Cover Image

Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models

Plasmodium knowlesi utilizes the Duffy binding protein alpha (PkDBP alpha) to facilitate its invasion into human erythrocytes. PkDBP alpha region II (PkDBP alpha II) from Peninsular Malaysia and Malaysian Borneo has been shown to occur as distinct haplotypes, and the predominant haplotypes from thes...

Full description

Saved in:
Bibliographic Details
Main Authors: Azlan, Ummi Kalthum, Cheong, Fei Wen, Lau, Yee Ling, Fong, Mun Yik
Format: Article
Published: Springer Verlag (Germany) 2022
Subjects:
R Medicine
Online Access:http://eprints.um.edu.my/40885/
Tags: Add Tag
No Tags, Be the first to tag this record!
id my.um.eprints.40885
record_format eprints
spelling my.um.eprints.408852023-09-25T07:40:20Z http://eprints.um.edu.my/40885/ Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models Azlan, Ummi Kalthum Cheong, Fei Wen Lau, Yee Ling Fong, Mun Yik R Medicine Plasmodium knowlesi utilizes the Duffy binding protein alpha (PkDBP alpha) to facilitate its invasion into human erythrocytes. PkDBP alpha region II (PkDBP alpha II) from Peninsular Malaysia and Malaysian Borneo has been shown to occur as distinct haplotypes, and the predominant haplotypes from these geographical areas demonstrated differences in binding activity to human erythrocytes in erythrocyte binding assays. This study aimed to determine the effects of genetic polymorphisms in PkDBP alpha II to immune responses in animal models. The recombinant PkDBP alpha II (similar to 45 kDa) of Peninsular Malaysia (PkDBP alpha II-H) and Malaysian Borneo (PkDBP alpha II-S) were expressed in a bacterial expression system, purified, and used in mice and rabbit immunization. The profile of cytokines IL-1ra, IL-2, IL-6, IL-10, TNF-alpha, and IFN-gamma in immunized mice spleen was determined via ELISA. The titer and IgG subtype distribution of raised antibodies was characterized. Immunized rabbit sera were purified and used to perform an in vitro merozoite invasion inhibition assay. The PkDBP alpha II-immunized mice sera of both groups showed high antibody titer and a similar IgG subtype distribution pattern: IgG2b > IgG1 > IgG2a > IgG3. The PkDBP alpha II-H group was shown to have higher IL-1ra (P = 0.141) and IL-6 (P = 0.049) concentrations, with IL-6 levels significantly higher than that of the PkDBP alpha II-S group (P <= 0.05). Merozoite invasion inhibition assay using purified anti-PkDBP alpha II antibodies showed a significantly higher inhibition rate in the PkDBP alpha II-H group than the PkDBP alpha II-S group (P <= 0.05). Besides, anti-PkDBP alpha II-H antibodies were able to exhibit inhibition activity at a lower concentration than anti-PkDBP alpha II-S antibodies. PkDBP alpha II was shown to be immunogenic, and the PkDBP alpha II haplotype from Peninsular Malaysia exhibited higher responses in cytokines IL-1ra and IL-6, antibody IgM level, and merozoite invasion inhibition assay than the Malaysian Borneo haplotype. This suggests that polymorphisms in the PkDBP alpha II affect the level of immune responses in the host. Springer Verlag (Germany) 2022-12 Article PeerReviewed Azlan, Ummi Kalthum and Cheong, Fei Wen and Lau, Yee Ling and Fong, Mun Yik (2022) Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models. Parasitology Research, 121 (12). pp. 3443-3454. ISSN 0932-0113, DOI https://doi.org/10.1007/s00436-022-07665-7 <https://doi.org/10.1007/s00436-022-07665-7>. 10.1007/s00436-022-07665-7
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Azlan, Ummi Kalthum
Cheong, Fei Wen
Lau, Yee Ling
Fong, Mun Yik
Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models
description Plasmodium knowlesi utilizes the Duffy binding protein alpha (PkDBP alpha) to facilitate its invasion into human erythrocytes. PkDBP alpha region II (PkDBP alpha II) from Peninsular Malaysia and Malaysian Borneo has been shown to occur as distinct haplotypes, and the predominant haplotypes from these geographical areas demonstrated differences in binding activity to human erythrocytes in erythrocyte binding assays. This study aimed to determine the effects of genetic polymorphisms in PkDBP alpha II to immune responses in animal models. The recombinant PkDBP alpha II (similar to 45 kDa) of Peninsular Malaysia (PkDBP alpha II-H) and Malaysian Borneo (PkDBP alpha II-S) were expressed in a bacterial expression system, purified, and used in mice and rabbit immunization. The profile of cytokines IL-1ra, IL-2, IL-6, IL-10, TNF-alpha, and IFN-gamma in immunized mice spleen was determined via ELISA. The titer and IgG subtype distribution of raised antibodies was characterized. Immunized rabbit sera were purified and used to perform an in vitro merozoite invasion inhibition assay. The PkDBP alpha II-immunized mice sera of both groups showed high antibody titer and a similar IgG subtype distribution pattern: IgG2b > IgG1 > IgG2a > IgG3. The PkDBP alpha II-H group was shown to have higher IL-1ra (P = 0.141) and IL-6 (P = 0.049) concentrations, with IL-6 levels significantly higher than that of the PkDBP alpha II-S group (P <= 0.05). Merozoite invasion inhibition assay using purified anti-PkDBP alpha II antibodies showed a significantly higher inhibition rate in the PkDBP alpha II-H group than the PkDBP alpha II-S group (P <= 0.05). Besides, anti-PkDBP alpha II-H antibodies were able to exhibit inhibition activity at a lower concentration than anti-PkDBP alpha II-S antibodies. PkDBP alpha II was shown to be immunogenic, and the PkDBP alpha II haplotype from Peninsular Malaysia exhibited higher responses in cytokines IL-1ra and IL-6, antibody IgM level, and merozoite invasion inhibition assay than the Malaysian Borneo haplotype. This suggests that polymorphisms in the PkDBP alpha II affect the level of immune responses in the host.
format Article
author Azlan, Ummi Kalthum
Cheong, Fei Wen
Lau, Yee Ling
Fong, Mun Yik
author_facet Azlan, Ummi Kalthum
Cheong, Fei Wen
Lau, Yee Ling
Fong, Mun Yik
author_sort Azlan, Ummi Kalthum
title Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models
title_short Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models
title_full Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models
title_fullStr Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models
title_full_unstemmed Plasmodium knowlesi Duffy binding protein alpha region II (PkDBP alpha II) in clinical isolates from Peninsular Malaysia and Malaysian Borneo exhibit different immune responses in animal models
title_sort plasmodium knowlesi duffy binding protein alpha region ii (pkdbp alpha ii) in clinical isolates from peninsular malaysia and malaysian borneo exhibit different immune responses in animal models
publisher Springer Verlag (Germany)
publishDate 2022
url http://eprints.um.edu.my/40885/
_version_ 1778161623372922880
score 13.211869

Similar Items