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

Abstract

ObjectiveWe 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.MaterialWe 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.ResultsSignificantly 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.ConclusionThe 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.

National experience with adenosine deaminase deficiency related SCID in Polish children

“…Serious complications in IEI patients are only observed in SCID, especially associated with low NK cell numbers, and patients with Mendelian susceptibility to mycobacterial diseases (MSMD). NK cells are thought to have a protective role probably due to IFN-g production (11). However, none of our patients with ADA-SCID demonstrated a disseminated BCG disease, with local manifestations observed in total in 3 patients, one before ERT and two after initiation of ERT and with an increase in the number of lymphocytes, treated with antimycobacterial double therapy (isoniazid, rifampicin) (Figure 2; Table 3).…”

“…Another issue that needs addressing here, is the post-BCG vaccination disease in an IEI patient (11). In Poland, vaccination against tuberculosis is obligatory in the first two days of life in all newborns, unless they have contraindications.…”