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

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.

Automated summary

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.