Mass spectrometric identification of the secretome of Plasmodium
falciparum merozoites to provide novel candidates for vaccine
development pipeline
Abstract
Purpose: Merozoites are the only extracellular form of blood stage
parasites, making it a worthwhile target for vaccine and drug
development. Multiple invasins that are stored in the merozoite apical
organelles, are secreted just prior to invasion, and mediates its
interaction with host cell. A comprehensive identification of all these
secreted invasins is lacking and this study addresses that gap.
Experimental design: Pf3D7 merozoites were enriched and were 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 gene ontology and PPI network analysis. Results: A total of
63 proteins were identified in the secretory fraction with membrane and
apical organellar localization. This includes various MSPs, micronemal
EBAs, various rhoptry bulb proteins, which plays a crucial role in
initial and late attachment of the merozoite with the RBC, and harboured
multiple linear B cell epitopes. Conclusion and clinical relevance: We,
for the first time, report the secretory repertoire of merozoite. This
information can be utilized to develop better invasion blocking
multisubunit vaccines, comprising of immunological epitopes from several
secreted invasins.