Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable Antigen
Kuipers, Kirsten; Jong, Wouter S P; van der Gaast-de Jongh, Christa E; Houben, Diane; van Opzeeland, Fred; Simonetti, Elles; van Selm, Saskia; de Groot, Ronald; Koenders, Marije I.; Azarian, Taj; Pupo, Elder; van der Ley, Peter; Langereis, Jeroen D; Zomer, Aldert; Luirink, Joen; de Jonge, Marien I
(2017) Infection and Immunity, volume 85, issue 10
(Article)
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
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(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.
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Keywords: Administration, Intranasal, Animals, Antigens, Bacterial, Bacterial Outer Membrane Proteins, Bacterial Proteins, Computer Simulation, Cross Protection, Epitopes, Genes, MHC Class II, Heat-Shock Proteins, Interleukin-17, Lipopolysaccharides, Mice, Pneumococcal Infections, Pneumococcal Vaccines, Salmonella typhimurium, Secretory Vesicles, Streptococcus pneumoniae, Th17 Cells, Vaccination, Taverne
ISSN: 0019-9567
Publisher: American Society for Microbiology
Note: Copyright © 2017 American Society for Microbiology.
(Peer reviewed)