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Nat Commun. 2019 Jul 5;10(1):2981. doi: 10.1038/s41467-019-10814-9.

Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine.

Author information

1
Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Lundlaan 6, Utrecht, 3584 EA, The Netherlands.
2
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
3
Medical Research Council/University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
4
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, United Kingdom.
5
Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Lundlaan 6, Utrecht, 3584 EA, The Netherlands. D.Bogaert@ed.ac.uk.
6
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. D.Bogaert@ed.ac.uk.
7
Medical Research Council/University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom. D.Bogaert@ed.ac.uk.

Abstract

Streptococcus pneumoniae is the main bacterial pathogen involved in pneumonia. Pneumococcal acquisition and colonization density is probably affected by viral co-infections, the local microbiome composition and mucosal immunity. Here, we report the interactions between live-attenuated influenza vaccine (LAIV), successive pneumococcal challenge, and the healthy adult nasal microbiota and mucosal immunity using an experimental human challenge model. Nasal microbiota profiles at baseline are associated with consecutive pneumococcal carriage outcome (non-carrier, low-dense and high-dense pneumococcal carriage), independent of LAIV co-administration. Corynebacterium/Dolosigranulum-dominated profiles are associated with low-density colonization. Lowest rates of natural viral co-infection at baseline and post-LAIV influenza replication are detected in the low-density carriers. Also, we detected the fewest microbiota perturbations and mucosal cytokine responses in the low-density carriers compared to non-carriers or high-density carriers. These results indicate that the complete respiratory ecosystem affects pneumococcal behaviour following challenge, with low-density carriage representing the most stable ecological state.

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