Mass Spectrometric and Artificial Intelligence‐Based Identification of the Secretome of Plasmodium falciparum Merozoites to Provide Novel Candidates for Vaccine Development Pipeline

Author:

Munjal Akshay1,Rex Devasahayam Arokia Balaya23,Garg Prachi1,Prasad Thottethodi Subrahmanya Keshava2,Mishra Sai Kumar4,Malhotra Yuktika4,Yadav Deepika4,John Jerry4,P. Preeti4,Rawal Kamal4,Singh Shailja1ORCID

Affiliation:

1. Special Centre of Molecular Medicine Jawaharlal Nehru University New Delhi India

2. Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre Yenepoya (Deemed to be University) Mangalore India

3. Department of Laboratory Medicine and Pathology Rochester Minnesota USA

4. Center for Computational Biology and Bioinformatics Amity Institute of Biotechnology Noida Uttar Pradesh India

Abstract

ABSTRACTPurposeMerozoites are the only extracellular form of blood stage parasites, making it a worthwhile target. Multiple invasins that are stored in the merozoite apical organelles, are secreted just prior to invasion, and mediates its interaction with RBC. A comprehensive identification of all these secreted invasins is lacking and this study addresses that gap.Experimental DesignPf3D7 merozoites were enriched and triggered to discharge apical organelle contents by exposure to ionic conditions mimicking that of blood plasma. The secreted proteins were separated from cellular contents and both the fractions were subjected to proteomic analysis. Also, the identified secreted proteins were subjected to GO, PPI network analysis, and AI‐based in silico approach to understand their vaccine candidacy.ResultsA total of 63 proteins were identified in the secretory fraction with membrane and apical organellar localization. This includes various MSPs, micronemal EBAs and rhoptry bulb proteins, which play a crucial role in initial and late merozoite attachment, and majority of them qualified as vaccine candidates.Conclusion and Clinical RelevanceWe, for the first time, report the secretory repertoire of merozoite and its status for vaccine candidacy. This information can be utilized to develop better invasion blocking multisubunit vaccines, comprising of immunological epitopes from several secreted invasins.

Publisher

Wiley

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