BCG Moreau Vaccine Safety Profile and NK Cells\u2014Double Protection Against Disseminated BCG Infection in Retrospective Study of BCG Vaccination in 52 Polish Children with Severe Combined Immunodeficiency

Ewa Bernatowska,Nel Dąbrowska-Leonik,Bożena Mikołuć,Maria Krasińska,Małgorzta Skomska-Pawliszak,Beata Wolska-Kuśnierz,Anna Lutyńska,Barbara Piątosa,Małgorzata Pac,Maria Korzeniewska-Koseła,Anna Wieteska-Klimczak,Capucine Pïcard ,Jean‐Laurent Casanova ,Edyta Heropolitańska-Pliszka ,Katarzyna Bernat-Sitarz,Janusz Ksia̧żyk ,Jacques J.m Van Dongen ,Katarzyna Krzysztopa-Grzybowska,Mirjam Van Den Burg,Ewa Augustynowicz,Teresa Jackowska,Nadia Bohynikova,Barbara Pietrucha,Ewa Augustynowicz‐Kopeć

doi:10.1007/s10875-019-00709-1

Abstract

ObjectivesThe aim of the study was to estimate the rate of adverse reactions to live BCG Moreau vaccine, manufactured by Biomed in Poland, in severe combined immunodeficiency (SCID) patients.MaterialThe profiles of 52 SCID patients vaccinated at birth with BCG, hospitalized in Children’s Memorial Health Institute, Warsaw (CMHI), in the years 1980–2015 were compared with those of 349 BCG-vaccinated SCID patients from other countries analyzed by Beatriz E. Marciano et al. in a retrospective study (Marciano et al. J Allergy Clin Immunol. 2014;133(4):1134–1141).ResultsSignificantly less disseminated BCG infections (10 out of 52 SCID, 19%) occurred in comparison with Marciano study—119 out of 349, 34% (p = 0.0028), with no death in patients treated with SCID anti-TB drug, except one in lethal condition. In our study, disseminated BCG infection was observed only in SCID with T-B+NK- phenotype and significantly lower NK cell counts (p = 0.0161). NK cells do not influence on the frequency of local BCG reaction. A significantly higher number of hematopoietic stem cells transplantations (HSCT) were performed in CMHI study (p = 0.0001). Anti-TB treatment with at least two medicines was provided.ConclusionThe BCG Moreau vaccine produced in Poland, with well-documented genetic characteristics, seems to be safer than other BCG substrains used in other regions of the world. Importantly, NK cells seem to play a role in protecting SCID patients against disseminated BCG complications, which NK- SCID patients are more prone to. HSCT and TB therapy could be relevant due to the patients’ survival and the fact that they protect against BCG infection.

Highlights

BCG vaccination administered at birth or shortly after birth is included in vaccination schedules in countries with a high prevalence of tuberculosis (TB)
Disseminated BCG infection occurred in 10 severe combined immunodeficiency (SCID) patients out of 52 vaccinated with BCG, twelve localized complications were present in both group, separately or together with disseminated BCG infection. (Table S1)
Disseminated BCG infection was diagnosed in 10 SCID patients with TB+NKphenotype, in 6 with IL2RG mutation, in one patient with JAK3 deficiency and in 3 with unknown mutations

Summary

Introduction

BCG vaccination administered at birth or shortly after birth is included in vaccination schedules in countries with a high prevalence of tuberculosis (TB). Three different BCG vaccine substrains, Danish 1331, Tokyo 172–1, and Russian BCG-I, are recommended by the World Health Organization (WHO) as International Reference Reagents (IRR). These three substrains constitute the major proportion of BCG vaccine production worldwide as they are supplied by. The majority of locally produced BCG vaccine substrains have not been well-characterized. No BCG substrain was found markedly superior to other strains and there is no global consensus on the choice of an optimal BCG substrain for general use [3,4,5]

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