Induction of Cytotoxic T Lymphocytes against the Plasmodium Falciparum Circumsporozoite Protein by Immunization with Soluble Recombinant Protein without Adjuvant
Abstract
Immunization of mice with irradiated malaria sporozoites induces protection that is dependent on CD8+ T cells, and adoptive transfer of CD8+ cytotoxic T lymphocyte (CTL) clones against rodent malaria circumsporozoite (CS) protein and sporozoite surface protein 2 completely protects against sporozoite challenge. Thus, there are now efforts to develop vaccines that induce CTL against the CS protein and sporozoite surface protein 2. Until recently, it was thought that induction of CTL required production of target proteins within cells, breakdown of the proteins to peptides in the cytoplasm, and transport of the peptides to the cell surface in combination with class I major histocompatibility complex molecules. It has now been shown that immunization with peptides in Freund's complete adjuvant and with soluble protein in liposomes can induce CTL. To determine whether we could induce CTL against the Plasmodium falciparum CS protein by immunization with soluble protein, B10.BR mice were immunized intravenously, intraperitoneally, or intramuscularly with a recombinant P. falciparum CS protein called RLF mixed with the adjuvant DETOX (monophosphoryl lipid A, cell wall skeleton of Mycobacteria phlei, and squalane) . Two weeks after the last dose, spleen cells from mice immunized intravenously, but not intraperitoneally or intramuscularly, had peptidespecific, major histocompatibility complex-restricted, CD8+ T-cell-dependent cytolytic activity against peptide 368-390 from the 7G8 P.falciparum CS protein.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1993
- Accession Number
- ADA276190
Entities
People
- Aditya Malik
- M. Gross
- S. L. Hoffman
- T. Ulrich
Organizations
- Naval Medical Research Center