Multimodal Safety Assessment of Measles-Mumps-Rubella Vaccination After Pediatric Liver Transplantation

Laure F. Pittet; Charlotte M. Verolet; Valérie A. McLin; Barbara E. Wildhaber; Maria Rodriguez; Pascal Cherpillod; Laurent Kaiser; Claire-Anne Siegrist; Klara M. Posfay-Barbe

Disclosures

American Journal of Transplantation. 2019;19(3):844-854. 

In This Article

Abstract and Introduction

Abstract

Live-attenuated vaccines are currently contraindicated in solid-organ transplant recipients. However, the risk of vaccine-preventable infections is lifelong, and can be particularly severe after transplantation. In this prospective interventional national cohort study, 44 pediatric liver transplant recipients with measles IgG antibodies <150 IU/L (below seroprotection threshold) received measles-mumps-rubella vaccine (MMR) at a median of 6.3 years posttransplantation (interquartile range, 4.0 to 10.9). A maximum of two additional doses were administered in nonresponders or when seroprotection was lost. Vaccine responses occurred in 98% (95% confidence interval [CI], 88-100) of patients. Seroprotection at 1-, 2-, and 3-year follow-up reached 62% (95% CI, 45-78), 86% (95% CI, 70-95), and 89% (95% CI, 67-99), respectively. All patients responded appropriately to the booster dose(s). Vaccinations were well tolerated and no serious adverse event attributable to vaccination was identified during the 8-week follow-up period (or later), using a multimodal approach including standardized telephone interviews, diarized side effect reporting, and monitoring of vaccinal virus shedding. We conclude that live attenuated MMR vaccine can be administered in liver transplant recipients fulfilling specific eligibility criteria (>1 year posttransplantation, low immunosuppression, lymphocyte count ≥0.75 G/L), inducing seroprotection in most subjects. (Clinicaltrials.gov number NCT01770119).

Introduction

Solid-organ transplantation (SOT) recipients are at high risk of severe infection due to their immunosuppressive therapy.[1] Measles is a particular threat for the immunocompromised host, with serious complications occurring in approximately 80%, of which 40% to 70% are fatal.[2,3] These patients often have atypical clinical manifestations and up to 30% do not present with the pathognomonic measles rash.[3] As no specific treatment exists, care is mostly supportive.[4]

A live attenuated vaccine is recommended for the prevention of measles worldwide. It is usually administered from the age of 9 to 12 months and is frequently distributed as a combined preparation against measles-mumps-rubella (MMR). Measles-containing vaccines are currently contraindicated after SOT due to the lack of safety data and the fear of instigating immune-mediated organ rejection or complications following uncontrolled viral replication.[5,6] Ideally, transplant candidates should be vaccinated before transplantation[5,7] using an accelerated schedule if needed (starting at the age of 6 months).[8] Nevertheless, in practice, pretransplant vaccination may not be performed because patients are either too young or considered too ill, or because of insufficient time before the planned SOT.[9] Indeed, we have previously reported that between 1990 and 2002 only 40% of patients older than 12 months were up-to-date for their MMR immunization at the pretransplantation visit.[10] Furthermore, in children vaccinated before SOT, antibodies may wane over time, in particular under the influence of immunosuppression.[7,11]

We previously reported excellent immunogenicity and tolerance for the live-attenuated varicella zoster vaccine in pediatric liver transplant (LT) recipients, to whom it is now offered as they meet specific eligibility criteria.[12] However, not all live viral vaccines are equally attenuated, and the replication pattern of measles containing vaccines exceeds that of the varicella zoster vaccine.[13] In addition, effective antivirals are not available in the event of disease resulting from measles immunization. Although measles-containing vaccines have been administered to LT recipients, it has been mainly limited to a few epidemic settings (mostly unpublished). So far, only five retrospective and prospective studies based in Japan and the United States have been performed (Table S1 in the Appendix S1), and no consensus yet exists on the safety of this practice.[14–19]

In the present study, we assessed the safety and immunogenicity of the MMR vaccine post-LT with a special emphasis on measles immunogenicity, given its consequences in immunosuppressed patients.

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