Accessing invasion-competent Plasmodium vivax merozoites reveals antibody-dependent NK cell activation
Year: 2026
Type: article
Abstract: Malaria pathogenesis and clinical symptoms arise from blood-stage replication of Plasmodium parasites, which depends on rapid invasion of red blood cell by merozoites. Despite the central importance of this stage, direct functional studies of Plasmodium vivax merozoites have been severely limited by the lack of continuous in vitro culture and the inability to routinely access viable, invasion-competent merozoites from clinical isolates. Consequently, key aspects of P. vivax merozoite biology and immune recognition remain poorly defined. Here, we establish a robust platform that enables synchronized release and high-yield isolation of invasion-competent P. vivax merozoites directly from ex vivo cultures. Reversible inhibition of parasite egress using the cGMP-dependent protein kinase inhibitor ML10 allows precise synchronization at the segmented schizont stage, followed by rapid mechanical liberation of merozoites using a liposome-based extrusion approach. This workflow yields highly pure merozoites with recovery rates exceeding 75% while preserving structural integrity and invasive capacity. Leveraging this platform, we provide direct functional evidence that antibody opsonized P. vivax merozoites activate human natural killer cells consistent with antibody-dependent cellular cytotoxicity mechanisms. Together, this study overcomes a long-standing technical barrier and enables direct investigation of P. vivax merozoite invasion biology and immune effector responses.
Source: Science Advances
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G3524766724, Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa, G5777116358, Characterisation of the immunological mechanisms that drive chronic chikungunya disease pathogenesis, Mechanisms of Antibody-Dependent Enhancement of Dengue Disease, Extent, dynamics and mechanisms of Plasmodium vivax immune evasion caused by PvDBP gene amplification, Comprehensive characterization of the genetic factors and the host immune response associated to protection from clinical Plasmodium vivax malaria, Leveraging access to parasite natural diversity to identify Plasmodium vivax culture-adaptable strain.
OpenAlex ID: W7223099752