Comparison of numerous delivery systems for the induction of cytotoxic T lymphocytes by immunization

Abstract

A variety of vaccine delivery systems including peptides with various adjuvants, recombinant particles, live recombinant viruses and bacteria and plasmid DNA were tested for their ability to induce CD8+ cytotoxic T lymphocytes (CTL) against a well-defined epitope (amino acids 252-260) from the circumsporozoite (CS) protein of Plasmodium berghei. We compared routes of immunization that would be applicable for the administration of a malaria vaccine in humans. The majority of these vaccines did not induce high CTL responses in the spleens of immunized mice. However, both a yeast-derived Ty virus-like particle expressing the optimal nine-amino acid epitope SYIPSAEKI from the CS protein (CSP-VLP) and a lipid-tailed peptide of this same sequence induced high levels of the major histocompatibility complex (MHC) class I-restricted CTL with one and three subcutaneous immunizations, respectively. Moreover, these CTL were able to recognize naturally processed antigen expressed by a recombinant vaccinia virus. The levels of CTL induced by CSP-VLP could be augmented by co-immunization with certain cytokines. Target cells pulsed with CSP-VLP were recognized and lysed, showing that the particles were effectively processed and presented through MHC class I presentation pathway. The levels of CTL induced using CSP-VLP and lipopeptides are comparable to those observed after immunization with multiple doses of irradiated sporozoites.

Th Cell-Independent Immune Responses to Chimeric Hemagglutinin/Simian Human Immunodeficiency Virus-Like Particles Vaccine

“…VLPs have also been proven to be potent CTL inducers compared with other vectors (21)(22)(23)(24). A study of PPV-VLPs immunization showed a safe and efficient strategy to induce CTLs and stimulate antiviral immunity in a CD4-independent manner (22).…”

Protective CD8+ T cell responses against the pre-erythrocytic stages of malaria parasites: an overview

“…However, high cell densities of responding T cells by sensitization either in vivo or in vitro with a short peptide could not easily be achieved , Valmori et al 1994, Allsopp et al 1996.…”

“…Immunization with Ty-VLP carrying a CD8 + T cell epitope of the P. berghei CS protein (TyPb) resulted in an immune response (Allsopp et al 1996). This study compared four adjuvants designed for the use with peptide, lipopeptides, recombinant salmonella, vaccinia virus and an attenuated vaccinia, plasmid DNA and Ty-VLPs.…”

Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8+ memory T cells

“…Sterile protection against sporozoite challenge can be transferred to naïve mice by CSP-specific CD8 + T cells [15][16][17][18]. There are several experimental vaccines described that successfully induce CSP-specific CD8 + T cells [19][20][21][22].…”

“…Sterile protection against sporozoite challenge can be transferred to naïve mice by CSP-specific CD8 + T cells [15][16][17][18]. There are several experimental vaccines described that successfully induce CSP-specific CD8 + T cells [19][20][21][22].In the present study we employed our previously described heterologous prime/boost vaccination strategy that is based on the induction of CD8 + T cells recognising a CSP-derived epitope of Plasmodium berghei presented by MHC class I [23]. Primary immunization is achieved with recombinant Salmonella.…”