Cyclic constrained immunoreactive peptides from crucial P. falciparum proteins: potential implications in malaria diagnostics

초록

Malaria is still a global challenge with significant morbidity and mortality, especially in the African, South-East Asian, and Latin American regions. Malaria diagnosis is a crucial pillar in the control and elimination efforts, often accomplished by the administration of mass-scale Rapid diagnostic tests (RDTs). The inherent limitations of RDTs-insensitivity in scenarios of low transmission settings and deletion of one of the target proteins-Histidine rich protein 2/3 (HRP-2/3) are evident from multiple reports, thus necessitating the need to explore novel diagnostic tools/targets. The present study used peptide microarray to screen potential epitopes from 13 anti-genic proteins (CSP, EXP1, LSA1, TRAP, AARP, AMA1, GLURP, MSP1, MSP2, MSP3, MSP4, P48/45, HAP2) of P. falciparum. Three cyclic constrained immunoreactive peptides-C6 (EXP1), A8 (MSP2), B7 (GLURP) were identified from 5458 cyclic con-strained peptides (in duplicate) against P. falciparum-infected sera. Peptides (C6, A8, B7-cyclic constrained) and (G11, DSQ, NQN-corresponding linear peptides) were fairly immunoreactive towards P. falciparum-infected sera in dot-blot assay. Using direct ELISA, cyclic constrained peptides (C6 and B7) were found to be spe-cific to P. falciparum-infected sera. A substantial number of samples were tested and the peptides successfully differentiated the P. falciparum positive and negative samples with high confidence. In conclusion, the study identified 3 cyclic con-strained immunoreactive peptides (C6, B7, and A8) from P. falciparum secretory/ surface proteins and further validated for diagnostic potential of 2 peptides (C6 and B7) with field-collected P. falciparum-infected sera samples. (Translational Research 2022; 249:28-36)

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