title: Identification of Leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates.
abstract: Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver and bone marrow lesions and excreted in the patients' urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1) and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in Escherichia coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2+ BpMPLA-SE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to VL and opens novel possibilities for vaccine development to other serious infectious diseases.
authors.affiliation: The Forsyth Institute, Cambridge, MA 02142, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Kashino
authors.forename: C
authors.initials: C
authors.lastname: Abeijon
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: K A
authors.initials: KA
authors.lastname: Kanunfre
authors.forename: F S
authors.initials: FS
authors.lastname: Kubrusly
authors.forename: F O
authors.initials: FO
authors.lastname: Silva
authors.forename: D L
authors.initials: DL
authors.lastname: Costa
authors.forename: D
authors.initials: D
authors.lastname: Campos
authors.forename: C H N
authors.initials: CH
authors.lastname: Costa
authors.forename: I
authors.initials: I
authors.lastname: Raw
authors.forename: A
authors.initials: A
authors.lastname: Campos-Neto
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006801:Humans; D007893:Leishmania donovani / Q000737:chemistry / Q000276:immunology*; D018314:Leishmania infantum / Q000737:chemistry / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D013058:Mass Spectrometry; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D013154:Spleen / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology; D014556:Urine / Q000737:chemistry; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D014614:Vaccines, Synthetic