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Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China
BACKGROUND: Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is li...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611641/ https://www.ncbi.nlm.nih.gov/pubmed/34819151 http://dx.doi.org/10.1186/s13071-021-05086-6 |
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author | Xu, Qinwen Liu, Sihong Kassegne, Kokouvi Yang, Bo Lu, Jiachen Sun, Yifan Zhong, Wenli Zhang, Miaosa Liu, Yaobao Zhu, Guoding Cao, Jun Cheng, Yang |
author_facet | Xu, Qinwen Liu, Sihong Kassegne, Kokouvi Yang, Bo Lu, Jiachen Sun, Yifan Zhong, Wenli Zhang, Miaosa Liu, Yaobao Zhu, Guoding Cao, Jun Cheng, Yang |
author_sort | Xu, Qinwen |
collection | PubMed |
description | BACKGROUND: Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP1(19)). This study aims to analyze the genetic diversity and immunogenicity of PoMSP1(19). METHODS: A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp1(19) (pocmsp1(19)) and P. ovale wallikeri (pow) msp1(19) (powmsp1(19)) genes by polymerase chain reaction. The genetic diversity of pomsp1(19) was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP1(19) (rPoMSP1(19))-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP1(19)-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays. RESULTS: Sequences of pomsp1(19) were found to be thoroughly conserved in all the clinical isolates. rPoMSP1(19) proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP1(19)-GST were observed. rPoMSP1(19)-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP1(19) and rPowMSP1(19), respectively. Cross-reactivity between rPocMSP1(19) and rPowMSP1(19) was observed. Cellular immune responses to rPocMSP1(19) (69.51%) and rPowMSP1(19) (52.17%) induced in rPocMSP1(19)- and rPowMSP1(19)-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP1(19)-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively. CONCLUSIONS: This study revealed highly conserved gene sequences of pomsp1(19). In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP1(19) in mice was also identified. These instructive findings should encourage further testing of PoMSP1(19) for rational vaccine design. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-021-05086-6. |
format | Online Article Text |
id | pubmed-8611641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86116412021-11-24 Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China Xu, Qinwen Liu, Sihong Kassegne, Kokouvi Yang, Bo Lu, Jiachen Sun, Yifan Zhong, Wenli Zhang, Miaosa Liu, Yaobao Zhu, Guoding Cao, Jun Cheng, Yang Parasit Vectors Research BACKGROUND: Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP1(19)). This study aims to analyze the genetic diversity and immunogenicity of PoMSP1(19). METHODS: A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp1(19) (pocmsp1(19)) and P. ovale wallikeri (pow) msp1(19) (powmsp1(19)) genes by polymerase chain reaction. The genetic diversity of pomsp1(19) was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP1(19) (rPoMSP1(19))-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP1(19)-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays. RESULTS: Sequences of pomsp1(19) were found to be thoroughly conserved in all the clinical isolates. rPoMSP1(19) proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP1(19)-GST were observed. rPoMSP1(19)-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP1(19) and rPowMSP1(19), respectively. Cross-reactivity between rPocMSP1(19) and rPowMSP1(19) was observed. Cellular immune responses to rPocMSP1(19) (69.51%) and rPowMSP1(19) (52.17%) induced in rPocMSP1(19)- and rPowMSP1(19)-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP1(19)-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively. CONCLUSIONS: This study revealed highly conserved gene sequences of pomsp1(19). In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP1(19) in mice was also identified. These instructive findings should encourage further testing of PoMSP1(19) for rational vaccine design. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-021-05086-6. BioMed Central 2021-11-24 /pmc/articles/PMC8611641/ /pubmed/34819151 http://dx.doi.org/10.1186/s13071-021-05086-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xu, Qinwen Liu, Sihong Kassegne, Kokouvi Yang, Bo Lu, Jiachen Sun, Yifan Zhong, Wenli Zhang, Miaosa Liu, Yaobao Zhu, Guoding Cao, Jun Cheng, Yang Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China |
title | Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China |
title_full | Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China |
title_fullStr | Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China |
title_full_unstemmed | Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China |
title_short | Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China |
title_sort | genetic diversity and immunogenicity of the merozoite surface protein 1 c-terminal 19-kda fragment of plasmodium ovale imported from africa into china |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611641/ https://www.ncbi.nlm.nih.gov/pubmed/34819151 http://dx.doi.org/10.1186/s13071-021-05086-6 |
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