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Infect Immun. 2017 Sep 20;85(10). pii: e00281-17. doi: 10.1128/IAI.00281-17. Print 2017 Oct.

Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable Antigen.

Author information

1
Laboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Abera Bioscience AB, Stockholm, Sweden.
3
Section Molecular Microbiology, Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University, Amsterdam, The Netherlands.
4
Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Center for Communicable Diseases Dynamics, Department of Epidemiology, Harvard University, Boston, Massachusetts, USA.
6
Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.
7
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
8
Laboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands marien.dejonge@radboudumc.nl.

Abstract

Serotype-specific protection against Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from Salmonella enterica serovar Typhimurium displaying the variable N terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on in silico prediction combined with ex vivo screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.

KEYWORDS:

PspA; Salmonella outer membrane vesicle (OMV); Streptococcus pneumoniae; Th17; antigen surface display; autotransporter Hbp; broad protection; colonization; intranasal vaccination; protein antigens

PMID:
28717032
PMCID:
PMC5607416
DOI:
10.1128/IAI.00281-17
[Indexed for MEDLINE]
Free PMC Article

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