Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses

Komi Gbedande, Gilles Cottrell, Bertin Vianou, Akanni Adededji Abdoul Ibitokou, Aurax Fernando, Marita Troye-Blomberg, Ali Salanti, Kabirou Moutairou, Achille Massougbodji, Nicaise Tuikue Ndam, Philippe Deloron, Adrian J F Luty, Nadine Fievet

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-γ-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-γ responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-γ responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.

Original languageEnglish (US)
Article number485
JournalMalaria Journal
Volume15
Issue number1
DOIs
StatePublished - Sep 21 2016
Externally publishedYes

Fingerprint

Plasmodium falciparum
Cytokines
T-Lymphocytes
Pregnancy
Infection
Malaria
Gravidity
Peptide T
Interleukin-10
Anemia
Blood Cells
B-Lymphocytes
Cohort Studies
Vaccines
Multivariate Analysis
Antibodies

Keywords

  • Cytokines
  • Malaria
  • Pregnancy
  • T cells
  • VAR2CSA

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses. / Gbedande, Komi; Cottrell, Gilles; Vianou, Bertin; Ibitokou, Akanni Adededji Abdoul; Fernando, Aurax; Troye-Blomberg, Marita; Salanti, Ali; Moutairou, Kabirou; Massougbodji, Achille; Ndam, Nicaise Tuikue; Deloron, Philippe; Luty, Adrian J F; Fievet, Nadine.

In: Malaria Journal, Vol. 15, No. 1, 485, 21.09.2016.

Research output: Contribution to journalArticle

Gbedande, K, Cottrell, G, Vianou, B, Ibitokou, AAA, Fernando, A, Troye-Blomberg, M, Salanti, A, Moutairou, K, Massougbodji, A, Ndam, NT, Deloron, P, Luty, AJF & Fievet, N 2016, 'Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses', Malaria Journal, vol. 15, no. 1, 485. https://doi.org/10.1186/s12936-016-1525-x
Gbedande, Komi ; Cottrell, Gilles ; Vianou, Bertin ; Ibitokou, Akanni Adededji Abdoul ; Fernando, Aurax ; Troye-Blomberg, Marita ; Salanti, Ali ; Moutairou, Kabirou ; Massougbodji, Achille ; Ndam, Nicaise Tuikue ; Deloron, Philippe ; Luty, Adrian J F ; Fievet, Nadine. / Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses. In: Malaria Journal. 2016 ; Vol. 15, No. 1.
@article{ed514e5225fa49fdab43211351050eef,
title = "Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses",
abstract = "Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-γ-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-γ responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-γ responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.",
keywords = "Cytokines, Malaria, Pregnancy, T cells, VAR2CSA",
author = "Komi Gbedande and Gilles Cottrell and Bertin Vianou and Ibitokou, {Akanni Adededji Abdoul} and Aurax Fernando and Marita Troye-Blomberg and Ali Salanti and Kabirou Moutairou and Achille Massougbodji and Ndam, {Nicaise Tuikue} and Philippe Deloron and Luty, {Adrian J F} and Nadine Fievet",
year = "2016",
month = "9",
day = "21",
doi = "10.1186/s12936-016-1525-x",
language = "English (US)",
volume = "15",
journal = "Malaria Journal",
issn = "1475-2875",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses

AU - Gbedande, Komi

AU - Cottrell, Gilles

AU - Vianou, Bertin

AU - Ibitokou, Akanni Adededji Abdoul

AU - Fernando, Aurax

AU - Troye-Blomberg, Marita

AU - Salanti, Ali

AU - Moutairou, Kabirou

AU - Massougbodji, Achille

AU - Ndam, Nicaise Tuikue

AU - Deloron, Philippe

AU - Luty, Adrian J F

AU - Fievet, Nadine

PY - 2016/9/21

Y1 - 2016/9/21

N2 - Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-γ-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-γ responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-γ responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.

AB - Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-γ-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-γ responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-γ responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.

KW - Cytokines

KW - Malaria

KW - Pregnancy

KW - T cells

KW - VAR2CSA

UR - http://www.scopus.com/inward/record.url?scp=84988322708&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84988322708&partnerID=8YFLogxK

U2 - 10.1186/s12936-016-1525-x

DO - 10.1186/s12936-016-1525-x

M3 - Article

AN - SCOPUS:84988322708

VL - 15

JO - Malaria Journal

JF - Malaria Journal

SN - 1475-2875

IS - 1

M1 - 485

ER -