The study was done in a subset of children enrolled in five randomised controlled trials in Navrongo, Ghana; Kilimanjaro, Tanzania; Manhica, Mozambique; Kisumu, Kenya; and Bungoma, Kenya.
RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum, is undergoing clinical trials.
Our studies demonstrate that skin exoerythrocytic stages are susceptible to destruction in immunized mice, suggesting that their aberrant location does not protect them from the host's adaptive immune response.
We demonstrate that immunization with p52-GAP sporozoites also results in a strong increase of effector memory CD8+ T cells, even 6 months after immunization, whereas no specific CD4+ effector T cells response could be detected. In addition, we show that the increase of effector memory CD8+ T cells is specific for the liver and not for the spleen or lymph nodes.
We conclude that processing of the CS protein derived from the RTS,S antigen leads to the generation of HLA-DR-restricted epitopes that are similar to those identified previously using CD4 T cells from subjects immunized with and protected by attenuated sporozoites or exposed to infectious sporozoites.
The panel of MSP4-specific Mabs produced were found to recognize six distinct epitopes that are also targeted by human antibodies during natural malaria infection.
We show here that when it is administered as a recombinant protein (P) in Montanide ISA720 adjuvant, followed by a recombinant human type 5 adenovirus (Ad), intense and long-lasting Plasmodium vivax AMA-1-specific antibody responses (including both IgG1 and IgG2a), as well as proliferative memory T cell responses, can be detected in immunized mice.
These results give further support to the need for preclinical studies of P. vivax vaccine candidate AMA-1 administered in prime/boost protocols that include recombinant proteins and adenoviral vectors.
Sterile protection against infection with Plasmodium sporozoites requires high numbers of memory CD8 T cells.
These findings may have implications for the current understanding of the natural acquisition of clinical immunity to malaria as well as for rational vaccine design.