Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL registered adjuvant

• Published in: Vaccine 2002-09, Vol.20 (27), p.3292-3303
• Main Authors: Skeiky, Yasir AW, Coler, Rhea N, Brannon, Mark, Stromberg, Erika, Greeson, Kay, Thomas Crane, R, Campos-Neto, Antonio, Reed, Steven G
• Format: Article
• Language: English
• ISSN: 0264-410X
• DOI: 10.1016/S0264-410X(02)00302-X

Three immunodominant antigens (TSA, LmSTI1 and LeIF) previously identified in the context of host response to infection in infected donors and BALB/c mice, as well as their ability to elicit at least partial protection against infection in the BALB/c mouse model, were selected for inclusion into a subunit based vaccine. This is based on the premise that an effective vaccine against leishmaniasis (a complex parasitic infection) would require a multivalent cocktail of several antigens containing a broader range of protective epitopes that would cover a wide range of MHC types in a heterogeneous population. For practical considerations of vaccine development, we report on the generation of a single recombinant polyprotein comprising the sequences of all three open reading frames genetically linked in tandem. The resulting molecule, Leish-111f, comprises an open reading frame that codes for a 111kDa polypeptide. Evaluation of the immunogenicity and protective efficacy of Leish-111f formulated with IL-12 revealed that the immune responses to the individual components were maintained and as well, rLeish-111f protected BALB/c mice against infection to a magnitude equal or superior to those seen with any of the individual components of the vaccine construct or SLA, a soluble lysate. But because rIL-12 is expensive and difficult to manufacture and its efficacy and safety as an adjuvant for human use is questionable, we screened for other adjuvants that could potentially substitute for IL-12. We report that monophosphoryl lipid A (MPL) plus squalene (MPL-SE) formulated with rLeish-111f elicited protective immunity against infection. The demonstrated feasibility to manufacture a single recombinant vaccine comprising multiple protective open reading frames and the potential use of MPL-SE as a substitute for IL-12, takes us closer to the realization of an affordable and safe vaccine.