Antigenicity and immunogenicity of PvRALP1, a novel Plasmodium vivax rhoptry neck protein

Yang Cheng, Jian Li, Daisuke Ito, Deok Hoon Kong, Kwon Soo Ha, Feng Lu, Bo Wang, Jetsumon Sattabongkot, Chae Seung Lim, Takafumi Tsuboi, Eun Taek Han

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1; PVX-096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species. Methods: Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined. Results: Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9% and 55.4% sensitivity and 95.0% and 92.5% specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R <sup>2</sup>∈=∈0.11) or PvRALP1-Tr (R <sup>2</sup>∈=∈0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax. Conclusions: This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites.

Original languageEnglish
Article number186
JournalMalaria Journal
Volume14
Issue number1
DOIs
Publication statusPublished - 2015 Apr 29

Fingerprint

Plasmodium vivax
Neck
Proteins
Merozoites
Plasmodium
Immunoglobulin G
Protein Sorting Signals
Leucine
Glycine
Glutamic Acid
Parasites
Leucine Zippers
Protein Array Analysis
Republic of Korea
Parasitic Diseases
Parasitemia
Cell-Free System
Antibodies
Tight Junctions
Vacuoles

Keywords

  • Antigenicity
  • Immunogenicity
  • Plasmodium vivax
  • RALP1
  • Rhoptry neck protein

ASJC Scopus subject areas

  • Infectious Diseases
  • Parasitology

Cite this

Cheng, Y., Li, J., Ito, D., Kong, D. H., Ha, K. S., Lu, F., ... Han, E. T. (2015). Antigenicity and immunogenicity of PvRALP1, a novel Plasmodium vivax rhoptry neck protein. Malaria Journal, 14(1), [186]. https://doi.org/10.1186/s12936-015-0698-z

Antigenicity and immunogenicity of PvRALP1, a novel Plasmodium vivax rhoptry neck protein. / Cheng, Yang; Li, Jian; Ito, Daisuke; Kong, Deok Hoon; Ha, Kwon Soo; Lu, Feng; Wang, Bo; Sattabongkot, Jetsumon; Lim, Chae Seung; Tsuboi, Takafumi; Han, Eun Taek.

In: Malaria Journal, Vol. 14, No. 1, 186, 29.04.2015.

Research output: Contribution to journalArticle

Cheng, Y, Li, J, Ito, D, Kong, DH, Ha, KS, Lu, F, Wang, B, Sattabongkot, J, Lim, CS, Tsuboi, T & Han, ET 2015, 'Antigenicity and immunogenicity of PvRALP1, a novel Plasmodium vivax rhoptry neck protein', Malaria Journal, vol. 14, no. 1, 186. https://doi.org/10.1186/s12936-015-0698-z
Cheng, Yang ; Li, Jian ; Ito, Daisuke ; Kong, Deok Hoon ; Ha, Kwon Soo ; Lu, Feng ; Wang, Bo ; Sattabongkot, Jetsumon ; Lim, Chae Seung ; Tsuboi, Takafumi ; Han, Eun Taek. / Antigenicity and immunogenicity of PvRALP1, a novel Plasmodium vivax rhoptry neck protein. In: Malaria Journal. 2015 ; Vol. 14, No. 1.
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abstract = "Background: Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1; PVX-096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species. Methods: Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined. Results: Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9{\%} and 55.4{\%} sensitivity and 95.0{\%} and 92.5{\%} specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R 2∈=∈0.11) or PvRALP1-Tr (R 2∈=∈0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax. Conclusions: This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites.",
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AU - Cheng, Yang

AU - Li, Jian

AU - Ito, Daisuke

AU - Kong, Deok Hoon

AU - Ha, Kwon Soo

AU - Lu, Feng

AU - Wang, Bo

AU - Sattabongkot, Jetsumon

AU - Lim, Chae Seung

AU - Tsuboi, Takafumi

AU - Han, Eun Taek

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N2 - Background: Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1; PVX-096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species. Methods: Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined. Results: Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9% and 55.4% sensitivity and 95.0% and 92.5% specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R 2∈=∈0.11) or PvRALP1-Tr (R 2∈=∈0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax. Conclusions: This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites.

AB - Background: Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1; PVX-096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species. Methods: Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined. Results: Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9% and 55.4% sensitivity and 95.0% and 92.5% specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R 2∈=∈0.11) or PvRALP1-Tr (R 2∈=∈0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax. Conclusions: This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites.

KW - Antigenicity

KW - Immunogenicity

KW - Plasmodium vivax

KW - RALP1

KW - Rhoptry neck protein

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