Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC : quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae Gbedande, K. /Fievet, Nadine Viwami, F. Ezinmegnon, S. Issifou, S. /Chippaux, Jean-Philippe Dossou, Y. Moutairou, K. Massougbodji, A. Ndam, N. de Jongh, W. A. Sogaard, T. M. M. Salanti, A. Nielsen, M. A. Esen, M. Mordmuller, B. /Deloron, Philippe /Luty, Adrian Multi-Centre Research Paper Malaria Pregnancy VAR2CSA Vaccine Cytokines T & B cells 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. 2017 text https://www.documentation.ird.fr/hor/fdi:010070257 fdi:010070257 Gbedande K., Fievet Nadine, Viwami F., Ezinmegnon S., Issifou S., Chippaux Jean-Philippe, Dossou Y., Moutairou K., Massougbodji A., Ndam N., de Jongh W. A., Sogaard T. M. M., Salanti A., Nielsen M. A., Esen M., Mordmuller B., Deloron Philippe, Luty Adrian, Multi-Centre Research Paper. Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC : quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae. 2017, 35 (27), 3474-3481 EN BENIN