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

doi:10.1128/IAI.00281-17

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^*

^*Corresponding author for this work

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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.

Original language	English
Article number	e00281-17
Pages (from-to)	1-13
Number of pages	13
Journal	Infection and Immunity
Volume	85
Issue number	10
Early online date	20 Sept 2017
DOIs	https://doi.org/10.1128/IAI.00281-17
Publication status	Published - Oct 2017

Funding

The work described in the manuscript was supported by Agentschap NL (Pneumo-Vac, no. 05 OM111009), Eurostars (PneumoNav, no. E9285), and the NIH (R01AI048935).

Funders	Funder number
National Institute of Allergy and Infectious Diseases	R01AI048935
Agentschap NL	05 OM111009

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/IAI.00281-17

Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable AntigenFinal published version, 1.92 MBLicence: Article 25fa Dutch Copyright Act

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Kuipers, K., Jong, W. S. P., van der Gaast-de Jongh, C. E., Houben, D., van Opzeeland, F., Simonetti, E., van Selm, S., de Groot, R., Koenders, M. I., Azarian, T., Pupo, E., van der Ley, P., Langereis, J. D., Zomer, A., Luirink, J., & de Jonge, M. I. (2017). Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen. Infection and Immunity, 85(10), 1-13. Article e00281-17. https://doi.org/10.1128/IAI.00281-17

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title = "Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen",

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, pp. 1-13. https://doi.org/10.1128/IAI.00281-17

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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.

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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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AN - SCOPUS:85029737478

SN - 0019-9567

VL - 85

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JO - Infection and Immunity

JF - Infection and Immunity

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ER -

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

Abstract

Funding

Keywords

UN SDGs

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