Characterization of Duffy Binding Protein II-specific CD4+T cell responses in Plasmodium vivax patients

Sci Rep. 2023 May 12;13(1):7741. doi: 10.1038/s41598-023-34903-4.

Abstract

Plasmodium vivax Duffy Binding Protein region II (PvDBPII) is a leading vaccine candidate against blood-stage vivax malaria. Anti-PvDBPII antibodies potentially block parasite invasion by inhibition of erythrocyte binding. However, knowledge of PvDBPII-specific T cell responses is limited. Here, to assess the responses of PvDBPII-specific CD4+T cells in natural P. vivax infection, three cross-sectional studies were conducted in recovered subjects. In silico analysis was used for potential T cell epitope prediction and selection. PBMCs from P. vivax subjects were stimulated with selected peptides and examined for cytokine production by ELISPOT or intracellular cytokine staining. Six dominant T cell epitopes were identified. Peptide-driven T cell responses showed effector memory CD4+T cell phenotype, secreting both IFN-γ and TNF-α cytokines. Single amino acid substitutions in three T cell epitopes altered levels of IFN-γ memory T cell responses. Seropositivity of anti-PvDBPII antibodies were detected during acute malaria (62%) and persisted up to 12 months (11%) following P. vivax infection. Further correlation analysis showed four out of eighteen subjects had positive antibody and CD4+T cell responses to PvDBPII. Altogether, PvDBPII-specific CD4+T cells were developed in natural P. vivax infections. Data on their antigenicity could facilitate development of an efficacious vivax malaria vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Carrier Proteins
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • Epitopes, T-Lymphocyte
  • Humans
  • Malaria, Vivax* / parasitology
  • Plasmodium vivax* / genetics
  • Protozoan Proteins / genetics

Substances

  • Carrier Proteins
  • Epitopes, T-Lymphocyte
  • Antigens, Protozoan
  • Protozoan Proteins
  • Cytokines
  • Antibodies, Protozoan