Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria

Tonia Woodberry, A PINZON-CHARRY, Kim Piera, Y PANPISUTCHAI, C ENGWERDA, D DOOLAN, E SALWATI, Enny Kenangalem, E TJITRA, Ric Price, M GOOD, Nicholas Anstey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background. The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods. PBMC and plasma collected from malaria-exposed Indonesians during infection and 7-7-28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFN? ELISPOT assay and ELISA. Results: HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-? production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion: The prevalence of acute proliferative and convalescent IFN? responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens. � 2009 Woodberry et al; licensee BioMed Central Ltd.
Original languageEnglish
Pages (from-to)-
JournalMalaria Journal
Volume8
Issue number122
Publication statusPublished - 2009

Fingerprint

Hypoxanthine
Xanthine
Plasmodium
Guanine
Transferases
T-Lymphocytes
Antigens
Malaria
Cell Proliferation
Immunoglobulin G
Infection
Plasmodium yoelii
Acute malaria
Enzyme-Linked Immunospot Assay
Antimalarials
T-Lymphocyte Subsets
Plasmodium falciparum
Epitopes
Parasites
Vaccines

Cite this

Woodberry, Tonia ; PINZON-CHARRY, A ; Piera, Kim ; PANPISUTCHAI, Y ; ENGWERDA, C ; DOOLAN, D ; SALWATI, E ; Kenangalem, Enny ; TJITRA, E ; Price, Ric ; GOOD, M ; Anstey, Nicholas. / Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria. In: Malaria Journal. 2009 ; Vol. 8, No. 122. pp. -.
@article{b433593646e44ac386ded5bbfe23b8d4,
title = "Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria",
abstract = "Background. The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods. PBMC and plasma collected from malaria-exposed Indonesians during infection and 7-7-28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFN? ELISPOT assay and ELISA. Results: HGXPRT-specific T cell proliferation was found in 44{\%} of patients during acute infection; in 80{\%} of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-? production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion: The prevalence of acute proliferative and convalescent IFN? responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens. � 2009 Woodberry et al; licensee BioMed Central Ltd.",
keywords = "cytokine, gamma interferon, hypoxanthine guanine xanthine phosphoribosyl transferase, immunoglobulin G, phosphoribosyltransferase, unclassified drug, glycosyltransferase, hypoxanthine guanine xanthine phosphoribosyltransferase, hypoxanthine-guanine-xanthine phosphoribosyltransferase, protozoal protein, acute disease, adolescent, adult, aged, antibody response, article, CD4+ T lymphocyte, CD8+ T lymphocyte, cell proliferation, cellular immunity, child, controlled study, convalescence, cytokine production, cytokine release, enzyme linked immunosorbent assay, enzyme linked immunospot assay, female, human, Indonesia, major clinical study, malaria, male, nonhuman, nucleotide sequence, peripheral blood mononuclear cell, Plasmodium, school child, sequence analysis, T lymphocyte, amino acid sequence, animal, cell culture, immunology, malaria falciparum, middle aged, molecular genetics, mononuclear cell, mouse, Plasmodium falciparum, preschool child, secretion, sequence alignment, T lymphocyte subpopulation, Adolescent, Adult, Amino Acid Sequence, Animals, Cell Proliferation, Cells, Cultured, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Female, Humans, Interferon-gamma, Leukocytes, Mononuclear, Malaria, Falciparum, Male, Mice, Middle Aged, Molecular Sequence Data, Pentosyltransferases, Protozoan Proteins, Sequence Alignment, T-Lymphocyte Subsets, Young Adult",
author = "Tonia Woodberry and A PINZON-CHARRY and Kim Piera and Y PANPISUTCHAI and C ENGWERDA and D DOOLAN and E SALWATI and Enny Kenangalem and E TJITRA and Ric Price and M GOOD and Nicholas Anstey",
year = "2009",
language = "English",
volume = "8",
pages = "--",
journal = "Malaria Journal",
issn = "1475-2875",
publisher = "BioMed Central",
number = "122",

}

Woodberry, T, PINZON-CHARRY, A, Piera, K, PANPISUTCHAI, Y, ENGWERDA, C, DOOLAN, D, SALWATI, E, Kenangalem, E, TJITRA, E, Price, R, GOOD, M & Anstey, N 2009, 'Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria', Malaria Journal, vol. 8, no. 122, pp. -.

Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria. / Woodberry, Tonia; PINZON-CHARRY, A; Piera, Kim; PANPISUTCHAI, Y; ENGWERDA, C; DOOLAN, D; SALWATI, E; Kenangalem, Enny; TJITRA, E; Price, Ric; GOOD, M; Anstey, Nicholas.

In: Malaria Journal, Vol. 8, No. 122, 2009, p. -.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) in acute malaria

AU - Woodberry, Tonia

AU - PINZON-CHARRY, A

AU - Piera, Kim

AU - PANPISUTCHAI, Y

AU - ENGWERDA, C

AU - DOOLAN, D

AU - SALWATI, E

AU - Kenangalem, Enny

AU - TJITRA, E

AU - Price, Ric

AU - GOOD, M

AU - Anstey, Nicholas

PY - 2009

Y1 - 2009

N2 - Background. The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods. PBMC and plasma collected from malaria-exposed Indonesians during infection and 7-7-28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFN? ELISPOT assay and ELISA. Results: HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-? production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion: The prevalence of acute proliferative and convalescent IFN? responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens. � 2009 Woodberry et al; licensee BioMed Central Ltd.

AB - Background. The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods. PBMC and plasma collected from malaria-exposed Indonesians during infection and 7-7-28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFN? ELISPOT assay and ELISA. Results: HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-? production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion: The prevalence of acute proliferative and convalescent IFN? responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens. � 2009 Woodberry et al; licensee BioMed Central Ltd.

KW - cytokine

KW - gamma interferon

KW - hypoxanthine guanine xanthine phosphoribosyl transferase

KW - immunoglobulin G

KW - phosphoribosyltransferase

KW - unclassified drug

KW - glycosyltransferase

KW - hypoxanthine guanine xanthine phosphoribosyltransferase

KW - hypoxanthine-guanine-xanthine phosphoribosyltransferase

KW - protozoal protein

KW - acute disease

KW - adolescent

KW - adult

KW - aged

KW - antibody response

KW - article

KW - CD4+ T lymphocyte

KW - CD8+ T lymphocyte

KW - cell proliferation

KW - cellular immunity

KW - child

KW - controlled study

KW - convalescence

KW - cytokine production

KW - cytokine release

KW - enzyme linked immunosorbent assay

KW - enzyme linked immunospot assay

KW - female

KW - human

KW - Indonesia

KW - major clinical study

KW - malaria

KW - male

KW - nonhuman

KW - nucleotide sequence

KW - peripheral blood mononuclear cell

KW - Plasmodium

KW - school child

KW - sequence analysis

KW - T lymphocyte

KW - amino acid sequence

KW - animal

KW - cell culture

KW - immunology

KW - malaria falciparum

KW - middle aged

KW - molecular genetics

KW - mononuclear cell

KW - mouse

KW - Plasmodium falciparum

KW - preschool child

KW - secretion

KW - sequence alignment

KW - T lymphocyte subpopulation

KW - Adolescent

KW - Adult

KW - Amino Acid Sequence

KW - Animals

KW - Cell Proliferation

KW - Cells, Cultured

KW - Child

KW - Child, Preschool

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Humans

KW - Interferon-gamma

KW - Leukocytes, Mononuclear

KW - Malaria, Falciparum

KW - Male

KW - Mice

KW - Middle Aged

KW - Molecular Sequence Data

KW - Pentosyltransferases

KW - Protozoan Proteins

KW - Sequence Alignment

KW - T-Lymphocyte Subsets

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=67949112688&partnerID=8YFLogxK

M3 - Article

VL - 8

SP - -

JO - Malaria Journal

JF - Malaria Journal

SN - 1475-2875

IS - 122

ER -