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

Komi Gbédandé; Nadine Fievet; Firmine Viwami; Sèm Ezinmègnon; Saadou Issifou; Jean-Philippe Chippaux; Yannelle Dossou; Kabirou Moutairou; Achille Massougbodji; Nicaise T Ndam; Willem Adriaan De Jongh; T. Max M. Søgaard; Ali Salanti; Morten A. Nielsen; Meral Esen; Benjamin Mordmüller; Philippe Deloron; Adrian J F Luty

doi:10.1016/j.vaccine.2017.05.027

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

Komi Gbédandé, Nadine Fievet^*, Firmine Viwami, Sèm Ezinmègnon, Saadou Issifou, Jean-Philippe Chippaux, Yannelle Dossou, Kabirou Moutairou, Achille Massougbodji, Nicaise T Ndam, Willem Adriaan De Jongh, T. Max M. Søgaard, Ali Salanti, Morten A. Nielsen, Meral Esen, Benjamin Mordmüller, Philippe Deloron, Adrian J F Luty

^*Corresponding author af dette arbejde

VAR2CSA team

11 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Vaccine
Vol/bind	35
Udgave nummer	27
Sider (fra-til)	3474-3481
Antal sider	8
ISSN	0264-410X
DOI	https://doi.org/10.1016/j.vaccine.2017.05.027
Status	Udgivet - 2017

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10.1016/j.vaccine.2017.05.027

Citationsformater

Gbédandé, K., Fievet, N., Viwami, F., Ezinmègnon, S., Issifou, S., Chippaux, J-P., Dossou, Y., Moutairou, K., Massougbodji, A., Ndam, N. T., De Jongh, W. A., Søgaard, T. M. M., Salanti, A., Nielsen, M. A., Esen, M., Mordmüller, B., Deloron, P., & Luty, A. J. F. (2017). Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae. Vaccine, 35(27), 3474-3481. https://doi.org/10.1016/j.vaccine.2017.05.027

Gbédandé, K, Fievet, N, Viwami, F, Ezinmègnon, S, Issifou, S, Chippaux, J-P, Dossou, Y, Moutairou, K, Massougbodji, A, Ndam, NT, 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, bind 35, nr. 27, s. 3474-3481. https://doi.org/10.1016/j.vaccine.2017.05.027

@article{f6986b5b82df4412a98e17803bf16889,

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 Gb{\'e}dand{\'e} and Nadine Fievet and Firmine Viwami and S{\`e}m Ezinm{\`e}gnon and Saadou Issifou and Jean-Philippe Chippaux and Yannelle Dossou and Kabirou Moutairou and Achille Massougbodji and Ndam, {Nicaise T} 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}",

year = "2017",

doi = "10.1016/j.vaccine.2017.05.027",

language = "English",

volume = "35",

pages = "3474--3481",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier",

number = "27",

}

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 - Gbédandé, Komi

AU - Fievet, Nadine

AU - Viwami, Firmine

AU - Ezinmègnon, Sèm

AU - Issifou, Saadou

AU - Chippaux, Jean-Philippe

AU - Dossou, Yannelle

AU - Moutairou, Kabirou

AU - Massougbodji, Achille

AU - Ndam, Nicaise T

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

Y1 - 2017

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

U2 - 10.1016/j.vaccine.2017.05.027

DO - 10.1016/j.vaccine.2017.05.027

M3 - Journal article

C2 - 28527688

AN - SCOPUS:85019875679

SN - 0264-410X

VL - 35

SP - 3474

EP - 3481

JO - Vaccine

JF - Vaccine

IS - 27

ER -

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

Abstract

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