Tomatine adjuvantation of protective immunity to a major pre-erythrocytic vaccine candidate of malaria is mediated via CD8+ T cell release of IFN-gamma.

Karen G Heal,Andrew W Taylor-Robinson

doi:10.1155/2010/834326

Karen G Heal, Andrew W Taylor-Robinson

Open Access

https://doi.org/10.1155/2010/834326

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Abstract

The glycoalkaloid tomatine, derived from the wild tomato, can act as a powerful adjuvant to elicit an antigen-specific cell-mediated immune response to the circumsporozoite (CS) protein, a major pre-erythrocytic stage malaria vaccine candidate antigen. Using a defined MHC-class-I-restricted CS epitope in a Plasmodium berghei rodent model, antigen-specific cytotoxic T lymphocyte activity and IFN-γ secretion ex vivo were both significantly enhanced compared to responses detected from similarly stimulated splenocytes from naive and tomatine-saline-immunized mice. Further, through lymphocyte depletion it is demonstrated that antigen-specific IFN-γ is produced exclusively by the CD8+ T cell subset. We conclude that the processing of the P. berghei CS peptide as an exogenous antigen and its presentation via MHC class I molecules to CD8+ T cells leads to an immune response that is an in vitro correlate of protection against pre-erythrocytic malaria. Further characterization of tomatine as an adjuvant in malaria vaccine development is indicated.

Highlights

Adjuvants are immunogenic compounds that, when combined with an antigen, potentiate an antigen-specific immune response
Adjuvants may boost the response of an immunologically weak antigen and influence the type of immune response elicited [1]. While it has been know for many years that formulating antigen(s) with adjuvants may potentiate the magnitude of vaccineelicited immune response, traditionally accepted adjuvants such as alum and various oil-in-water emulsions have failed to induce cytotoxic T lymphocyte (CTL) responses
In the presence of homologous peptide (25 μg/mL), cells derived from P. berghei CS-immunized mice produced significantly raised peptide-specific CTL activity at 100–50 : 1 effector: target ratios compared to splenocytes from either tomatine-saline immunized mice (P < .025) or from naive controls (P < .05) (Table 1)

Summary

Introduction

Adjuvants are immunogenic compounds that, when combined with an antigen, potentiate an antigen-specific immune response. Adjuvants may boost the response of an immunologically weak antigen and influence the type of immune response elicited [1]. The adjuvant tomatine is based upon the glycoalkaloid lycopersicon (C50H83NO21), which is derived from the leaves and unripe fruit of the wilt-resistant wild tomato species Lycopersicon pimpinellifolium. This compound has been shown to have membrane-disrupting qualities [4, 5], similar in character to that of saponins which have long been established as potent immunostimulators [6].

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