Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses

Dung T Huynh; Emanuele Nolfi; Safia Guleed; Lobna Medfai; Natascha Wolf; Rienke F Uijen; Marien I de Jonge; Peter van Ulsen; Jes Dietrich; Joen Luirink; Alice J A M Sijts; Wouter S P Jong

doi:10.1016/j.biopha.2024.117563

Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses

Dung T Huynh, Emanuele Nolfi, Safia Guleed, Lobna Medfai, Natascha Wolf, Rienke F Uijen, Marien I de Jonge, Peter van Ulsen, Jes Dietrich, Joen Luirink, Alice J A M Sijts^*, Wouter S P Jong^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective C. trachomatis vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in Escherichia coli into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the C. trachomatis MOMP-derived CTH522-SP or HtrA antigen in mice. Intradermal administration of c-di-AMP-adjuvanted PB-CTH522-SP and PB-HtrA vaccines, produced in an LPS-detoxified E. coli strain, induced antigen-specific cellular immunity, as measured by significant release of IFN-γ and IL17a in draining cervical lymph node and splenic cell cultures. Moreover, significant induction of HtrA-specific IFN-γ expressing CD4 + and CD8 + T cells was detected in the spleens. While immunization with the two PB vaccines led to prominent levels of specific antibodies in both serum and vaginal compartments, only antiserum against PB-CTH522-SP exhibited C. trachomatis-specific neutralization activity. Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following C. trachomatis genital challenge. These data highlight the potential of the PB-based platform for the development of C. trachomatis vaccines.

Original language	English
Article number	117563
Journal	Biomedicine and Pharmacotherapy
Volume	180
Early online date	13 Oct 2024
DOIs	https://doi.org/10.1016/j.biopha.2024.117563
Publication status	Published - Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

DTH, EN, SG and LM received funding from the European Union\u2019s Horizon 2020 Research and Innovation Program under the Vacpath Marie Sk\u0142odowska-Curie Grant agreement No. 812915. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Wouter S. P. Jong reports financial support was provided by Abera Bioscience AB. Dung T. Huynh reports financial support was provided by Abera Bioscience AB. Natascha Wolf reports financial support was provided by Abera Bioscience AB. Joen Luirink reports financial support was provided by Abera Bioscience AB. Wouter S.P. Jong has patent #WO2018138316 pending to Abera Bioscience AB. Joen Luirink has patent #WO2018138316 pending to Abera Bioscience AB. Marien I. de Jonge is a member of the Advisory board of Abera Bioscience AB If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper DTH, EN, SG and LM received funding from the European Union's Horizon 2020 Research and Innovation Program under the Vacpath Marie Sk\u0142odowska-Curie Grant agreement No. 812915.

Funders	Funder number
Horizon 2020 Framework Programme
Abera Bioscience AB
Horizon 2020
Vacpath Marie Skłodowska-Curie	812915

Keywords

Chlamydia trachomatis
Intradermal administration
Protein bodies (PBs)
Vaccine development

UN SDGs

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

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10.1016/j.biopha.2024.117563Licence: CC BY

1-s2.0-S0753332224014495-mainFinal published version, 3.91 MBLicence: CC BY

Cite this

Huynh, D. T., Nolfi, E., Guleed, S., Medfai, L., Wolf, N., Uijen, R. F., de Jonge, M. I., van Ulsen, P., Dietrich, J., Luirink, J., Sijts, A. J. A. M., & Jong, W. S. P. (2024). Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses. Biomedicine and Pharmacotherapy, 180, Article 117563. https://doi.org/10.1016/j.biopha.2024.117563

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title = "Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses",

abstract = "Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective C. trachomatis vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in Escherichia coli into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the C. trachomatis MOMP-derived CTH522-SP or HtrA antigen in mice. Intradermal administration of c-di-AMP-adjuvanted PB-CTH522-SP and PB-HtrA vaccines, produced in an LPS-detoxified E. coli strain, induced antigen-specific cellular immunity, as measured by significant release of IFN-γ and IL17a in draining cervical lymph node and splenic cell cultures. Moreover, significant induction of HtrA-specific IFN-γ expressing CD4 + and CD8 + T cells was detected in the spleens. While immunization with the two PB vaccines led to prominent levels of specific antibodies in both serum and vaginal compartments, only antiserum against PB-CTH522-SP exhibited C. trachomatis-specific neutralization activity. Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following C. trachomatis genital challenge. These data highlight the potential of the PB-based platform for the development of C. trachomatis vaccines. ",

keywords = "Chlamydia trachomatis, Intradermal administration, Protein bodies (PBs), Vaccine development",

author = "Huynh, {Dung T} and Emanuele Nolfi and Safia Guleed and Lobna Medfai and Natascha Wolf and Uijen, {Rienke F} and {de Jonge}, {Marien I} and {van Ulsen}, Peter and Jes Dietrich and Joen Luirink and Sijts, {Alice J A M} and Jong, {Wouter S P}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

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doi = "10.1016/j.biopha.2024.117563",

language = "English",

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AU - Huynh, Dung T

AU - Nolfi, Emanuele

AU - Guleed, Safia

AU - Medfai, Lobna

AU - Wolf, Natascha

AU - Uijen, Rienke F

AU - de Jonge, Marien I

AU - van Ulsen, Peter

AU - Dietrich, Jes

AU - Luirink, Joen

AU - Sijts, Alice J A M

AU - Jong, Wouter S P

PY - 2024/11

Y1 - 2024/11

N2 - Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective C. trachomatis vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in Escherichia coli into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the C. trachomatis MOMP-derived CTH522-SP or HtrA antigen in mice. Intradermal administration of c-di-AMP-adjuvanted PB-CTH522-SP and PB-HtrA vaccines, produced in an LPS-detoxified E. coli strain, induced antigen-specific cellular immunity, as measured by significant release of IFN-γ and IL17a in draining cervical lymph node and splenic cell cultures. Moreover, significant induction of HtrA-specific IFN-γ expressing CD4 + and CD8 + T cells was detected in the spleens. While immunization with the two PB vaccines led to prominent levels of specific antibodies in both serum and vaginal compartments, only antiserum against PB-CTH522-SP exhibited C. trachomatis-specific neutralization activity. Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following C. trachomatis genital challenge. These data highlight the potential of the PB-based platform for the development of C. trachomatis vaccines.

AB - Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective C. trachomatis vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in Escherichia coli into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the C. trachomatis MOMP-derived CTH522-SP or HtrA antigen in mice. Intradermal administration of c-di-AMP-adjuvanted PB-CTH522-SP and PB-HtrA vaccines, produced in an LPS-detoxified E. coli strain, induced antigen-specific cellular immunity, as measured by significant release of IFN-γ and IL17a in draining cervical lymph node and splenic cell cultures. Moreover, significant induction of HtrA-specific IFN-γ expressing CD4 + and CD8 + T cells was detected in the spleens. While immunization with the two PB vaccines led to prominent levels of specific antibodies in both serum and vaginal compartments, only antiserum against PB-CTH522-SP exhibited C. trachomatis-specific neutralization activity. Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following C. trachomatis genital challenge. These data highlight the potential of the PB-based platform for the development of C. trachomatis vaccines.

KW - Chlamydia trachomatis

KW - Intradermal administration

KW - Protein bodies (PBs)

KW - Vaccine development

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DO - 10.1016/j.biopha.2024.117563

M3 - Article

C2 - 39405914

SN - 0753-3322

VL - 180

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

M1 - 117563

ER -

Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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