Outcomes of controlled human malaria infection after BCG vaccination

Jona Walk, L. Charlotte J. Bree, Wouter Graumans, Rianne Stoter, Geert-Jan Gemert, Marga Vegte-Bolmer, Karina Teelen, Cornelus C. Hermsen, Rob J. W. Arts, Marije C. Behet, Farid Keramati, Simone J. C. F. M. Moorlag, Annie S. P. Yang, Reinout Crevel, Peter Aaby, Quirijn Mast, André J. A. M. Ven, Christine Stabell Benn, Mihai G. Netea and Robert W. Sauerwein ()
Additional contact information
Jona Walk: Radboud University Medical Center, PO Box 9101
L. Charlotte J. Bree: Radboud University Medical Center PO Box 9101
Wouter Graumans: Radboud University Medical Center, PO Box 9101
Rianne Stoter: Radboud University Medical Center, PO Box 9101
Geert-Jan Gemert: Radboud University Medical Center, PO Box 9101
Marga Vegte-Bolmer: Radboud University Medical Center, PO Box 9101
Karina Teelen: Radboud University Medical Center, PO Box 9101
Cornelus C. Hermsen: Radboud University Medical Center, PO Box 9101
Rob J. W. Arts: Radboud University Medical Center PO Box 9101
Marije C. Behet: Radboud University Medical Center, PO Box 9101
Farid Keramati: Faculty of Science, Radboud university
Simone J. C. F. M. Moorlag: Radboud University Medical Center PO Box 9101
Annie S. P. Yang: Radboud University Medical Center, PO Box 9101
Reinout Crevel: Radboud University Medical Center PO Box 9101
Peter Aaby: Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut
Quirijn Mast: Radboud University Medical Center PO Box 9101
André J. A. M. Ven: Radboud University Medical Center PO Box 9101
Christine Stabell Benn: Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut
Mihai G. Netea: Radboud University Medical Center PO Box 9101
Robert W. Sauerwein: Radboud University Medical Center, PO Box 9101

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08659-3

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