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Monogenic susceptibility to live viral vaccines.

ABSTRACT: Live attenuated viral vaccines (LAV) have saved millions of lives globally through their capacity to elicit strong, cross-reactive and enduring adaptive immune responses. However, LAV can also act as a Trojan horse to reveal inborn errors of immunity, thereby highlighting important protective elements of the healthy antiviral immune response. In the following article, we draw out these lessons by reviewing the spectrum of LAV-associated disease reported in a variety of inborn errors of immunity. We note the contrast between adaptive disorders, which predispose to both LAV and their wild type counterparts, and defects of innate immunity in which parenterally delivered LAV behave in a particularly threatening manner. Recognition of the underlying pathomechanisms can inform our approach to disease management and vaccination in a wider group of individuals, including those receiving immunomodulators that impact the relevant pathways.

SUBMITTER: Gothe F

PROVIDER: S-EPMC9586878 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Monogenic susceptibility to live viral vaccines.

Gothe Florian F Howarth Sophie S Duncan Christopher Ja CJ Hambleton Sophie S

Current opinion in immunology 20210606

Live attenuated viral vaccines (LAV) have saved millions of lives globally through their capacity to elicit strong, cross-reactive and enduring adaptive immune responses. However, LAV can also act as a Trojan horse to reveal inborn errors of immunity, thereby highlighting important protective elements of the healthy antiviral immune response. In the following article, we draw out these lessons by reviewing the spectrum of LAV-associated disease reported in a variety of inborn errors of immunity. ...[more]

PMID: 34107321

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Project description:ImportanceLive vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.ObjectiveTo determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.Design, setting, and participantsThis cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols.ExposuresExposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine.Main outcome and measureSafety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis.ResultsThe cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination.Conclusions and relevanceThe findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

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Monogenic susceptibility to live viral vaccines.

Publications

Monogenic susceptibility to live viral vaccines.

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