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Peer-reviewedCC BY 4.0Nature Microbiology

Host cell traversal by Plasmodium parasites drives sterilizing T cell-mediated immunity following immunization

  • Ana Rodrigues1
  • António M. Mendes1,2
  • Rute Gonçalves1
  • Helena Nunes-Cabaço1,3
  • Sofia Marques1
  • Nuno Valente-Leal1
  • Daniel Gomes da Costa1
  • Cristina Ferreira1
  • Marc Veldhoen1,3
  • Miguel Prudêncio1,3
  • Maria M. Mota1,3
  • Ângelo Ferreira Chora1,3
  1. 1Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal
  2. 2Present Address: SGS Portugal S.A., Lisbon, Portugal
  3. 3Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
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Abstract

The development of a vaccine capable of conferring sterile protection against Plasmodium, the causative agent of malaria, is a major priority for global eradication efforts. Whole-organism vaccines using liver-infective sporozoites provide high levels of sterile protection against pre-erythrocytic infection. Yet, determinants of sporozoite immunogenicity remain poorly characterized. Here we demonstrate, using rodent models of vaccination, that the ability of Plasmodium sporozoites to actively migrate through multiple host cells before infecting hepatocytes is required for sterilizing immunity, regardless of the extent of intrahepatic development of immunizing parasites. We further establish host cell traversal as a dominant contributor to the induction of sterile protection. Impaired cell traversal precludes protective liver-resident memory CD8 T cell responses following vaccination but not the production of antiplasmodial antibodies. Our findings show that intrahepatic parasite development alone does not fully account for the magnitude and durability of protection induced by whole-sporozoite vaccination, and highlight parasite behaviour traits as critical immunogenic events shaping sterilizing cellular immunity against Plasmodium liver stages.

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Cite

BibTeXRIS
BibTeX
@article{rodrigues2026host,
  title = {{Host cell traversal by Plasmodium parasites drives sterilizing T cell-mediated immunity following immunization}},
  author = {Ana Rodrigues and António M. Mendes and Rute Gonçalves and Helena Nunes-Cabaço and Sofia Marques and Nuno Valente-Leal and Daniel Gomes da Costa and Cristina Ferreira and Marc Veldhoen and Miguel Prudêncio and Maria M. Mota and Ângelo Ferreira Chora},
  journal = {Nature Microbiology},
  year = {2026},
  month = sep,
  doi = {10.1038/s41564-026-02477-2},
  url = {https://doi.org/10.1038/s41564-026-02477-2},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Host cell traversal by Plasmodium parasites drives sterilizing T cell-mediated immunity following immunization
AU  - Ana Rodrigues
AU  - António M. Mendes
AU  - Rute Gonçalves
AU  - Helena Nunes-Cabaço
AU  - Sofia Marques
AU  - Nuno Valente-Leal
AU  - Daniel Gomes da Costa
AU  - Cristina Ferreira
AU  - Marc Veldhoen
AU  - Miguel Prudêncio
AU  - Maria M. Mota
AU  - Ângelo Ferreira Chora
PY  - 2026
DA  - 2026/09/30
JO  - Nature Microbiology
DO  - 10.1038/s41564-026-02477-2
UR  - https://doi.org/10.1038/s41564-026-02477-2
AB  - The development of a vaccine capable of conferring sterile protection against Plasmodium, the causative agent of malaria, is a major priority for global eradication efforts. Whole-organism vaccines using liver-infective sporozoites provide high levels of sterile protection against pre-erythrocytic infection. Yet, determinants of sporozoite immunogenicity remain poorly characterized. Here we demonstrate, using rodent models of vaccination, that the ability of Plasmodium sporozoites to actively migrate through multiple host cells before infecting hepatocytes is required for sterilizing immunity, regardless of the extent of intrahepatic development of immunizing parasites. We further establish host cell traversal as a dominant contributor to the induction of sterile protection. Impaired cell traversal precludes protective liver-resident memory CD8 T cell responses following vaccination but not the production of antiplasmodial antibodies. Our findings show that intrahepatic parasite development alone does not fully account for the magnitude and durability of protection induced by whole-sporozoite vaccination, and highlight parasite behaviour traits as critical immunogenic events shaping sterilizing cellular immunity against Plasmodium liver stages.
SN  - 2058-5276
ER  -