Publication: Identification of conserved cross-species B-cell linear epitopes in human malaria: a subtractive proteomics and immuno-informatics approach targeting merozoite stage proteins
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2024-02-09
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Frontiers in Immunology
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Abstract
Human malaria, caused by five Plasmodium species (P. falciparum, P. vivax, P.
malariae, P. ovale, and P. knowlesi), remains a significant global health burden.
While most interventions target P. falciparum, the species associated with high
mortality rates and severe clinical symptoms, non-falciparum species exhibit
different transmission dynamics, remain hugely neglected, and pose a significant
challenge to malaria elimination efforts. Recent studies have reported the presence
of antigens associated with cross-protective immunity, which can potentially
disrupt the transmission of various Plasmodium species. With the sequencing of
the Plasmodium genome and the development of immunoinformatic tools, in this
study, we sought to exploit the evolutionary history of Plasmodium species to
identify conserved cross-species B-cell linear epitopes in merozoite proteins. We
retrieved Plasmodium proteomes associated with human malaria and applied a
subtractive proteomics approach focusing on merozoite stage proteins. Bepipred
2.0 and Epidope were used to predict B-cell linear epitopes using P. falciparum as
the reference species. The predictions were further compared against human and
non-falciparum databases and their antigenicity, toxicity, and allergenicity
assessed. Subsequently, epitope conservation was carried out using locally
sequenced P. falciparum isolates from a malaria-endemic region in western
Kenya (n=27) and Kenyan isolates from MalariaGEN version 6 (n=131). Finally,
physiochemical characteristics and tertiary structure of the B-cell linear epitopes
were determined. The analysis revealed eight epitopes that showed high similarity
(70-100%) between falciparum and non-falciparum species. These epitopes were
highly conserved when assessed across local isolates and those from the
MalariaGEN database and showed desirable physiochemical properties. Our
results show the presence of conserved cross-species B-cell linear epitopes that
could aid in targeting multiple Plasmodium species. Nevertheless, validating their
efficacy in-vitro and in-vivo experimentally is essential.