Potentiation by a novel alkaloid glycoside adjuvant of a protective cytotoxic T cell immune response specific for a preerythrocytic malaria vaccine candidate antigen.

Abstract

We have recently demonstrated that the novel glycoalkaloid tomatine, derived from leaves of the wild tomato Lycopersicon pimpinellifolium, can act as a powerful adjuvant for the elicitation of antigen-specific CD8+ T cell responses. Here, we have extended our previous investigation with the model antigen ovalbumin to an established malaria infection system in mice and evaluated the cellular immune response to a major preerythrocytic stage malaria vaccine candidate antigen when administered with tomatine. The defined MHC H-2kd class I-binding 9-mer peptide (amino acids 252-260) from Plasmodium berghei circumsporozoite (CS) protein was prepared with tomatine to form a molecular aggregate formulation and this used to immunise BALB/c (H-2kd) mice. Antigen-specific IFN-gamma secretion and cytotoxic T lymphocyte activity in vitro were both significantly enhanced compared to responses detected from similarly stimulated splenocytes from naive and tomatine-saline-immunised control mice. Moreover, when challenged with P. berghei sporozoites, mice immunised with the CS 9-mer-tomatine preparation had a significantly delayed onset of erythrocytic infection compared to controls. The data presented validate the use of tomatine to potentiate a cellular immune response to antigenic stimulus by testing in an important biologically relevant system. Specifically, the processing of the P. berghei CS 9-mer as an exogenous antigen and its presentation via MHC class I molecules to CD8+ T cells led to an immune response that is an in vitro correlate of protection against preerythrocytic malaria. This was confirmed by the protective capacity of the 9-mer-tomatine combination upon in vivo immunisation. These findings merit further work to optimise the use of tomatine as an adjuvant in malaria vaccine development.

• Authors: K G Heal, N A Sheikh, M R Hollingdale, W J Morrow, A W Taylor-Robinson
• Journal: Vaccine (Vaccine) Vol. 19 Issue 30 Pg. 4153-61 (Jul 20 2001) ISSN: 0264-410X [Print] Netherlands
• PMID: 11457540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Cytokines
• Malaria Vaccines
• Protozoan Proteins
• circumsporozoite protein, Protozoan
• Tomatine

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Cytokines (biosynthesis)
• Malaria Vaccines (immunology)
• Mice
• Mice, Inbred BALB C
• Plasmodium berghei (immunology)
• Protozoan Proteins (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tomatine (administration & dosage)
• Vaccination