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

Kapil Vashisht, View ORCID ProfileSukrit Srivastava, Vandana, Ram Das, Supriya Sharma, Nitin Bhardwaj, Anupkumar R Anvikar, Tong-Soo Kim, Byoung-Kuk Na, Ho-Joon Shin, Kailash C Pandey
doi: https://doi.org/10.1101/2021.10.11.463910
Kapil Vashisht
1ICMR-National Institute of Malaria Research, Delhi, India
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Sukrit Srivastava
2Indian Foundation for Fundamental Research, Uttar Pradesh, India
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  • ORCID record for Sukrit Srivastava
Vandana
1ICMR-National Institute of Malaria Research, Delhi, India
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Ram Das
1ICMR-National Institute of Malaria Research, Delhi, India
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Supriya Sharma
1ICMR-National Institute of Malaria Research, Delhi, India
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Nitin Bhardwaj
1ICMR-National Institute of Malaria Research, Delhi, India
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Anupkumar R Anvikar
1ICMR-National Institute of Malaria Research, Delhi, India
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Tong-Soo Kim
3Inha University, Incheon, South Korea
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Byoung-Kuk Na
4Gyeongsang University, Jinju, South Korea
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Ho-Joon Shin
5Ajou University, Suwon, South Korea
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Kailash C Pandey
1ICMR-National Institute of Malaria Research, Delhi, India
6Academy of Scientific and Innovative Research (AcSIR), Uttar Pardesh, India
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  • For correspondence: kailash.pandey@icmr.gov.in
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Abstract

Malaria is still a global challenge with significant morbidity and mortality, especially in the African, South-East Asian and Latin American region. Malaria diagnosis is a crucial pillar in the control and elimination efforts, often accomplished by administration of mass-scale Rapid diagnostic tests (RDTs). The inherent limitations of RDTs-failure of detection in low transmission settings, and deletion of one of the target proteins-Histidine rich protein (HRP) 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 antigenic 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 5,458 cyclic constrained 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 indirect ELISA, cyclic constrained peptides (C6 & B7) were found to be specific to P. falciparum infected sera and further, observed to be significantly reactive towards antibodies from field-collected P. falciparum infected sera. Notably, the structural location of the epitopes defines the reactivity, observed by the preferential recognition of cyclic constrained peptides vs linear peptides and corroborated by the homology modeling analysis of selected proteins. In conclusion, the study identified three cyclic constrained immunoreactive peptides (C6, B7 & A8) from P. falciparum secretory/surface proteins and two of them (C6 & B7) were validated for their diagnostic potential with field-collected P. falciparum infected sera samples.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 11, 2021.
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Cyclic constrained immunoreactive peptides from crucial P. falciparum proteins: potential implications in malaria diagnostics
Kapil Vashisht, Sukrit Srivastava, Vandana, Ram Das, Supriya Sharma, Nitin Bhardwaj, Anupkumar R Anvikar, Tong-Soo Kim, Byoung-Kuk Na, Ho-Joon Shin, Kailash C Pandey
bioRxiv 2021.10.11.463910; doi: https://doi.org/10.1101/2021.10.11.463910
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Cyclic constrained immunoreactive peptides from crucial P. falciparum proteins: potential implications in malaria diagnostics
Kapil Vashisht, Sukrit Srivastava, Vandana, Ram Das, Supriya Sharma, Nitin Bhardwaj, Anupkumar R Anvikar, Tong-Soo Kim, Byoung-Kuk Na, Ho-Joon Shin, Kailash C Pandey
bioRxiv 2021.10.11.463910; doi: https://doi.org/10.1101/2021.10.11.463910

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