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Peer-reviewedCC BYJournal of Infection

Protective immunity to clinical malaria is modified by the genetic diversity of

  • Myo T. Naung
  • Ramin Mazhari1
  • Rhea J. Longley2
  • Somya Mehra3
  • Wilson Wong4
  • Paolo Bareng5
  • Moses Laman6
  • Benson Kiniboro6
  • Maria Ome-Kaius6
  • Pascal Michon7
  • James Beeson8
  • Eizo Takashima9
6 more authors
  • Hikaru Nagaoka9
  • Shannon Takala-Harrison10
  • Takafumi Tsuboi11
  • Leanne J. Robinson12
  • Ivo Mueller13
  • Alyssa E. Barry
13 affiliations
  1. 1Infection and Global Health Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  2. 2Infection and Global Health Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
  3. 3Infection and Global Health Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Disease Elimination and Maternal and Child Health, Burnet Institute, Melbourne, Victoria, Australia
  4. 4Infection and Global Health Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
  5. 5Centre for Innovation in Infectious Diseases and Immunology Research (CIIDIR), Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, Geelong, Victoria, Australia; Disease Elimination and Maternal and Child Health, Burnet Institute, Melbourne, Victoria, Australia
  6. 6Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea
  7. 7National University of Vanuatu, Avenue Léopold Sédar Senghor, Port-Vila, Vanuatu
  8. 8Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia; Disease Elimination and Maternal and Child Health, Burnet Institute, Melbourne, Victoria, Australia
  9. 9Division of Malaria Research, Proteo-Science Center, Ehime University, Japan
  10. 10Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States
  11. 11Division of Cell-Free Sciences, Proteo-Science Center, Ehime University, Japan
  12. 12Infection and Global Health Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Disease Elimination and Maternal and Child Health, Burnet Institute, Melbourne, Victoria, Australia
  13. 13Infection and Global Health Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Department of Parasites and Insect Vectors, Pasteur Institute, Paris, France
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Abstract

Prioritising malaria vaccine targets requires understanding immunity to genetically and structurally diverse parasite antigens, influencing antibody measurements and durability. We measured total IgG levels to 25 Plasmodium falciparum antigens and assessed their association with protection and antigen features. Antibodies were quantified in two longitudinal cohorts of Papua New Guinean children (5–14 years; n=647) experiencing high or moderate transmission. Associations between antibody levels and time to first clinical malaria episode were evaluated using Cox regression and Bayesian antibody-kinetics models, incorporating antigen genetic diversity and structural properties. In high-transmission settings, antibody levels were elevated and stable, with the strongest protection observed for conserved, low-diversity antigens dominated by the 3D7-reference-matching haplotypes and enriched for intrinsically disordered and alpha-helical regions. In moderate transmission, antibody levels were variable, decayed over time, and reflected recent exposure. These findings identify antigen diversity as a key modifier of malaria immunity and underscore the importance of antigen features.

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Cite

BibTeXRIS
BibTeX
@article{naung2026protective,
  title = {{Protective immunity to clinical malaria is modified by the genetic diversity of}},
  author = {Myo T. Naung and Ramin Mazhari and Rhea J. Longley and Somya Mehra and Wilson Wong and Paolo Bareng and Moses Laman and Benson Kiniboro and Maria Ome-Kaius and Pascal Michon and James Beeson and Eizo Takashima and Hikaru Nagaoka and Shannon Takala-Harrison and Takafumi Tsuboi and Leanne J. Robinson and Ivo Mueller and Alyssa E. Barry},
  journal = {Journal of Infection},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jinf.2026.106845},
  url = {https://doi.org/10.1016/j.jinf.2026.106845},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Protective immunity to clinical malaria is modified by the genetic diversity of
AU  - Myo T. Naung
AU  - Ramin Mazhari
AU  - Rhea J. Longley
AU  - Somya Mehra
AU  - Wilson Wong
AU  - Paolo Bareng
AU  - Moses Laman
AU  - Benson Kiniboro
AU  - Maria Ome-Kaius
AU  - Pascal Michon
AU  - James Beeson
AU  - Eizo Takashima
AU  - Hikaru Nagaoka
AU  - Shannon Takala-Harrison
AU  - Takafumi Tsuboi
AU  - Leanne J. Robinson
AU  - Ivo Mueller
AU  - Alyssa E. Barry
PY  - 2026
DA  - 2026/10/23
JO  - Journal of Infection
DO  - 10.1016/j.jinf.2026.106845
UR  - https://doi.org/10.1016/j.jinf.2026.106845
AB  - Prioritising malaria vaccine targets requires understanding immunity to genetically and structurally diverse parasite antigens, influencing antibody measurements and durability. We measured total IgG levels to 25 Plasmodium falciparum antigens and assessed their association with protection and antigen features. Antibodies were quantified in two longitudinal cohorts of Papua New Guinean children (5–14 years; n=647) experiencing high or moderate transmission. Associations between antibody levels and time to first clinical malaria episode were evaluated using Cox regression and Bayesian antibody-kinetics models, incorporating antigen genetic diversity and structural properties. In high-transmission settings, antibody levels were elevated and stable, with the strongest protection observed for conserved, low-diversity antigens dominated by the 3D7-reference-matching haplotypes and enriched for intrinsically disordered and alpha-helical regions. In moderate transmission, antibody levels were variable, decayed over time, and reflected recent exposure. These findings identify antigen diversity as a key modifier of malaria immunity and underscore the importance of antigen features.
SN  - 1532-2742
ER  -