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 -