title: Exacerbated Leishmaniasis Caused by a Viral Endosymbiont can be Prevented by Immunization with Its Viral Capsid.
abstract: Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as a potent innate immunogen, aggravating lesional inflammation and development in mice. In humans, the presence of LRV in Leishmania guyanensis and in L. braziliensis was significantly correlated with poor treatment response and symptomatic relapse. So far, no clinical effort has used LRV for prophylactic purposes. In this context, we designed an original vaccine strategy that targeted LRV nested in Leishmania parasites to prevent virus-related complications. To this end, C57BL/6 mice were immunized with a recombinant LRV1 Leishmania guyanensis viral capsid polypeptide formulated with a T helper 1-polarizing adjuvant. LRV1-vaccinated mice had significant reduction in lesion size and parasite load when subsequently challenged with LRV1+ Leishmania guyanensis parasites. The protection conferred by this immunization could be reproduced in naïve mice via T-cell transfer from vaccinated mice but not by serum transfer. The induction of LRV1 specific T cells secreting IFN-γ was confirmed in vaccinated mice and provided strong evidence that LRV1-specific protection arose via a cell mediated immune response against the LRV1 capsid. Our studies suggest that immunization with LRV1 capsid could be of a preventive benefit in mitigating the elevated pathology associated with LRV1 bearing Leishmania infections and possibly avoiding symptomatic relapses after an initial treatment. This novel anti-endosymbiotic vaccine strategy could be exploited to control other infectious diseases, as similar viral infections are largely prevalent across pathogenic pathogens and could consequently open new vaccine opportunities.
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Patrik
authors.initials: P
authors.lastname: Castiglioni
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Hartley
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Prevel
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Chantal
authors.initials: C
authors.lastname: Desponds
authors.affiliation: Swiss Vaccine Research Institute, Epalinges, Switzerland.|Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Utzschneider
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Remzi-Onur
authors.initials: RO
authors.lastname: Eren
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Haroun
authors.initials: H
authors.lastname: Zangger
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Livia
authors.initials: L
authors.lastname: Brunner
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Collin
authors.affiliation: Swiss Vaccine Research Institute, Epalinges, Switzerland.|Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.|Department of Medicine, Division of Infectious Disease, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: F Matthew
authors.initials: FM
authors.lastname: Kuhlmann
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beverley
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Nicolas
authors.identifier: 0000-0003-0136-7245
authors.initials: N
authors.lastname: Fasel
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ronet
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D018334:Leishmania guyanensis / Q000235:genetics / Q000276:immunology / Q000502:physiology / Q000821:virology*; D007896:Leishmaniasis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D019199:Leishmaniavirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013559:Symbiosis; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D036022:Capsid Proteins