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Peer-reviewedCC BY-NCScience Advances

Accessing invasion-competent Plasmodium vivax merozoites reveals antibody-dependent NK cell activation

  • Jeremy Salvador1
  • Lucas Guselli1
  • Romminea Yeat1
  • Sokchea Lay2
  • Titsophantharoth Thol1
  • Nisa Ya2
  • Lionel Brice Feufack-Donfack1
  • Sievleang Heng2
  • Candice Bohaud2
  • Agnes Orban1
  • Léa Baldor1
  • Baura Tat1
3 more authors
  • Chetan E. Chitnis3
  • Tineke Cantaert2,4
  • Jean Popovici1,5
5 affiliations
  1. 1Malaria Research Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
  2. 2Immunology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
  3. 3Malaria Parasite Biology and Vaccines Unit, INSERM UMR 1347 ParasitInnov, Université Paris Cité, Institut Pasteur, Paris, France.
  4. 4Ecology and Emergence of Arthropod-borne Diseases, Institut Pasteur, Paris, France.
  5. 5Infectious Disease Epidemiology and Analytics, Institut Pasteur, Paris, France.
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Abstract

Malaria pathogenesis and clinical symptoms arise from blood-stage replication of Plasmodium parasites, which depends on rapid invasion of red blood cells by merozoites. Despite the central importance of this stage, direct functional studies of Plasmodium vivax (P. vivax) merozoites remain limited by the lack of continuous in vitro culture and restricted access to 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 enabling synchronized release and high-yield isolation of invasion-competent P. vivax merozoites from ex vivo cultures. Reversible inhibition of parasite egress using the PKG inhibitor ML10 enables synchronization at the segmented schizont stage, followed by rapid mechanical release 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 demonstrate that antibody-opsonized P. vivax merozoites activate human natural killer cells, revealing functional antibody-dependent immune responses.

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Cite

BibTeXRIS
BibTeX
@article{salvador2026accessing,
  title = {{Accessing invasion-competent Plasmodium vivax merozoites reveals antibody-dependent NK cell activation}},
  author = {Jeremy Salvador and Lucas Guselli and Romminea Yeat and Sokchea Lay and Titsophantharoth Thol and Nisa Ya and Lionel Brice Feufack-Donfack and Sievleang Heng and Candice Bohaud and Agnes Orban and Léa Baldor and Baura Tat and Chetan E. Chitnis and Tineke Cantaert and Jean Popovici},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh3417},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh3417},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Accessing invasion-competent Plasmodium vivax merozoites reveals antibody-dependent NK cell activation
AU  - Jeremy Salvador
AU  - Lucas Guselli
AU  - Romminea Yeat
AU  - Sokchea Lay
AU  - Titsophantharoth Thol
AU  - Nisa Ya
AU  - Lionel Brice Feufack-Donfack
AU  - Sievleang Heng
AU  - Candice Bohaud
AU  - Agnes Orban
AU  - Léa Baldor
AU  - Baura Tat
AU  - Chetan E. Chitnis
AU  - Tineke Cantaert
AU  - Jean Popovici
PY  - 2026
DA  - 2026/10/21
JO  - Science Advances
DO  - 10.1126/sciadv.aeh3417
UR  - https://www.science.org/doi/10.1126/sciadv.aeh3417
AB  - Malaria pathogenesis and clinical symptoms arise from blood-stage replication of Plasmodium parasites, which depends on rapid invasion of red blood cells by merozoites. Despite the central importance of this stage, direct functional studies of Plasmodium vivax (P. vivax) merozoites remain limited by the lack of continuous in vitro culture and restricted access to 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 enabling synchronized release and high-yield isolation of invasion-competent P. vivax merozoites from ex vivo cultures. Reversible inhibition of parasite egress using the PKG inhibitor ML10 enables synchronization at the segmented schizont stage, followed by rapid mechanical release 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 demonstrate that antibody-opsonized P. vivax merozoites activate human natural killer cells, revealing functional antibody-dependent immune responses.
SN  - 2375-2548
ER  -