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 (γ-spz) and is mediated by IFN-γ 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 γ-spz. The ex vivo evaluation of the CD8 + T cell response by IFN-γ ELISPOT assay revealed that the injection of LSP with QS-21 induced, compared to γ-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-2K d-restricted CTL epitope, was obtained in the liver and spleen of mice immunized with the two regimens. Even though the frequency of H-2K d PbCS 245–253 multimer +, CD8 + T cells was higher in γ-spz immunized mice, the frequency of IFN-γ producing CD8 + T cells was comparable. The phenotype of the CD8 + T cell responses was characterized with the help H-2K d 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 γ-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 γ-spz vaccine model.