Functional and immunological mapping of domains of the reticulocyte binding protein, Plasmodium vivax PvRBP2a

Matthew Zirui Tay; Weiyi Tang; Wenn-Chyau Lee; Alice Soh Meoy Ong; Wisna Novera; Benoît Malleret; Guillaume Carissimo; Ann-Marie Chacko; Abbas El-Sahili; Julien Lescar; Yiping Fan; Rose M McGready; Cindy S Chu; Jerry Kok Yen Chan; Lisa F P Ng; Bruce Russell; François Nosten; Laurent Rénia

doi:10.1093/infdis/jiae111

Functional and immunological mapping of domains of the reticulocyte binding protein, Plasmodium vivax PvRBP2a

J Infect Dis. 2024 Mar 5:jiae111. doi: 10.1093/infdis/jiae111. Online ahead of print.

Authors

Matthew Zirui Tay¹, Weiyi Tang¹, Wenn-Chyau Lee^{1

2}, Alice Soh Meoy Ong¹, Wisna Novera³, Benoît Malleret⁴, Guillaume Carissimo^{1

5}, Ann-Marie Chacko³, Abbas El-Sahili⁶, Julien Lescar⁶, Yiping Fan^{7

8

9}, Rose M McGready^{10

11}, Cindy S Chu^{10

11}, Jerry Kok Yen Chan^{7

8

9}, Lisa F P Ng^{1

12

13}, Bruce Russell¹⁴, François Nosten^{10

11}, Laurent Rénia^{1

13}

Affiliations

¹ A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #05-13, Singapore 138648, Singapore.
² Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
³ Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore.
⁴ Department of Microbiology and Immunology, Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
⁵ Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
⁶ NTU Institute for Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, Singapore 636921, Singapore.
⁷ Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.
⁸ Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
⁹ Academic Clinical Program in Obstetrics and Gynaecology, Duke-NUS Medical School, Singapore 168753, Singapore.
¹⁰ Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
¹¹ Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Old Road, Oxford OX3 7LJ, UK.
¹² Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
¹³ Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.
¹⁴ Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.

PMID: 38441336
DOI: 10.1093/infdis/jiae111

Abstract

We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. We assessed the PvRBP2a epitopes involved in CD98 binding and recognised by antibodies from infected patients using linear epitope mapping. We identified two epitope clusters mediating PvRBP2a-CD98 interaction. One cluster named cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in P. vivax-infected humans. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood stage vaccine against P. vivax.

Keywords: Plasmodium vivax; CD98; PVRBP2a; invasion; reticulocytes.