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Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae

Abstract Background The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum . A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC... Full description

Journal Title: Vaccine 2017, Vol.35 (27), p.3474-3481
Main Author: Gbédandé, Komi
Other Authors: Fievet, Nadine , Viwami, Firmine , Ezinmegnon, Sem , Issifou, Saadou , Chippaux, Jean-Philippe , Dossou, Yannelle , Moutairou, Kabirou , Massougbodji, Achille , Ndam, Nicaise , de Jongh, Willem Adriaan , Søgaard, T. Max M , Salanti, Ali , Nielsen, Morten A , Esen, Meral , Mordmüller, Benjamin , Deloron, Philippe , Luty, Adrian J.F
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/28527688
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title: Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae
format: Article
creator:
  • Gbédandé, Komi
  • Fievet, Nadine
  • Viwami, Firmine
  • Ezinmegnon, Sem
  • Issifou, Saadou
  • Chippaux, Jean-Philippe
  • Dossou, Yannelle
  • Moutairou, Kabirou
  • Massougbodji, Achille
  • Ndam, Nicaise
  • de Jongh, Willem Adriaan
  • Søgaard, T. Max M
  • Salanti, Ali
  • Nielsen, Morten A
  • Esen, Meral
  • Mordmüller, Benjamin
  • Deloron, Philippe
  • Luty, Adrian J.F
subjects:
  • Adolescent
  • Adult
  • Allergy and Immunology
  • Antigens
  • Antigens, Protozoan - immunology
  • B cells
  • B-Lymphocytes - immunology
  • Benin
  • Consortia
  • Cytokines
  • Cytokines - secretion
  • Enzyme-linked immunosorbent assay
  • Enzyme-Linked Immunospot Assay
  • Erythrocytes
  • Female
  • Health risks
  • Helper cells
  • Humans
  • Immunological memory
  • Infant, Newborn
  • Inflammation
  • Interferon
  • Interleukin 10
  • Interleukin 13
  • Interleukin 5
  • Interleukin 6
  • Leukocytes (mononuclear)
  • Lymphocytes B
  • Lymphocytes T
  • Malaria
  • Malaria vaccine
  • Malaria Vaccines - immunology
  • Malaria, Falciparum - prevention & control
  • Memory cells
  • Mitogens
  • Parasites
  • Peripheral blood mononuclear cells
  • Placenta
  • Placenta Diseases - prevention & control
  • Plasmodium falciparum
  • Pregnancy
  • Pregnancy Complications, Infectious - prevention & control
  • T & B cells
  • T cells
  • T-Lymphocytes - immunology
  • Tetanus
  • Tumor necrosis factor
  • Vaccine
  • Vaccines
  • VAR2CSA
  • Womens health
  • Young Adult
ispartof: Vaccine, 2017, Vol.35 (27), p.3474-3481
description: Abstract Background The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum . A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond. Methods Clinical and parasitological histories were compiled from monthly clinic visits. On 4 occasions (first and fifth month of pregnancy, delivery, 6 months post-delivery) peripheral blood mononuclear cells were isolated for in vitro assays. PAMVAC-specific memory B cells as well as those specific for a PAM unrelated P. falciparum antigen (PfEMP1-CIDR1a) and for tetanus toxoid were quantified by ELISpot. Memory T cell responses were assessed by quantifying cytokines (IL-5, IL-6, IL-10, IL-13, IFN-γ, TNF-α) in supernatants of cells stimulated in vitro either with PAMVAC, or mitogen (PHA). Results Both tetanus toxoid- and PAMVAC-specific memory B cell frequencies increased to reach peak levels in the 5th month and at delivery, respectively and persisted post-delivery. The frequency of CIDR1a-specific memory B cells was stable during pregnancy, but declined post-delivery. The cumulated prevalence of infection with P. falciparum during pregnancy was 61% by microscopy. In women with a history of such infections, a significantly higher frequency of PAMVAC-specific memory B cells was observed at delivery. PAMVAC-specific pro-inflammatory (IFN-γ, TNF) responses tended to be higher at delivery in those with a history of infection. Mitogen-induced IL-5/IL-13 responses were significantly enhanced in the same women. Conclusions PAMVAC-specific memory B cells are induced during first pregnancies and are maintained post-delivery. Women with a T helper cell profile biased towards production of Th2-type cytokines have a greater risk of infection with P. falciparum.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleClinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae
sourceAlma/SFX Local Collection
creatorGbédandé, Komi ; Fievet, Nadine ; Viwami, Firmine ; Ezinmegnon, Sem ; Issifou, Saadou ; Chippaux, Jean-Philippe ; Dossou, Yannelle ; Moutairou, Kabirou ; Massougbodji, Achille ; Ndam, Nicaise ; de Jongh, Willem Adriaan ; Søgaard, T. Max M ; Salanti, Ali ; Nielsen, Morten A ; Esen, Meral ; Mordmüller, Benjamin ; Deloron, Philippe ; Luty, Adrian J.F
creatorcontribGbédandé, Komi ; Fievet, Nadine ; Viwami, Firmine ; Ezinmegnon, Sem ; Issifou, Saadou ; Chippaux, Jean-Philippe ; Dossou, Yannelle ; Moutairou, Kabirou ; Massougbodji, Achille ; Ndam, Nicaise ; de Jongh, Willem Adriaan ; Søgaard, T. Max M ; Salanti, Ali ; Nielsen, Morten A ; Esen, Meral ; Mordmüller, Benjamin ; Deloron, Philippe ; Luty, Adrian J.F ; Multi-centre research paper
descriptionAbstract Background The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum . A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond. Methods Clinical and parasitological histories were compiled from monthly clinic visits. On 4 occasions (first and fifth month of pregnancy, delivery, 6 months post-delivery) peripheral blood mononuclear cells were isolated for in vitro assays. PAMVAC-specific memory B cells as well as those specific for a PAM unrelated P. falciparum antigen (PfEMP1-CIDR1a) and for tetanus toxoid were quantified by ELISpot. Memory T cell responses were assessed by quantifying cytokines (IL-5, IL-6, IL-10, IL-13, IFN-γ, TNF-α) in supernatants of cells stimulated in vitro either with PAMVAC, or mitogen (PHA). Results Both tetanus toxoid- and PAMVAC-specific memory B cell frequencies increased to reach peak levels in the 5th month and at delivery, respectively and persisted post-delivery. The frequency of CIDR1a-specific memory B cells was stable during pregnancy, but declined post-delivery. The cumulated prevalence of infection with P. falciparum during pregnancy was 61% by microscopy. In women with a history of such infections, a significantly higher frequency of PAMVAC-specific memory B cells was observed at delivery. PAMVAC-specific pro-inflammatory (IFN-γ, TNF) responses tended to be higher at delivery in those with a history of infection. Mitogen-induced IL-5/IL-13 responses were significantly enhanced in the same women. Conclusions PAMVAC-specific memory B cells are induced during first pregnancies and are maintained post-delivery. Women with a T helper cell profile biased towards production of Th2-type cytokines have a greater risk of infection with P. falciparum.
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1EISSN: 1873-2518
2DOI: 10.1016/j.vaccine.2017.05.027
3PMID: 28527688
languageeng
publisherNetherlands: Elsevier Ltd
subjectAdolescent ; Adult ; Allergy and Immunology ; Antigens ; Antigens, Protozoan - immunology ; B cells ; B-Lymphocytes - immunology ; Benin ; Consortia ; Cytokines ; Cytokines - secretion ; Enzyme-linked immunosorbent assay ; Enzyme-Linked Immunospot Assay ; Erythrocytes ; Female ; Health risks ; Helper cells ; Humans ; Immunological memory ; Infant, Newborn ; Inflammation ; Interferon ; Interleukin 10 ; Interleukin 13 ; Interleukin 5 ; Interleukin 6 ; Leukocytes (mononuclear) ; Lymphocytes B ; Lymphocytes T ; Malaria ; Malaria vaccine ; Malaria Vaccines - immunology ; Malaria, Falciparum - prevention & control ; Memory cells ; Mitogens ; Parasites ; Peripheral blood mononuclear cells ; Placenta ; Placenta Diseases - prevention & control ; Plasmodium falciparum ; Pregnancy ; Pregnancy Complications, Infectious - prevention & control ; T & B cells ; T cells ; T-Lymphocytes - immunology ; Tetanus ; Tumor necrosis factor ; Vaccine ; Vaccines ; VAR2CSA ; Womens health ; Young Adult
ispartofVaccine, 2017, Vol.35 (27), p.3474-3481
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1Copyright © 2017 Elsevier Ltd. All rights reserved.
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0Gbédandé, Komi
1Fievet, Nadine
2Viwami, Firmine
3Ezinmegnon, Sem
4Issifou, Saadou
5Chippaux, Jean-Philippe
6Dossou, Yannelle
7Moutairou, Kabirou
8Massougbodji, Achille
9Ndam, Nicaise
10de Jongh, Willem Adriaan
11Søgaard, T. Max M
12Salanti, Ali
13Nielsen, Morten A
14Esen, Meral
15Mordmüller, Benjamin
16Deloron, Philippe
17Luty, Adrian J.F
18Multi-centre research paper
title
0Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae
1Vaccine
addtitleVaccine
descriptionAbstract Background The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum . A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond. Methods Clinical and parasitological histories were compiled from monthly clinic visits. On 4 occasions (first and fifth month of pregnancy, delivery, 6 months post-delivery) peripheral blood mononuclear cells were isolated for in vitro assays. PAMVAC-specific memory B cells as well as those specific for a PAM unrelated P. falciparum antigen (PfEMP1-CIDR1a) and for tetanus toxoid were quantified by ELISpot. Memory T cell responses were assessed by quantifying cytokines (IL-5, IL-6, IL-10, IL-13, IFN-γ, TNF-α) in supernatants of cells stimulated in vitro either with PAMVAC, or mitogen (PHA). Results Both tetanus toxoid- and PAMVAC-specific memory B cell frequencies increased to reach peak levels in the 5th month and at delivery, respectively and persisted post-delivery. The frequency of CIDR1a-specific memory B cells was stable during pregnancy, but declined post-delivery. The cumulated prevalence of infection with P. falciparum during pregnancy was 61% by microscopy. In women with a history of such infections, a significantly higher frequency of PAMVAC-specific memory B cells was observed at delivery. PAMVAC-specific pro-inflammatory (IFN-γ, TNF) responses tended to be higher at delivery in those with a history of infection. Mitogen-induced IL-5/IL-13 responses were significantly enhanced in the same women. Conclusions PAMVAC-specific memory B cells are induced during first pregnancies and are maintained post-delivery. Women with a T helper cell profile biased towards production of Th2-type cytokines have a greater risk of infection with P. falciparum.
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2Allergy and Immunology
3Antigens
4Antigens, Protozoan - immunology
5B cells
6B-Lymphocytes - immunology
7Benin
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11Enzyme-linked immunosorbent assay
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13Erythrocytes
14Female
15Health risks
16Helper cells
17Humans
18Immunological memory
19Infant, Newborn
20Inflammation
21Interferon
22Interleukin 10
23Interleukin 13
24Interleukin 5
25Interleukin 6
26Leukocytes (mononuclear)
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29Malaria
30Malaria vaccine
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32Malaria, Falciparum - prevention & control
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36Peripheral blood mononuclear cells
37Placenta
38Placenta Diseases - prevention & control
39Plasmodium falciparum
40Pregnancy
41Pregnancy Complications, Infectious - prevention & control
42T & B cells
43T cells
44T-Lymphocytes - immunology
45Tetanus
46Tumor necrosis factor
47Vaccine
48Vaccines
49VAR2CSA
50Womens health
51Young Adult
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7Moutairou, Kabirou
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titleClinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae
authorGbédandé, Komi ; Fievet, Nadine ; Viwami, Firmine ; Ezinmegnon, Sem ; Issifou, Saadou ; Chippaux, Jean-Philippe ; Dossou, Yannelle ; Moutairou, Kabirou ; Massougbodji, Achille ; Ndam, Nicaise ; de Jongh, Willem Adriaan ; Søgaard, T. Max M ; Salanti, Ali ; Nielsen, Morten A ; Esen, Meral ; Mordmüller, Benjamin ; Deloron, Philippe ; Luty, Adrian J.F
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7Benin
8Consortia
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35Parasites
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38Placenta Diseases - prevention & control
39Plasmodium falciparum
40Pregnancy
41Pregnancy Complications, Infectious - prevention & control
42T & B cells
43T cells
44T-Lymphocytes - immunology
45Tetanus
46Tumor necrosis factor
47Vaccine
48Vaccines
49VAR2CSA
50Womens health
51Young Adult
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7Moutairou, Kabirou
8Massougbodji, Achille
9Ndam, Nicaise
10de Jongh, Willem Adriaan
11Søgaard, T. Max M
12Salanti, Ali
13Nielsen, Morten A
14Esen, Meral
15Mordmüller, Benjamin
16Deloron, Philippe
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0Gbédandé, Komi
1Fievet, Nadine
2Viwami, Firmine
3Ezinmegnon, Sem
4Issifou, Saadou
5Chippaux, Jean-Philippe
6Dossou, Yannelle
7Moutairou, Kabirou
8Massougbodji, Achille
9Ndam, Nicaise
10de Jongh, Willem Adriaan
11Søgaard, T. Max M
12Salanti, Ali
13Nielsen, Morten A
14Esen, Meral
15Mordmüller, Benjamin
16Deloron, Philippe
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atitleClinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae
jtitleVaccine
addtitleVaccine
date2017
risdate2017
volume35
issue27
spage3474
epage3481
pages3474-3481
issn0264-410X
eissn1873-2518
abstractAbstract Background The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum . A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond. Methods Clinical and parasitological histories were compiled from monthly clinic visits. On 4 occasions (first and fifth month of pregnancy, delivery, 6 months post-delivery) peripheral blood mononuclear cells were isolated for in vitro assays. PAMVAC-specific memory B cells as well as those specific for a PAM unrelated P. falciparum antigen (PfEMP1-CIDR1a) and for tetanus toxoid were quantified by ELISpot. Memory T cell responses were assessed by quantifying cytokines (IL-5, IL-6, IL-10, IL-13, IFN-γ, TNF-α) in supernatants of cells stimulated in vitro either with PAMVAC, or mitogen (PHA). Results Both tetanus toxoid- and PAMVAC-specific memory B cell frequencies increased to reach peak levels in the 5th month and at delivery, respectively and persisted post-delivery. The frequency of CIDR1a-specific memory B cells was stable during pregnancy, but declined post-delivery. The cumulated prevalence of infection with P. falciparum during pregnancy was 61% by microscopy. In women with a history of such infections, a significantly higher frequency of PAMVAC-specific memory B cells was observed at delivery. PAMVAC-specific pro-inflammatory (IFN-γ, TNF) responses tended to be higher at delivery in those with a history of infection. Mitogen-induced IL-5/IL-13 responses were significantly enhanced in the same women. Conclusions PAMVAC-specific memory B cells are induced during first pregnancies and are maintained post-delivery. Women with a T helper cell profile biased towards production of Th2-type cytokines have a greater risk of infection with P. falciparum.
copNetherlands
pubElsevier Ltd
pmid28527688
doi10.1016/j.vaccine.2017.05.027