A protein particle vaccine containing multiple malaria epitopes

Abstract

Ty virus-like particles consist of a single protein species that can be produced in yeast. Recombinant Ty-VLPs carrying a string of up to 15 defined cytotoxic T lymphocyte (CTL) epitopes from Plasmodium species prime protective CTL responses in mice following a single administration without adjuvant. Effective processing of epitopes from the string was demonstrated in vitro and in vivo and was not affected by flanking sequences.

ASSOCIATION OF INTERFERON-γ RESPONSES TO PRE-ERYTHROCYTIC STAGE VACCINE CANDIDATE ANTIGENS OF PLASMODIUM FALCIPARUM IN YOUNG KENYAN CHILDREN WITH IMPROVED HEMOGLOBIN LEVELS: XV. ASEMBO BAY COHORT PROJECT

“…These results suggest that the peptide pool from single antigen might induce weaker immune responses compared with that from multiple antigens, which lends support to the approach of including several well-characterized peptides from different antigens in a multivalent, multistage vaccines for optimum responses. 10,15 Because of the limited cell numbers in the small volumes of blood collected from children, we were unable to conduct a T cell subset depletion assay to determine the cellular source of IFN-␥ in this study. It is known that most of pre-erythrocytic stage T cell epitopes used in this study are degenerate cytotoxic CD8 + T cell epitopes restricted by multiple HLA-A and HLA-B class I supertype alleles.…”

“…14 Another study in mice using multiple malaria CD8 + T cell epitope vaccine formulations also showed that protection correlated with high levels of IFN-␥-secreting cells. 15 In addition, a study in humans reported a positive correlation between preerythrocytic stage specific IFN-␥ secretion and CTL responses in volunteers immunized with irradiated sporozoites. 5 More recently, several studies conducted in different malariaendemic regions have highlighted an association between liver stage antigen-1 (LSA-1)−driven IFN-␥ or IL-10 responses and P. falciparum infection/morbidity.…”

Influence of flanking sequences on presentation efficiency of a CD8+ cytotoxic T-cell epitope delivered by parvovirus-like particles

“…In various systems, either replicative such as vaccinia or non-replicative such as VLPs produced in yeast (Ty VLPs) (Gilbert et al, 1997) or bacterial toxins reaching the cytosol of APCs (Fayolle et al, 2001), the use of polyepitope chains containing multiple CD8 + T-cell epitopes has been reported for vaccine design (Thomson et al, 1995;Woodberry et al, 1999). In these studies, no influence of the flanking sequences was observed, since the epitopes were linked together and all seemed to be correctly processed.…”

“…Although it was initially established that some flanking sequences could prevent the proteolytic generation of the epitope (Del Val et al, 1991), it is not clear whether the presence of natural flanking sequences is necessary for the correct cleavage of the epitope. In fact, several studies have demonstrated the efficient presentation of CTL epitopes regardless of their context (Gilbert et al, 1997;Thomson et al, 1995).…”

Alternating vector immunizations encoding pre‐erythrocytic malaria antigens enhance memory responses in a malaria endemic area

“…These were ME-TRAP, encoding the pre-erythrocytic antigen TRAP, and CS. TRAP is coupled to the multiple epitope (ME) string [23]. This contains 14 MHC class I epitopes from pre-erythrocytic antigens, three class II epitopes (from BCG, tetanus toxin and the Circumsporozoite antigen), two pre-erythrocytic B cell epitopes and pb9 (a Plasmodium berghei T cell epitope that allows pre-clinical potency and stability testing).…”