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

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

Abstract

Background: Live 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.

Methods: We 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.

Results: A 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.

Conclusion: No 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.

Keywords: MMR; RMRP; clinical trial; combined immunodeficiency; immunization; vaccination; varicella zoster virus.

Copyright © 2020 Vakkilainen, Kleino, Honkanen, Salo, Kainulainen, Gräsbeck, Kekäläinen, Mäkitie and Klemetti.

Figures

FIGURE 1
FIGURE 1
Recruitment to the clinical trial of safety and efficacy of live varicella zoster virus vaccine in patients with cartilage-hair hypoplasia.
FIGURE 2
FIGURE 2
Varicella zoster virus antigen response in CHH patient samples. Peripheral blood mononuclear cells of naïve and post-vaccine paired patient samples showed statistically significant induction of cellular immunity in interferon-γ elispot antigen assay. The level of induction (mean, black lines) was similar to a single healthy control.

References

    1. Ridanpaa M, Van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, et al. Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell. (2001) 104:195–203. 10.1016/S0092-8674(01)00205-7
    1. Thiel CT, Horn D, Zabel B, Ekici AB, Salinas K, Gebhart E, et al. Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am J Hum Genet. (2005) 77:795–806. 10.1086/497708
    1. Kostjukovits S, Degerman S, Pekkinen M, Klemetti P, Landfors M, Roos G, et al. Decreased telomere length in children with cartilage-hair hypoplasia. J Med Genet. (2017) 54:365–70. 10.1136/jmedgenet-2016-104279
    1. Rogler LE, Kosmyna B, Moskowitz D, Bebawee R, Rahimzadeh J, Kutchko K, et al. Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia. Hum Mol Genet. (2014) 23:368–82. 10.1093/hmg/ddt427
    1. Kostjukovits S, Klemetti P, Valta H, Martelius T, Notarangelo LD, Seppanen M, et al. Analysis of clinical and immunologic phenotype in a large cohort of children and adults with cartilage-hair hypoplasia. J Allergy Clin Immunol. (2017) 140:612-4.e5. 10.1016/j.jaci.2017.02.016
    1. Ip W, Gaspar HB, Kleta R, Chanudet E, Bacchelli C, Pitts A, et al. Variable phenotype of severe immunodeficiencies associated with RMRP gene mutations. J Clin Immunol. (2015) 35:147–57. 10.1007/s10875-015-0135-7
    1. McKusick VA, Eldridge R, Hostetler JA, Ruangwit U, Egeland JA. Dwarfism in the amish. Ii. Cartilage-hair hypoplasia. Bullet Johns Hopk Hosp. (1965) 116:285–326.
    1. Lux SE, Johnston RB, Jr., August CS, Say B, Penchaszadeh VB, Rosen FS, et al. Chronic neutropenia and abnormal cellular immunity in cartilage-hair hypoplasia. New Engl J Med. (1970) 282:231–6. 10.1056/NEJM197001292820501
    1. Eisner JM, Russell M. Cartilage hair hypoplasia and multiple basal cell carcinomas. J Am Acad Dermatol. (2006) 54(Suppl. 2):S8–10. 10.1016/j.jaad.2005.03.055
    1. Bacchetta J, Ranchin B, Brunet AS, Bouvier R, Duquesne A, Edery P, et al. Autoimmune hypoparathyroidism in a 12-year-old girl with McKusick cartilage hair hypoplasia. Pediatr Nephrol (Berlin Germany). (2009) 24:2449–53. 10.1007/s00467-009-1256-0
    1. Horn J, Schlesier M, Warnatz K, Prasse A, Superti-Furga A, Peter HH, et al. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia. Hum Immunol. (2010) 71:916–9. 10.1016/j.humimm.2010.06.002
    1. Vatanavicharn N, Visitsunthorn N, Pho-iam T, Jirapongsananuruk O, Pacharn P, Chokephaibulkit K, et al. An infant with cartilage-hair hypoplasia due to a novel homozygous mutation in the promoter region of the RMRP gene associated with chondrodysplasia and severe immunodeficiency. J Appl Genet. (2010) 51:523–8. 10.1007/BF03208884
    1. Makitie O, Kaitila I. Cartilage-hair hypoplasia–clinical manifestations in 108 Finnish patients. Eur J Pediatr. (1993) 152:211–7. 10.1007/BF01956147
    1. Rider NL, Morton DH, Puffenberger E, Hendrickson CL, Robinson DL, Strauss KA. Immunologic and clinical features of 25 Amish patients with RMRP 70 A–>G cartilage hair hypoplasia. Clin Immunol (Orlando Fla). (2009) 131:119–28. 10.1016/j.clim.2008.11.001
    1. Pierce GF, Polmar SH. Lymphocyte dysfunction in cartilage-hair hypoplasia: evidence for an intrinsic defect in cellular proliferation. J Immunol. (1982) 129:570–5.
    1. Saulsbury FT, Winkelstein JA, Davis LE, Hsu SH, D’Souza BJ, Gutcher GR, et al. Combined immunodeficiency and vaccine-related poliomyelitis in a child with cartilage-hair hypoplasia. J Pediatr. (1975) 86:868–72. 10.1016/S0022-3476(75)80216-2
    1. Otani N, Baba K, Okuno T. Interferon-gamma release assay: a simple method for detection of varicella-zoster virus-specific cell-mediated immunity. J Immunol Methods. (2009) 351:71–4. 10.1016/j.jim.2009.09.010
    1. Smith JG, Liu X, Kaufhold RM, Clair J, Caulfield MJ. Development and validation of a gamma interferon ELISPOT assay for quantitation of cellular immune responses to varicella-zoster virus. Clin Diagn Labor Immunol. (2001) 8:871–9. 10.1128/CDLI.8.5.871-879.2001
    1. Sobh A, Bonilla FA. Vaccination in primary immunodeficiency disorders. J Allergy Clin Immunol Pract. (2016) 4:1066–75. 10.1016/j.jaip.2016.09.012
    1. Vakkilainen S, Makitie R, Klemetti P, Valta H, Taskinen M, Husebye ES, et al. A wide spectrum of autoimmune manifestations and other symptoms suggesting immune dysregulation in patients with cartilage-hair hypoplasia. Front Immunol. (2018) 9:2468. 10.3389/fimmu.2018.02468
    1. Vakkilainen S, Taskinen M, Klemetti P, Pukkala E, Mäkitie O. A 30-year prospective follow-up study reveals risk factors for early death in cartilage-hair hypoplasia. Front Immunol. (2019) 10:1581. 10.3389/fimmu.2019.01581
    1. Kreth HW, Lee BW, Kosuwon P, Salazar J, Gloriani-Barzaga N, Bock HL, et al. Sixteen years of global experience with the first refrigerator-stable varicella vaccine (Varilrix). BioDrugs. (2008) 22:387–402. 10.2165/0063030-200822060-00005
    1. Fedeli U, Zanetti C, Saia B. Susceptibility of healthcare workers to measles, mumps rubella and varicella. J Hosp Infect. (2002) 51:133–5. 10.1053/jhin.2002.1222
    1. Kennedy RB, Ovsyannikova IG, Thomas A, Larrabee BR, Rubin S, Poland GA. Differential durability of immune responses to measles and mumps following MMR vaccination. Vaccine. (2019) 37:1775–84. 10.1016/j.vaccine.2019.02.030
    1. Michalik DE, Steinberg SP, LaRussa PS, Edwards KM, Wright PF, Arvin AM, et al. Primary vaccine failure after 1 Dose of varicella vaccine in healthy children. J Infect Dis. (2008) 197:944–9. 10.1086/529043
    1. Slifka MK, Amanna IJ. Role of multivalency and antigenic threshold in generating protective antibody responses. Front Immunol. (2019) 10:956. 10.3389/fimmu.2019.00956
    1. Buchbinder D, Hauck F, Albert MH, Rack A, Bakhtiar S, Shcherbina A, et al. Rubella virus-associated cutaneous granulomatous disease: a unique complication in immune-deficient patients, not limited to DNA repair disorders. J Clin Immunol. (2019) 39:81–9. 10.1007/s10875-018-0581-0
    1. Harrington WE, Mató S, Burroughs L, Carpenter PA, Gershon A, Schmid DS, et al. Vaccine oka varicella meningitis in two adolescents. Pediatrics. (2019) 144:e20191522. 10.1542/peds.2019-1522

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