A heterologous prime-boost vaccination regimen using ORFF DNA and recombinant ORFF protein confers protective immunity against experimental visceral Leishmaniasis

Abstract

Objective. We describe the effectiveness of a prime-boost vaccination regimen using the open-reading frame (ORFF) gene from the LD1 locus of Leishmania donovani. Methods. A group of BALB/c mice was immunized with the plasmid carrying the gene for ORFF (F/pcDNA 3.1) and given a booster dose of either the same DNA vaccine or a vaccine with a recombinant ORFF (rORFF) protein. Another group of BALB/c mice was immunized and given a booster dose of the rORFF protein vaccine. The protective efficacies of these vaccine formulations were compared after challenge with L. donovani stationary-phase promastigotes. Results. Mice given the prime-boost vaccination regimen had an enhanced reduction in parasite load (75%-80%), compared with that in mice given only the rORFF protein vaccine (45%-60%). However, the protective response induced in the prime-boost group was not more than that elicited in the DNA vaccine group. Immunization with only the rORFF protein vaccine did not induce the typical T helper response, whereas priming with the DNA vaccine resulted in enhanced production of immunoglobulin G2a and interferon-γ. Furthermore, priming with the DNA vaccine also led to enhanced proliferation of splenocytes, suggesting subsequent expansion of antigen-specific T cells. Conclusions. The heterologous prime-boost vaccination strategy may be utilized for visceral leishmaniasis. © 2005 by the Infectious Diseases Society of America. All rights reserved.