The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples

Magez, Stefan; Li, Zeng; Nguyen, Hang Thi Thu; Pinto Torres, Joar Esteban; Van Wielendaele, Pieter; Radwanska, Magdalena; Began, Jakub; Zoll, Sebastian; Sterckx, Yann G.-J.

doi:10.3390/pathogens10081050

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The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples

by

Stefan Magez

^1,2,3,*

,

Zeng Li

^1,4,

Hang Thi Thu Nguyen

^1,2,3

,

Joar Esteban Pinto Torres

¹,

Pieter Van Wielendaele

⁴

,

Magdalena Radwanska

^3,5,

Jakub Began

^6,†,

Sebastian Zoll

^6,‡

and

Yann G.-J. Sterckx

^4,‡

¹

Laboratory of Cellular and Molecular Immunology, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium

²

Department of Biochemistry and Microbiology, Ghent University, Ledeganckstraat 35, 9000 Ghent, Belgium

³

Laboratory for Biomedical Research, Department of Molecular Biotechnology, Environment Technology and Food Technology, Ghent University Global Campus, Songdomunhwa-Ro 119-5, Yeonsu-Gu, Incheon 406-840, Korea

⁴

Laboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium

⁵

Department of Biomedical Molecular Biology, Ghent University, Technologiepark Zwijnaarde 71, 9000 Ghent, Belgium

⁶

Laboratory of Structural Parasitology, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo Namesti 2, 16610 Prague 6, Czech Republic

^*

Author to whom correspondence should be addressed.

^†

Present address: Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.

^‡

These authors contributed equally to this work and should be considered joint last authors.

Pathogens 2021, 10(8), 1050; https://doi.org/10.3390/pathogens10081050

Submission received: 15 July 2021 / Revised: 2 August 2021 / Accepted: 10 August 2021 / Published: 19 August 2021

(This article belongs to the Special Issue Immunity and Vaccine Development Efforts against Trypanosomatid Parasites)

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Abstract

Salivarian trypanosomes comprise a group of extracellular anthroponotic and zoonotic parasites. The only sustainable method for global control of these infection is through vaccination of livestock animals. Despite multiple reports describing promising laboratory results, no single field-applicable solution has been successful so far. Conventionally, vaccine research focusses mostly on exposed immunogenic antigens, or the structural molecular knowledge of surface exposed invariant immunogens. Unfortunately, extracellular parasites (or parasites with extracellular life stages) have devised efficient defense systems against host antibody attacks, so they can deal with the mammalian humoral immune response. In the case of trypanosomes, it appears that these mechanisms have been perfected, leading to vaccine failure in natural hosts. Here, we provide two examples of potential vaccine candidates that, despite being immunogenic and accessible to the immune system, failed to induce a functionally protective memory response. First, trypanosomal enolase was tested as a vaccine candidate, as it was recently characterized as a highly conserved enzyme that is readily recognized during infection by the host antibody response. Secondly, we re-addressed a vaccine approach towards the Invariant Surface Glycoprotein ISG75, and showed that despite being highly immunogenic, trypanosomes can avoid anti-ISG75 mediated parasitemia control.

Keywords: trypanosomosis; vaccination; enolase; ISG75

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MDPI and ACS Style

Magez, S.; Li, Z.; Nguyen, H.T.T.; Pinto Torres, J.E.; Van Wielendaele, P.; Radwanska, M.; Began, J.; Zoll, S.; Sterckx, Y.G.-J. The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples. Pathogens 2021, 10, 1050. https://doi.org/10.3390/pathogens10081050

AMA Style

Magez S, Li Z, Nguyen HTT, Pinto Torres JE, Van Wielendaele P, Radwanska M, Began J, Zoll S, Sterckx YG-J. The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples. Pathogens. 2021; 10(8):1050. https://doi.org/10.3390/pathogens10081050

Chicago/Turabian Style

Magez, Stefan, Zeng Li, Hang Thi Thu Nguyen, Joar Esteban Pinto Torres, Pieter Van Wielendaele, Magdalena Radwanska, Jakub Began, Sebastian Zoll, and Yann G.-J. Sterckx. 2021. "The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples" Pathogens 10, no. 8: 1050. https://doi.org/10.3390/pathogens10081050

APA Style

Magez, S., Li, Z., Nguyen, H. T. T., Pinto Torres, J. E., Van Wielendaele, P., Radwanska, M., Began, J., Zoll, S., & Sterckx, Y. G.-J. (2021). The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples. Pathogens, 10(8), 1050. https://doi.org/10.3390/pathogens10081050

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The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples

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