Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen

Kirsten Kuipers, Wouter S.P. Jong, Christa E. van der Gaast-de Jongh, Diane Houben, Fred van Opzeeland, Elles Simonetti, Saskia van Selm, Ronald de Groot, Marije I. Koenders, Taj Azarian, Elder Pupo, Peter van der Ley, Jeroen D. Langereis, Aldert Zomer, Joen Luirink, Marien I. de Jonge

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Article numbere00281-17
JournalInfection and Immunity
Volume85
Issue number10
DOIs
Publication statusPublished - 1 Jan 2017

Fingerprint

Cross Protection
Vaccination
Vaccines
Antigens
Salmonella enterica
Membranes
Interleukin-17
Streptococcus pneumoniae
Major Histocompatibility Complex
Computer Simulation
Polysaccharides
Lipopolysaccharides
Epitopes
Immunity
Serogroup
Proteins

Keywords

  • Antigen surface display
  • Autotransporter Hbp
  • Broad protection
  • Colonization
  • Intranasal vaccination
  • Protein antigens
  • PspA
  • Salmonella outer membrane vesicle (OMV)
  • Streptococcus pneumoniae
  • Th17

Cite this

Kuipers, K., Jong, W. S. P., van der Gaast-de Jongh, C. E., Houben, D., van Opzeeland, F., Simonetti, E., ... de Jonge, M. I. (2017). Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen. Infection and Immunity, 85(10), [e00281-17]. https://doi.org/10.1128/IAI.00281-17
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. / Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen. In: Infection and Immunity. 2017 ; Vol. 85, No. 10.
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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.",
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Kuipers, K, Jong, WSP, van der Gaast-de Jongh, CE, Houben, D, van Opzeeland, F, Simonetti, E, van Selm, S, de Groot, R, Koenders, MI, Azarian, T, Pupo, E, van der Ley, P, Langereis, JD, Zomer, A, Luirink, J & de Jonge, MI 2017, 'Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen' Infection and Immunity, vol. 85, no. 10, e00281-17. https://doi.org/10.1128/IAI.00281-17

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.

In: Infection and Immunity, Vol. 85, No. 10, e00281-17, 01.01.2017.

Research output: Contribution to JournalArticleAcademicpeer-review

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T1 - Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen

AU - Kuipers, Kirsten

AU - Jong, Wouter S.P.

AU - van der Gaast-de Jongh, Christa E.

AU - Houben, Diane

AU - van Opzeeland, Fred

AU - Simonetti, Elles

AU - van Selm, Saskia

AU - de Groot, Ronald

AU - Koenders, Marije I.

AU - Azarian, Taj

AU - Pupo, Elder

AU - van der Ley, Peter

AU - Langereis, Jeroen D.

AU - Zomer, Aldert

AU - Luirink, Joen

AU - de Jonge, Marien I.

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N2 - 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.

AB - 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.

KW - Antigen surface display

KW - Autotransporter Hbp

KW - Broad protection

KW - Colonization

KW - Intranasal vaccination

KW - Protein antigens

KW - PspA

KW - Salmonella outer membrane vesicle (OMV)

KW - Streptococcus pneumoniae

KW - Th17

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