title: Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis.
abstract: Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe of which is visceral leishmaniasis (VL). Vaccination will likely provide the most effective long-term control strategy, as the large number of vectors and potential infectious reservoirs renders sustained interruption of Leishmania parasite transmission extremely difficult. Selection of the best vaccine is complicated because, although several vaccine antigen candidates have been proposed, they have emerged following production in different platforms. To consolidate the information that has been generated into a single vaccine platform, we expressed seven candidates as recombinant proteins in E. coli. After verifying that each recombinant protein could be recognized by VL patients, we evaluated their protective efficacy against experimental L. donovani infection of mice. Administration in formulation with the Th1-potentiating adjuvant GLA-SE indicated that each antigen could elicit antigen-specific Th1 responses that were protective. Considering the ability to reduce parasite burden along with additional factors such as sequence identity across Leishmania species, we then generated a chimeric fusion protein comprising a combination of the 8E, p21 and SMT proteins. This E. coli -expressed fusion protein was also demonstrated to protect against L. donovani infection. These data indicate a novel recombinant vaccine antigen with the potential for use in VL control programs.
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA. Electronic address: mduthie@idri.org.
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Favila
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Hofmeyer
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Yeung L
authors.initials: YL
authors.lastname: Tutterrow
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reed
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Laurance
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Picone
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Guderian
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: H Remy
authors.initials: HR
authors.lastname: Bailor
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Aarthy C
authors.initials: AC
authors.lastname: Vallur
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Raodoh
authors.initials: R
authors.lastname: Mohamath
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Vergara
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Randall F
authors.initials: RF
authors.lastname: Howard
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic
keywords: Leishmania; Protein; Protozoa; T cell; Vaccine