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Nat Commun. 2019 Feb 20;10(1):874. doi: 10.1038/s41467-019-08659-3.

Outcomes of controlled human malaria infection after BCG vaccination.

Author information

1
Department of Medical Microbiology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
2
Radboud Center for Infectious Diseases, Radboud University Medical Center PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
3
Department of Internal Medicine, Radboud University Medical Center PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
4
Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, 2300, Copenhagen, Denmark.
5
Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, 5000, Odense, Denmark.
6
Department of Molecular Biology, Faculty of Science, Radboud university, 6525 GA, Nijmegen, The Netherlands.
7
Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115, Bonn, Germany.
8
Department of Medical Microbiology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Robert.Sauerwein@Radboudumc.nl.
9
Radboud Center for Infectious Diseases, Radboud University Medical Center PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Robert.Sauerwein@Radboudumc.nl.

Abstract

Recent evidence suggests that certain vaccines, including Bacillus-Calmette Guérin (BCG), can induce changes in the innate immune system with non-specific memory characteristics, termed 'trained immunity'. Here we present the results of a randomised, controlled phase 1 clinical trial in 20 healthy male and female volunteers to evaluate the induction of immunity and protective efficacy of the anti-tuberculosis BCG vaccine against a controlled human malaria infection. After malaria challenge infection, BCG vaccinated volunteers present with earlier and more severe clinical adverse events, and have significantly earlier expression of NK cell activation markers and a trend towards earlier phenotypic monocyte activation. Furthermore, parasitemia in BCG vaccinated volunteers is inversely correlated with increased phenotypic NK cell and monocyte activation. The combined data demonstrate that BCG vaccination alters the clinical and immunological response to malaria, and form an impetus to further explore its potential in strategies for clinical malaria vaccine development.

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