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Plasmodium vivax spleen-dependent genes encode antigens associated with cytoadhesion and clinical protection.
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The most widely distributed human malaria parasite, causes severe
clinical syndromes despite low peripheral blood parasitemia.
This conundrum is further complicated as cytoadherence in the
microvasculature is still a matter of investigations. Previous
reports in " - ", another parasite species shown to infect
humans, demonstrated that variant genes involved in
cytoadherence were dependent on the spleen for their expression.
Hence, using a global transcriptional analysis of parasites
obtained from spleen-intact and splenectomized monkeys, we
identified 67 " - " genes whose expression was spleen dependent.
To determine their role in cytoadherence, two " - " transgenic
lines expressing two variant proteins pertaining to VIR and
Pv-FAM-D multigene families were used. Cytoadherence assays
demonstrated specific binding to human spleen but not lung
fibroblasts of the transgenic line expressing the VIR14 protein.
To gain more insights, we expressed five " - " spleen-dependent
genes as recombinant proteins, including members of three
different multigene families (VIR, Pv-FAM-A, Pv-FAM-D), one
membrane transporter (SECY), and one hypothetical protein
(HYP1), and determined their immunogenicity and association with
clinical protection in a prospective study of 383 children in
Papua New Guinea. Results demonstrated that spleen-dependent
antigens are immunogenic in natural infections and that
antibodies to HYP1 are associated with clinical protection.
These results suggest that the spleen plays a major role in
expression of parasite proteins involved in cytoadherence and can reveal antigens associated with clinical protection, thus
prompting a paradigm shift in " - " biology toward deeper
studies of the spleen during infections
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FERNÁNDEZ BECERRA, Carmen, et al. Plasmodium vivax spleen-dependent genes encode antigens associated with cytoadhesion and clinical protection. Proceedings of the National Academy of Sciences of the United States of America. 2020. Vol. vol 117, num. num 23. ISSN 0027-8424. [consulted: 14 of October of 2026]. Available at: https://hdl.handle.net/2445/182978