BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw

Ewa Bernatowska; Małgorzata Pac; Edyta Heropolitańska-Pliszka; Barbara Pietrucha; Nel Dąbrowska-Leonik; Małgorzata Skomska-Pawliszak; Katarzyna Bernat-Sitarz; Katarzyna Krzysztopa-Grzybowska; Beata Wolska-Kuśnierz; Nadia Bohynikova; Ewa Augustynowicz; Ewa Augustynowicz-Kopeć; Maria Korzeniewska-Koseła; Anna Wieteska-Klimczak; Janusz Książyk; Teresa Jackowska; Mirjam van den Burg; Jean-Laurent Casanova; Capucine Picard; Bożena Mikołuć

doi:10.3389/fped.2022.839111

BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw

Front Pediatr. 2022 May 19:10:839111. doi: 10.3389/fped.2022.839111. eCollection 2022.

Authors

Ewa Bernatowska¹, Małgorzata Pac¹, Edyta Heropolitańska-Pliszka¹, Barbara Pietrucha¹, Nel Dąbrowska-Leonik¹, Małgorzata Skomska-Pawliszak¹, Katarzyna Bernat-Sitarz¹, Katarzyna Krzysztopa-Grzybowska², Beata Wolska-Kuśnierz¹, Nadia Bohynikova¹, Ewa Augustynowicz³, Ewa Augustynowicz-Kopeć⁴, Maria Korzeniewska-Koseła⁵, Anna Wieteska-Klimczak⁶, Janusz Książyk⁶, Teresa Jackowska^{7

8}, Mirjam van den Burg⁹, Jean-Laurent Casanova^{10

11

12

13

14}, Capucine Picard^{15

16}, Bożena Mikołuć¹⁷

Affiliations

¹ Department of Immunology, Children's Memorial Health Institute, Warsaw, Poland.
² Department of Sera and Vaccines Evaluation, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
³ Department of Epidemiology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
⁴ Department of Microbiology, National Tuberculosis Reference Laboratory, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
⁵ Department of Tuberculosis Epidemiology and Surveillance, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
⁶ Department of Paediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland.
⁷ Department of Paediatrics, Medical Centre of Postgraduate Education, Warsaw, Poland.
⁸ Department of Paediatrics, Bielanski Hospital, Warsaw, Poland.
⁹ Department of Pediatrics, Laboratory for Pediatric Immunology, Leiden University Medical Center, Leiden, Netherlands.
¹⁰ Howard Hughes Medical Institute, New York, NY, United States.
¹¹ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University Hospital, New York, NY, United States.
¹² Necker Hospital for Sick Children, Paris Descartes University, Paris, France.
¹³ Laboratory of Human Genetics of Infectious Diseases, Imagine Institute, Necker Hospital for Sick Children, Paris, France.
¹⁴ Necker Hospital and School of Medicine, University Paris Descartes, Paris, France.
¹⁵ Imagine Institute, Université de paris, Paris, France.
¹⁶ Study Centre for Primary Immunodeficiency, Necker-Enfants, Malades Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.
¹⁷ Department of Paediatrics, Rheumatology, Immunology and Metabolic Bone Diseases, Medical University of Bialystok, Bialystok, Poland.

Abstract

Objective: We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated immunological defects, as well as the different BCG substrains.

Material: We studied adverse reactions to the locally-produced BCG Moreau vaccine, analyzed in patients with IEI diagnosed between 1980 and 2020 in the Department of Immunology, Children's Memorial Health Institute (CMHI), Warsaw. These results were compared with previously published studies.

Results: Significantly fewer disseminated BCG infections (BCGosis) were found in 11 of 72 (15%) SCID (Severe Combined Immunodeficiency) NK (Natural Killer)-phenotype patients, when compared with the 119 out of 349 (34%) (p = 0.0012) patients with SCID with BCG in other countries. Significantly fewer deaths caused by BCGosis were observed (p = 0.0402). A significantly higher number of hematopoietic stem cell transplantations (HSCTs) were performed in the CMHI study (p = 0.00001). BCGosis was found in six patients with Mendelian susceptibility to mycobacterial diseases (MSMD). Other patients with IEI prone to BCG complications, such as CGD (Chronic Granulomatous Disease), showed no case of BCGosis.

Conclusion: The BCG Moreau substrain vaccine, produced in Poland since 1955, showed genetic differences with its parental Brazilian substrain together with a superior clinical safety profile in comparison with the other BCG substrains, with no BCGosis in patients with IEI other than SCID and MSMD. Our data also confirmed significantly fewer cases of BCGosis and deaths caused by BCG infection in patients with SCID with this vaccine substrain. Finally, they confirmed the protecting role of NK cells, probably via their production of IFN-γ.

Keywords: BCG Moreau vaccine; BCG infection; Inborn Errors of Immunity; NK cells; disseminated BCG infection; susceptibility to BCG infection.

Copyright © 2022 Bernatowska, Pac, Heropolitańska-Pliszka, Pietrucha, Dąbrowska-Leonik, Skomska-Pawliszak, Bernat-Sitarz, Krzysztopa-Grzybowska, Wolska-Kuśnierz, Bohynikova, Augustynowicz, Augustynowicz-Kopeć, Korzeniewska-Koseła, Wieteska-Klimczak, Książyk, Jackowska, van den Burg, Casanova, Picard and Mikołuć.