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

Komi Gbedande, Nadine Fievet, Firmine Viwami, Sem Ezinmegnon, Saadou Issifou, Jean Philippe Chippaux, Yannelle Dossou, Kabirou Moutairou, Achille Massougbodji, Nicaise Ndam, Willem Adriaan de Jongh, T. Max M. Søgaard, Ali Salanti, Morten A. Nielsen, Meral Esen, Benjamin Mordmüller, Philippe Deloron, Adrian J.F. Luty

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3474-3481
Number of pages8
JournalVaccine
Volume35
Issue number27
DOIs
StatePublished - Jun 14 2017
Externally publishedYes

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Malaria Vaccines
Vaccines
B-lymphocytes
T-lymphocytes
pregnancy
vaccines
B-Lymphocytes
antigens
T-Lymphocytes
Antigens
Pregnancy
Plasmodium falciparum
interleukin-5
Tetanus Toxoid
toxoids
Interleukin-13
Falciparum Malaria
tetanus
Interleukin-5
Infection

Keywords

  • Cytokines
  • Malaria
  • Pregnancy
  • T & B cells
  • Vaccine
  • VAR2CSA

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

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

In: Vaccine, Vol. 35, No. 27, 14.06.2017, p. 3474-3481.

Research output: Contribution to journalArticle

Gbedande, K, Fievet, N, Viwami, F, Ezinmegnon, S, Issifou, S, Chippaux, JP, Dossou, Y, Moutairou, K, Massougbodji, A, Ndam, N, de Jongh, WA, Søgaard, TMM, Salanti, A, Nielsen, MA, Esen, M, Mordmüller, B, Deloron, P & Luty, AJF 2017, 'Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae', Vaccine, vol. 35, no. 27, pp. 3474-3481. https://doi.org/10.1016/j.vaccine.2017.05.027
Gbedande, 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. / Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC : Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae. In: Vaccine. 2017 ; Vol. 35, No. 27. pp. 3474-3481.
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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",
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.",
keywords = "Cytokines, Malaria, Pregnancy, T & B cells, Vaccine, VAR2CSA",
author = "Komi Gbedande and Nadine Fievet and Firmine Viwami and Sem Ezinmegnon and Saadou Issifou and Chippaux, {Jean Philippe} and Yannelle Dossou and Kabirou Moutairou and Achille Massougbodji and Nicaise Ndam and {de Jongh}, {Willem Adriaan} and S{\o}gaard, {T. Max M.} and Ali Salanti and Nielsen, {Morten A.} and Meral Esen and Benjamin Mordm{\"u}ller and Philippe Deloron and Luty, {Adrian J.F.}",
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TY - JOUR

T1 - Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC

T2 - Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae

AU - Gbedande, Komi

AU - Fievet, Nadine

AU - Viwami, Firmine

AU - Ezinmegnon, Sem

AU - Issifou, Saadou

AU - Chippaux, Jean Philippe

AU - Dossou, Yannelle

AU - Moutairou, Kabirou

AU - Massougbodji, Achille

AU - Ndam, Nicaise

AU - de Jongh, Willem Adriaan

AU - Søgaard, T. Max M.

AU - Salanti, Ali

AU - Nielsen, Morten A.

AU - Esen, Meral

AU - Mordmüller, Benjamin

AU - Deloron, Philippe

AU - Luty, Adrian J.F.

PY - 2017/6/14

Y1 - 2017/6/14

N2 - 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.

AB - 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.

KW - Cytokines

KW - Malaria

KW - Pregnancy

KW - T & B cells

KW - Vaccine

KW - VAR2CSA

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