Immunization with a polyprotein vaccine consisting of the T-Cell antigens thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and Leishmania elongation initiation factor protects against leishmaniasis.
Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.
Infectious Disease Research Institute, Seattle, Washington 98104, USA. coler@idri.org
Rhea N
RN
Coler
Yasir A W
YA
Skeiky
Karen
K
Bernards
Kay
K
Greeson
Darrick
D
Carter
Charisa D
CD
Cornellison
Farrokh
F
Modabber
Antonio
A
Campos-Neto
Steven G
SG
Reed
D000276:Adjuvants, Immunologic; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000975:Antioxidants; D017358:Cell Wall Skeleton; D003311:Cord Factors; D004195:Disease Models, Animal; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D008050:Lipid A / Q000031:analogs & derivatives*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology*; D010448:Peptide Initiation Factors / Q000235:genetics / Q000276:immunology*; D010544:Peroxidases / Q000235:genetics / Q000276:immunology*; D054464:Peroxiredoxins; D020815:Polyproteins / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D000975:Antioxidants; D017358:Cell Wall Skeleton; D003311:Cord Factors; D006360:Heat-Shock Proteins; C092810:LeIF protein, Leishmania; D008050:Lipid A; D018832:Molecular Chaperones; D010448:Peptide Initiation Factors; D020815:Polyproteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C075897:Ribi adjuvant; C489791:Stip1 protein, mouse; D014614:Vaccines, Synthetic; D010544:Peroxidases; D054464:Peroxiredoxins; C048436:monophosphoryl lipid A