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Sci Rep. 2019 Mar 7;9(1):3906. doi: 10.1038/s41598-019-40321-2.

Inhibition of parasite invasion by monoclonal antibody against epidermal growth factor-like domain of Plasmodium vivax merozoite surface protein 1 paralog.

Author information

1
Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
2
Department of Microbiology and Immunology, University of Otago, Dunedin, 9054, New Zealand.
3
Department of Public Health and Preventive Medicine, Laboratory of Pathogen Infection and Immunity, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, People's Republic of China.
4
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 117597, Singapore; Singapore Immunology Network (SIgN), A*STAR, Singapore, 138648, Singapore.
5
Jenner Institute Laboratories, Old Road Campus Research Building, University of Oxford, Oxford, United Kingdom.
6
Department of Medical Research, Yangon, Myanmar.
7
Department of Cellular and Molecular Biology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
8
Department of Obstetrics and Gynecology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
9
Department of Physiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
10
Department of Internal Medicine, School of Medicine, Kangwon national University, Chuncheon, Gangwon-do, Republic of Korea.
11
Department of Microbiology, Ajou University School of Medicine, and Department of Biomedical Science, Ajou University Graduate School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
12
Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea. etaekhan@gmail.com.

Abstract

The Plasmodium vivax merozoite surface protein 1 paralog (PvMSP1P), which has epidermal growth factor (EGF)-like domains, was identified as a novel erythrocyte adhesive molecule. This EGF-like domain (PvMSP1P-19) elicited high level of acquired immune response in patients. Antibodies against PvMSP1P significantly reduced erythrocyte adhesion activity to its unknown receptor. To determine PvMSP1P-19-specific antibody function and B-cell epitopes in vivax patients, five monoclonal antibodies (mAbs) and 18-mer peptides were generated. The mAb functions were determined by erythrocyte-binding inhibition assay and invasion inhibition assay with P. knowlesi. B-cell epitopes of PvMSP1P-19 domains were evaluated by peptide microarray. The pvmsp1p-19 sequences showed limited polymorphism in P. vivax worldwide isolates. The 1BH9-A10 showed erythrocyte binding inhibitory by interaction with the N-terminus of PvMSP1P-19, while this mAb failed to recognize PkMSP1P-19 suggesting the species-specific for P. vivax. Other mAbs showed cross-reactivity with PkMSP1P-19. Among them, the 2AF4-A2 and 2AF4-A6 mAb significantly reduced parasite invasion through C-terminal recognition. The linear B-cell epitope in naturally exposed P. vivax patient was identified at three linear epitopes. In this study, PvMSP1P-19 N-terminal-specific 1BH9-A10 and C-terminal-specific 2AF4 mAbs showed functional activity for epitope recognition suggesting that PvMSP1P may be useful for vaccine development strategy for specific single epitope to prevent P. vivax invasion.

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