%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Gbedande, K.
%A Fievet, Nadine
%A Viwami, F.
%A Ezinmegnon, S.
%A Issifou, S.
%A Chippaux, Jean-Philippe
%A Dossou, Y.
%A Moutairou, K.
%A Massougbodji, A.
%A Ndam, N.
%A de Jongh, W. A.
%A Sogaard, T. M. M.
%A Salanti, A.
%A Nielsen, M. A.
%A Esen, M.
%A Mordmuller, B.
%A Deloron, Philippe
%A Luty, Adrian
%A Multi-Centre Research Paper
%T Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC : quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae
%D 2017
%L fdi:010070257
%G ENG
%J Vaccine
%@ 0264-410X
%K Malaria ; Pregnancy ; VAR2CSA ; Vaccine ; Cytokines ; T & B cells
%K BENIN
%M ISI:000403627000009
%N 27
%P 3474-3481
%R 10.1016/j.vaccine.2017.05.027
%U https://www.documentation.ird.fr/hor/fdi:010070257
%> https://www.documentation.ird.fr/intranet/publi/2017/07/010070257.pdf
%V 35
%W Horizon (IRD)
%X 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 PAMVACs 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-gamma, TNF-alpha) 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-gamma, 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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