Long synthetic peptides encompassing the Plasmodium falciparum LSA3 are the target of human B and T cells and are potent inducers of B helper, T helper and cytolytic T cell responses in mice

We synthesized 17 long synthetic peptides (LSP) spanning the whole 200-kDa Plasmodium falciparum liver stage antigen-3 (LSA3), an antigen that induces protection in chimpanzee, and analyzed their immunogenicity in BALB/c mice and their antigenicity in individuals living in a hyper-endemic malaria ar ea. Our findings show that both specific antibodies and T cell proliferatio n against most LSA3-LSP develop in malaria-exposed adults. All individuals studied had detectable antibodies against a minimum: of 8 and a maximum of 15 polypeptides. it is noteworthy that antibody prevalence and titers were as high against non-repeat as repeat regions. Although the extent of T cell reactivity was lower than that observed for B cells, most of the sequences contained at least one. T helper epitope, indicating that the majority of LSA3-LSP contain both B and T cell epitopes within the same sequence. Injec tion, of LSA3-LSP with SBSA2 adjuvant in mice, showed strong immunogenicity for most of them, eliciting both T cell responses and specific antibody pr oduction. While all the peptides were immunogenic for B: cells, different p atterns of T cell responses were induced. These peptides were thus classifi ed in three sets according to the levels of the T cell proliferative and of the IFN-gamma -specific responses. importantly, antibodies and T cells aga inst some of the LSP were able to: recognize LSA3 native protein on P. falc iparum sporozoites. Additionally, some LSP (44-119, 1026-1095, 1601.-1712): also contained epitopes recognized by H-2(d) class I-restricted T cells. T hese results led to the identification of numerous domains that are highly antigenic and immunogenic within the LSA3: protein, and underline the value of the LSP approach for vaccine development.