Bacillus Calmette-Guérin vaccination induces a trained innate immunity phenotype in adults over 50 years of age: A randomized trial in Guinea-Bissau.

Autor: Berendsen MLT; Bandim Health Project, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Studiestræde 6, 1455 Copenhagen C, Denmark; Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands. Electronic address: Mike.Berendsen@radboudumc.nl., Bles P; Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands., de Bree LCJ; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands., Jensen KJ; Bandim Health Project, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Studiestræde 6, 1455 Copenhagen C, Denmark; Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Ørsteds Plads 345C, 2800 Kgs Lyngby, Denmark; Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark., Jensen CC; Bandim Health Project, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Studiestræde 6, 1455 Copenhagen C, Denmark., Wejse C; GloHAU Center for Global Health, Department of Public Health, Aarhus University, Bartholins Allé 2, 8000 Aarhus, Denmark; Department of Infectious Diseases, Skejby University Hospital, Palle Juul-Jensens Blvd. 99, 8200 Aarhus, Denmark., Mendes DV; Hospital Raoul Follereau, Bissau, Guinea-Bissau., Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands; Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany; Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Strada Petru Rareș 2, Craiova 200349, Romania., Benn CS; Bandim Health Project, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Studiestræde 6, 1455 Copenhagen C, Denmark; Danish Institute for Advanced Study, University of Southern Denmark, Fioniavej 34, 5230 Odense, Denmark.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Oct 17; Vol. 42 (26), pp. 126439. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1016/j.vaccine.2024.126439
Abstrakt: Background: The beneficial effects of Bacillus Calmette-Guérin (BCG) as an intervention against non-mycobacterial infections have been extensively studied in randomized trials. These non-specific effects have been linked to a heterologous increase of pro-inflammatory cytokine production by innate immune cells. It is unknown if BCG induces such responses in older individuals from TB-endemic countries.
Methods: In a single-blinded trial in Guinea-Bissau, 40 adults over 50 years of age were randomized 1:1 in a block of 40 to intradermal injection of BCG-Japan (intervention) or solvent (placebo). Production of interleukin (IL)-1β, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was measured by ELISA in supernatant of peripheral blood mononuclear cells stimulated with Mycobacterium tuberculosis and heterologous pathogens. The trial was registered at clinicaltrials.gov (NCT02953327).
Findings: Between January 25 and March 7, 2017, 40 individuals were randomized. Two months after vaccination, BCG-Japan recipients (n = 11) had higher production of IFN-γ to M. tuberculosis stimulation (Geometric mean ratio (GMR): 3·91 [95 % Confidence Interval (CI), 1·53-9·96]) and increased release of the pro-inflammatory innate cytokines IL-1β, IL-6 and TNF-α to non-specific stimuli (GMR TNF-α: 1·47 [95 % CI, 0·98-2·19]) than their controls (n = 13). Both the specific and non-specific responses were more pronounced among those with a positive QuantiFERON at baseline.
Interpretation: BCG-Japan can induce a trained immunity phenotype in older adults. These effects were particularly strong in previously M. tuberculosis exposed individuals. Future randomized trials are needed to determine BCG's potential to protect the older populations from infections-driven morbidity and mortality.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christine Stabell Benn reports financial support was provided by Danish National Research Foundation. Christine Stabell Benn reports financial support was provided by European Research Council. Mihai Netea reports financial support was provided by European Research Council. Mihai Netea reports financial support was provided by Royal Netherlands Academy of Arts and Sciences. Christian Wejse reports a relationship with Danish National Board of Patient Safety that includes: consulting or advisory. Christian Wejse reports a relationship with Novartis that includes: speaking and lecture fees.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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