%0 Journal Article
%A van Dijk, Hannah
%A Wahl, Ilka
%A Kraker, Sara
%A Robben, Paul M
%A Dutta, Sheetij
%A Wardemann, Hedda
%T Epitope and HLA specificity of human TCRs against Plasmodium falciparum circumsporozoite protein.
%J Journal of experimental medicine
%V 222
%N 9
%@ 0022-1007
%C New York, NY
%I Rockefeller Univ. Press
%M DKFZ-2025-01427
%P e20250044
%D 2025
%Z #EA:D130#LA:D130#
%X Plasmodium falciparum malaria remains a significant global health challenge. Current vaccines elicit antibody responses against circumsporozoite protein (PfCSP) that prevent the infection of hepatocytes but offer only moderate protection. Cellular immunity has emerged as a critical component of preerythrocytic protection that might be leveraged to develop improved PfCSP vaccines. Here, we characterized the clonality, molecular features, epitope specificity, and HLA restrictions of the human PfCSP-specific CD4+ and CD8+ T cell response to vaccination with an adjuvanted PfCSP vaccine, FMP013/ALFQ. Using TCR expression cloning, we identified novel conserved CD4+ T cell epitopes in the PfCSP N terminus and showed that the C-terminal CS.T3 epitope was targeted by CD4+ and rare CD8+ T cells, which recognized this epitope co-receptor independently presented on a class II HLA. Our findings provide insights into the utility of these epitopes as targets for strain-transcending immunity compared with the immunodominant but highly polymorphic epitopes in the PfCSP C terminus, offering guidance for the design of improved malaria vaccines.
%K Humans
%K Plasmodium falciparum: immunology
%K Protozoan Proteins: immunology
%K Epitopes, T-Lymphocyte: immunology
%K Malaria Vaccines: immunology
%K CD4-Positive T-Lymphocytes: immunology
%K Malaria, Falciparum: immunology
%K Malaria, Falciparum: prevention & control
%K Receptors, Antigen, T-Cell: immunology
%K Receptors, Antigen, T-Cell: genetics
%K CD8-Positive T-Lymphocytes: immunology
%K HLA Antigens: immunology
%K Amino Acid Sequence
%K Protozoan Proteins (NLM Chemicals)
%K circumsporozoite protein, Protozoan (NLM Chemicals)
%K Epitopes, T-Lymphocyte (NLM Chemicals)
%K Malaria Vaccines (NLM Chemicals)
%K Receptors, Antigen, T-Cell (NLM Chemicals)
%K HLA Antigens (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40637713
%2 pmc:PMC12243953
%R 10.1084/jem.20250044
%U https://inrepo02.dkfz.de/record/302887