Study: Live vaccines safe, effective in pediatric transplant recipients
Key takeaways:
- Most transplant recipients developed and maintained protective antibodies up to 1 year after varicella or MMR vaccination.
- Five children developed varicella rash; none developed measles or graft rejection.
Most pediatric transplant recipients who received live-attenuated viral vaccines after transplant developed protective antibodies that persisted for up to a year after vaccination with no significant safety events, researchers found.
Based on the findings, which were published in JAMA Pediatrics, the researchers recommend providers consider vaccinating patients who are not immune to measles, mumps, rubella or varicella.
“In today’s world, measles, mumps and varicella are circulating in the community, and nonimmune transplant recipients are at risk for community acquisition of these potentially fatal infections,” Amy G. Feldman, MD, PhD, FAASLD, associate professor of pediatrics at the University of Colorado School of Medicine, medical director of the pediatric liver transplant center at Children’s Hospital Colorado and president-elect of the Society of Pediatric Liver Transplantation, told Healio.
Feldman told Healio in 2019 that just half of children who had received liver transplants were up to date on childhood vaccines compared with 70% of healthy children. Additionally, research has shown that 16% of transplant recipients are hospitalized with vaccine-preventable diseases within 5 years after their transplant.
In their latest study, Feldman and colleagues examined the outcomes of 383 pediatric transplant recipients (median age, 8.2 years; interquartile range, 4.6-13.6) from 20 pediatric transplant centers who received doses of MMR or varicella zoster virus vaccines between Jan. 1, 2002, and May 31, 2023. They measured patients’ antibody levels at 1 to 3 months after administration and again after 1 year. They also kept track of any adverse events that occurred after in the month vaccination.
Most participants (372) received a liver transplant; nine received a kidney transplant, and two received liver and kidney transplants, according to the authors. Participants received at least one dose of a live-attenuated viral vaccine a median of 6.2 years (interquartile range, 3.1-11.2 years) after their transplant.
At the time of vaccination, 66.7% of patients were on low-level immunosuppression, 18.8% were on medium level immunosuppression and 14.6% were on high-level immunosuppression.
Out of 186 children who received the VZV vaccine, 71% had protective antibodies after 1 to 3 months of follow-up. After 1 year, 53 out of 68 children (77.9%) had protective levels of antibodies. The researchers reported that five children developed a varicella rash within a month after they were vaccinated.
At 1 to 3 months after MMR vaccination, 84%, 82.9% and 97.3% of 207 children had protective antibodies for measles, mumps and rubella, respectively. After 1 year, 91.8% and 95.9% of 73 children had protective levels of antibodies for measles and rubella; 72.4% of 58 children had protective antibodies for mumps. The authors noted medium or low immunosuppression levels were associated with a greater likelihood for developing protective measles antibodies.
No children developed measles, mumps, rubella or varicella during the 1-year study period, according to Feldman and colleagues. Additionally, no children experienced graft rejection after vaccination.
Based on the results, Feldman said recommendations for liver transplant care should suggest checking MMR and VZV antibody levels after transplant. Further, she said providers should consider vaccinating children who are not immune.
“This article is very timely with the recent measles outbreaks across the United States,” Feldman said. “With measles circulating, it is critically important for physicians taking care of transplant recipients to consider if the theoretical risk of vaccine-acquired measles outweighs the very real risk of community acquisition of measles.”
According to Feldman, the researchers plan to continue studying live-attenuated viral vaccines in the pediatric kidney and heart community, as well as barriers that are preventing pediatric transplant recipients from receiving live vaccines.
“We want to learn more about parental hesitancies, provider hesitancies and system-level barriers that may prevent new recommendations from being disseminated and implemented,” she said.
Perspective
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Historically, given concerns regarding risks associated with live-attenuated viral vaccination in the setting of chronic immunosuppression, pediatric solid organ transplant (SOT) recipients have not received MMR or VZV after transplant. However, given episodic clusters of varicella and mumps infection as well as measles outbreaks, ensuring optimal protection from these contagious viral infections in pediatric SOT recipients is increasingly critical.
Prior studies in adult and pediatric SOT recipients have indicated that live-attenuated viral vaccination with MMR and/or VZV in these patients is likely safe when limited to targeted SOT recipients who are beyond a year after transplant and on low-level immunosuppression. However, before this study group’s work, there have been no large-scale multicenter evaluations of MMR and VZV immunization in pediatric SOT recipients.
This is the largest cohort of pediatric SOT recipients having received live- attenuated MMR or VZV infection. The study includes 383 children from 20 transplant centers across the U.S. The majority of children included in the study had undergone liver transplant, and there were a small number of kidney or liver-kidney recipients. The study investigators quantified immunosuppression level as low, medium or high and performed an analysis to assess for statistical association between immunosuppression level and vaccine-induced antibody responses.
Post-vaccine antibody levels for MMR and VZV were obtained at 1 to 3 months after immunization and at 1 year after immunization. Notably, protective antibody responses were seen at the 1- to 3-month time point in 71% (VZV), 84% (measles), 82.9% (mumps) and 97.3% (rubella) of live virus vaccine recipients who were previously seronegative. In the subset of patients who were seropositive at the 1- to 3-month timepoint and for whom antibody testing was obtained at 1 year following vaccination, the majority continued to have protective antibodies. A small number (n = 5) of VZV vaccine recipients developed rash in the month after VZV immunization.
Thus, live virus vaccination of pediatric SOT recipients with MMR and/or VZV is successful at inducing protective antibody response to the viruses contained in these vaccines. These findings support and extend those from a prior publication from this study group (linked below).
Key takeaways:
Immunization of pediatric SOT recipients with VZV and/or MMR is safe and results in protective antibody responses.
Center-specific protocols for live virus vaccine eligibility were used in this study. Therefore, each transplant center considering MMR or VZV administration to pediatric SOT recipients should develop its own eligibility criteria based on duration of time after transplant and degree of immunosuppression.
Future research is needed to better understand which clinical and immunologic factors are associated with sustained post-vaccine immunity following VZV and MMR immunization in pediatric SOT recipients. Similarly, understanding which patients are more likely to have lack of antibody response to these vaccines when administered post-transplant will help guide other possible preventive efforts and will guide future studies of post-transplant live virus vaccination.
Reference:
Feldman AG, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.37602.
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