4.7 Article

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

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SCIENTIFIC REPORTS
卷 13, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-023-34903-4

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Plasmodium vivax Duffy Binding Protein region II (PvDBPII) is a leading vaccine candidate against blood-stage vivax malaria. The specific CD4(+) T cell responses to PvDBPII in natural P. vivax infection were limitedly understood. Through in vitro and in vivo experiments, six dominant T cell epitopes of PvDBPII were identified and it was found that single amino acid substitutions could alter the levels of IFN-gamma memory T cell responses. In addition, seropositivity of anti-PvDBPII antibodies were detected during acute malaria (62%) and persisted up to 12 months (11%) following P. vivax infection. Overall, these findings contribute to the development of an efficacious vivax malaria vaccine.
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-gamma and TNF-alpha cytokines. Single amino acid substitutions in three T cell epitopes altered levels of IFN-gamma 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.

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