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.