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Clin Infect Dis. 2019 Mar 28. pii: ciz246. doi: 10.1093/cid/ciz246. [Epub ahead of print]

INTERACTING NON-SPECIFIC IMMUNOLOGICAL EFFECTS OF BCG AND Tdapf VACCINATIONS: AN EXPLORATIVE RANDOMIZED TRIAL.

Author information

1
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, GA Nijmegen, The Netherlands.
2
Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
3
Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Odense, Denmark.
4
Section Pediatric Infectious Diseases and Radboud Center for Infectious Diseases (RCI), Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud university medical centre, GA Nijmegen, The Netherlands.

Abstract

BACKGROUND:

Certain vaccines such as BCG have non-specific effects, which modulate innate immune responses and lead to protection against mortality from unrelated infections (trained immunity). In contrast, in spite of the disease-specific effects, an enhanced overall mortality has been described after diphtheria-tetanus-pertussis (DTP) vaccination in females. This randomized trial aimed to investigate the non-specific immunological effects of BCG and DTP-containing vaccines on the immune response to unrelated pathogens.

METHODS:

Seventy-five healthy female adult volunteers were randomized to receive either BCG followed by a booster dose of tetanus-diphtheria-pertussis-inactivated polio vaccine (Tdap) 3 months later, BCG and Tdap combined, or Tdap followed by BCG 3 months later. Blood was collected before vaccination, as well as 1 and 4 days, 2 weeks and 3 months after the first vaccination(s), plus 2 weeks after the second vaccination. Ex-vivo leukocyte responses to unrelated stimuli and pathogens were assessed.

RESULTS:

Tdap vaccination led to short-term potentiation and long-term repression of monocyte-derived cytokine responses, and short-term as well as long-term repression of T-cell reactivity to unrelated pathogens. BCG led to short-term and long-term potentiation of monocyte-derived cytokine responses. When given together with Tdap or after Tdap, BCG abrogated the immunosuppressive effects of Tdap vaccination.

CONCLUSIONS:

Tdap induces immunotolerance to unrelated antigens, which is partially restored by concurrent or subsequent BCG vaccination. These data indicate that modulation of heterologous immune responses is induced by vaccination with Tdap and BCG, and more studies are warranted to investigate whether this is involved in the non-specific effects of vaccines on mortality.

KEYWORDS:

BCG; Tdap; heterologous immunity; trained immunity

PMID:
30919883
DOI:
10.1093/cid/ciz246

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