influenza (pH1N1); however, the vaccine efficacy was unknown. We had offered a monovalent non-adjuvanted pH1N1 vaccine to transplant recipients. Here we compared the pre- and post-vaccination seroresponses of 151 transplant recipients to that of 71 hemodialysis patients and 30 healthy controls. Baseline seroprotection was similar between groups but was significantly different at 1 month (44, 56, and 87%, respectively). Seroconversion was significantly less common for transplant recipients (32%) than dialysis patients (45%) and healthy controls (77%). After adjusting for age and gender, dialysis patients were significantly more likely (2.7-fold) to achieve new seroprotection than transplant recipients. The likelihood of seroprotection in transplant recipients was significantly reduced by mycophenolate use (adjusted odds ratio 0.24), in a dose-dependent manner, and by reduced eGFR (adjusted odds ratio 0.16 for worst to best). Seroprotection and geometric mean antibody titers increased substantially in 49 transplant recipients who subsequently received the 2010 seasonal influenza vaccine. Thus, patients requiring renal replacement therapy had reduced seroresponses to vaccination with the monovalent vaccine compared with healthy controls. Transplant recipient responses were further reduced if they were receiving mycophenolate or had significantly lower graft function.

A simple score can identify kidney transplant recipients at high risk of severe infection over the following 2 years

“…30 Reduced eGFR in kidney transplant recipients has also been associated with poor vaccine responsiveness. 31 These factors may in part explain why reduced eGFR was an important risk factor for severe infection in our study. 16 Mycophenolate use had previously been shown to be associated with increased risk of infection.…”

“…For example, defective phagocytosis can be caused by uremic toxins, iron overload, and anemia of renal disease . Reduced eGFR in kidney transplant recipients has also been associated with poor vaccine responsiveness . These factors may in part explain why reduced eGFR was an important risk factor for severe infection in our study …”

Immunizations following solid-organ transplantation

“…Although patients had a significant increase in antibody levels initially, titers significantly declined by 3 months after liver transplant. Studies with influenza vaccine have also shown that humoral responses are greater in hemodialysis patients compared with transplant recipients [2,3].…”

“…vaccine in the first year were immunized in the first 6 months after transplant. The use of mycophenolate mofetil (MMF) is also a well known factor leading to diminished immunogenicity [3,18]. A recent study found that higher doses of MMF of at least 2 g daily reduced the seroconversion rate of influenza vaccine [16 && ].…”

Seasonal influenza vaccination of high-risk adults

“…Influenza vaccination protected against influenza-like illness (50-70%) and against laboratory-confirmed influenza (70%) [120][121][122].…”