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
Stefan Magez,
Zeng Li,
Hang Thi Thu Nguyen,
Joar Esteban Pinto Torres,
Pieter Van Wielendaele,
Magdalena Radwanska,
Jakub Began,
Sebastian Zoll,
Yann G.-J. Sterckx
Affiliations
Stefan Magez
Laboratory of Cellular and Molecular Immunology, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
Zeng Li
Laboratory of Cellular and Molecular Immunology, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
Hang Thi Thu Nguyen
Laboratory of Cellular and Molecular Immunology, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
Joar Esteban Pinto Torres
Laboratory of Cellular and Molecular Immunology, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
Pieter Van Wielendaele
Laboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium
Magdalena Radwanska
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
Jakub Began
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
Sebastian Zoll
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
Yann G.-J. Sterckx
Laboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium
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.
