The Safety and Efficacy of Live Viral Vaccines in Patients With Cartilage-Hair Hypoplasia.

Svetlana Vakkilainen,Leena Kainulainen,Michaela Gräsbeck,Jarno Honkanen,Harri Salo,Paula Klemetti,Iivari Kleino,Outi Mäkitie,Eliisa Kekäläinen

doi:10.3389/fimmu.2020.02020

Abstract

BackgroundLive viral vaccines are generally contraindicated in patients with combined immunodeficiency including cartilage-hair hypoplasia (CHH); however, they may be tolerated in milder syndromes. We evaluated the safety and efficacy of live viral vaccines in patients with CHH.MethodsWe analyzed hospital and immunization records of 104 patients with CHH and measured serum antibodies to measles, mumps, rubella, and varicella zoster virus (VZV) in all patients who agreed to blood sampling (n = 50). We conducted a clinical trial (ClinicalTrials.gov identifier: NCT02383797) of live VZV vaccine on five subjects with CHH who lacked varicella history, had no clinical symptoms of immunodeficiency, and were seronegative for VZV; humoral and cellular immunologic responses were assessed post-immunization.ResultsA large proportion of patients have been immunized with live viral vaccines, including measles-mumps-rubella (MMR) (n = 40, 38%) and VZV (n = 10, 10%) vaccines, with no serious adverse events. Of the 50 patients tested for antibodies, previous immunization has been documented with MMR (n = 22), rubella (n = 2) and measles (n = 1) vaccines. Patients with CHH demonstrated seropositivity rates of 96%/75%/91% to measles, mumps and rubella, respectively, measured at a medium of 24 years post-immunization. Clinical trial participants developed humoral and cellular responses to VZV vaccine. One trial participant developed post-immunization rash and knee swelling, both resolved without treatment.ConclusionNo serious adverse events have been recorded after immunization with live viral vaccines in Finnish patients with CHH. Patients generate humoral and cellular immune response to live viral vaccines. Immunization with live vaccines may be considered in selected CHH patients with no or clinically mild immunodeficiency.

Highlights

MATERIALS AND METHODSCartilage-hair hypoplasia (CHH, MIM #250250) is a rare skeletal dysplasia with combined immunodeficiency
The clinical characteristics of this cohort have been reported in our recent publication [20], According to our clinical immunodeficiency categorization [21] and based on data on childhood symptoms available in 103/104 patients, 62 patients were classified as clinically asymptomatic, another 28 individuals demonstrated symptoms of humoral immunodeficiency with recurrent respiratory tract infections and/or sepsis, and the remaining 13 patients were regarded as having combined immunodeficiency in childhood, based on the additional features of autoimmunity or opportunistic infections
Of the 50 patients tested for antibodies against measles (n = 50), mumps (n = 48), rubella (n = 48), and varicella (n = 50) viruses, previous immunization has been documented with MMR (n = 22), varicella zoster virus (VZV) (n = 9), rubella (n = 2) and measles (n = 1) vaccines

Summary

Introduction

Cartilage-hair hypoplasia (CHH, MIM #250250) is a rare skeletal dysplasia with combined immunodeficiency. Patients with CHH demonstrate highly variable degree of immune defect, ranging from asymptomatic lymphopenia to severe combined immunodeficiency necessitating hematopoietic stem cell transplantation [5, 6]. Several CHH patients with severe varicella, but not fatalities, have been reported [8,9,10,11,12]. In a more recent Amish series of 25 patients, neither antiviral medications nor hospitalizations were needed for varicella [14]. Live viral vaccines are generally contraindicated in patients with combined immunodeficiency including cartilage-hair hypoplasia (CHH); they may be tolerated in milder syndromes. We evaluated the safety and efficacy of live viral vaccines in patients with CHH

Methods

Results

Conclusion