title: A strong CD8+ T cell response is elicited using the synthetic polypeptide from the C-terminus of the circumsporozoite protein of Plasmodium berghei together with the adjuvant QS-21: quantitative and phenotypic comparison with the vaccine model of irradiated sporozoites.
abstract: Stable protective immunity can be achieved against malaria by the injection of radiation-attenuated sporozoites (gamma-spz) and is mediated by IFN-gamma producing CD8+ T cells targeting the pre-erythrocytic stages. An efficient malaria vaccine should mimic this immunity. We compared the immune response specific for the circumsporozoite protein (CSP) of Plasmodium berghei (P. berghei), an important target of this protective response, elicited in mice immunized with the long synthetic polypeptide (LSP) PbCS 242-310, representing the C-terminus of the CSP of P. berghei, with the adjuvant QS-21 or injected with gamma-spz. The ex vivo evaluation of the CD8+ T cell response by IFN-gamma ELISPOT assay revealed that the injection of LSP with QS-21 induced, compared to gamma-spz, a similar frequency of peptide-specific lymphocytes in the spleen but a eight-fold increase in the draining lymph-nodes. A very high frequency of CD8+ T cells, specific for the sequence PbCS 245-253, a H-2Kd-restricted CTL epitope, was obtained in the liver and spleen of mice immunized with the two regimens. Even though the frequency of H-2Kd PbCS 245-253 multimer+, CD8+ T cells was higher in gamma-spz immunized mice, the frequency of IFN-gamma producing CD8+ T cells was comparable. The phenotype of the CD8+ T cell responses was characterized with the help H-2Kd PbCS 245-253 multimer and most of the CSP-specific CD8+ T cells represented an intermediate subset between effector and central memory with CD44(high), CD45RB(high), CD62L(low) and CD122(high). The number of memory CD8+ T cells decreased after the last LSP immunization but could be boosted to higher level with live spz. The unique combination of LSP PbCS 242-310 and the adjuvant QS-21 induced an immune response that was comparable in terms of quality to the one generated with gamma-spz. This confirmed the potential of LSP as malaria vaccine candidates as well as for the study of the repertoire of targets of protective immunity in the gamma-spz vaccine model.
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Valentin
authors.initials: V
authors.lastname: Meraldi
authors.forename: Jackeline F
authors.initials: JF
authors.lastname: Romero
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kensil
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D010641:Phenotype; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D008070:Lipopolysaccharides; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; D012503:Saponins; C041595:circumsporozoite protein, Protozoan; C078785:saponin QA-21V1; D007371:Interferon-gamma