Outcomes of controlled human malaria infection after BCG vaccination

被引：184

作者：

Walk, Jona ^{[1
,2
]}

de Bree, L. Charlotte J. ^{[2
,3
,4
,5
]}

Graumans, Wouter ^{[1
,2
]}

Stoter, Rianne ^{[1
,2
]}

van Gemert, Geert-Jan ^{[1
,2
]}

van de Vegte-Bolmer, Marga ^{[1
,2
]}

Teelen, Karina ^{[1
,2
]}

Hermsen, Cornelus C. ^{[1
,2
]}

Arts, Rob J. W. ^{[2
,3
]}

Behet, Marije C. ^{[1
,2
]}

Keramati, Farid ^{[6
]}

Moorlag, Simone J. C. F. M. ^{[2
,3
]}

Yang, Annie S. P. ^{[1
,2
]}

van Crevel, Reinout ^{[2
,3
]}

Aaby, Peter ^{[4
]}

de Mast, Quirijn ^{[2
,3
]}

van der Ven, Andre J. A. M. ^{[2
,3
]}

Benn, Christine Stabell ^{[4
,5
]}

Netea, Mihai G. ^{[2
,3
,7
]}

Sauerwein, Robert W. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, POB 9101, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Radboud Ctr Infect Dis, Med Ctr, POB 9101, NL-6500 HB Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, POB 9101, NL-6500 HB Nijmegen, Netherlands

[4] Statens Serum Inst, Band Hlth Project, Res Ctr Vitamins & Vaccines, DK-2300 Copenhagen, Denmark

[5] Univ Southern Denmark, Odense Univ Hosp, Odense Patient Data Explorat Network, DK-5000 Odense, Denmark

[6] Radboud Univ Nijmegen, Fac Sci, Dept Mol Biol, NL-6525 GA Nijmegen, Netherlands

[7] Univ Bonn, Life & Med Sci Inst LIMES, Dept Genom & Immunoregulat, D-53115 Bonn, Germany

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

INNATE IMMUNE-RESPONSES; NONSPECIFIC PROTECTION; PLASMODIUM; MEMORY; CELLS; REVACCINATION; REINFECTION; VOLUNTEERS; SURVIVAL;

D O I：

10.1038/s41467-019-08659-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recent evidence suggests that certain vaccines, including Bacillus-Calmette Guerin (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.

引用

页数：8

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