Exacerbated Leishmaniasis Caused by a Viral Endosymbiont can be Prevented by Immunization with Its Viral Capsid

• Published in: PLoS neglected tropical diseases Vol. 11; no. 1; p. e0005240
• Main Authors: Castiglioni, Patrik, Hartley, Mary-Anne, Rossi, Matteo, Prevel, Florence, Desponds, Chantal, Utzschneider, Daniel T, Eren, Remzi-Onur, Zangger, Haroun, Brunner, Livia, Collin, Nicolas, Zehn, Dietmar, Kuhlmann, F Matthew, Beverley, Stephen M, Fasel, Nicolas, Ronet, Catherine
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.01.2017; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Capsid Proteins - administration & dosage; Capsid Proteins - genetics; Capsid Proteins - immunology; Care and treatment; Colleges & universities; Cytokines; Dosage and administration; Female; Funding; Humans; Immune response; Immunity, Cellular; Immunization; Immunology; Infections; Infectious diseases; Inflammation; Leishmania guyanensis - genetics; Leishmania guyanensis - immunology; Leishmania guyanensis - physiology; Leishmania guyanensis - virology; Leishmaniasis; Leishmaniasis - immunology; Leishmaniasis - parasitology; Leishmaniasis - prevention & control; Leishmaniavirus - genetics; Leishmaniavirus - immunology; Leishmaniavirus - physiology; Lymphocytes; Medical research; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Parasites; Parasitic diseases; Pathogens; Research and Analysis Methods; Software; Symbiosis; T cells; T-Lymphocytes - immunology; Tropical diseases; Vaccination; Vaccines; Vector-borne diseases; Viral infections; Viruses; United States > US; Switzerland; Missouri
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0005240

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.