Gbedande K. auteur aut IRD Fievet Nadine auteur aut IRD Viwami F. auteur aut IRD Ezinmegnon S. auteur aut IRD Issifou S. auteur aut IRD Chippaux Jean-Philippe auteur aut IRD Dossou Y. auteur aut IRD Moutairou K. auteur aut IRD Massougbodji A. auteur aut IRD Ndam N. auteur aut IRD de Jongh W. A. auteur aut IRD Sogaard T. M. M. auteur aut IRD Salanti A. auteur aut IRD Nielsen M. A. auteur aut IRD Esen M. auteur aut IRD Mordmuller B. auteur aut IRD Deloron Philippe auteur aut IRD Luty Adrian auteur aut IRD Multi-Centre Research Paper auteur aut IRD text journalArticle eng text/pdf born digital access 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. specialized Malaria Pregnancy VAR2CSA Vaccine Cytokines T & B cells BENIN 052 050 35 27 3474-3481 2017 0264-410X https://www.documentation.ird.fr/hor/fdi:010070257 10.1016/j.vaccine.2017.05.027 0264-410X [F B010070257] https://www.documentation.ird.fr/hor/fdi:010070257 https://www.documentation.ird.fr/intranet/publi/2017/07/010070257.pdf Accès réservé (Intranet de l'IRD) IRD - Base Horizon / Pleins textes 2017-07-26 2018-01-02 fdi:010070257 fre