Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae. Issue 27 (14th June 2017)

• Record Type: Journal Article
• Authors: Gbédandé, Komi; Fievet, Nadine; Viwami, Firmine; Ezinmegnon, Sem; Issifou, Saadou; Chippaux, Jean-Philippe; Dossou, Yannelle; Moutairou, Kabirou; Massougbodji, Achille; Ndam, Nicaise; de Jongh, Willem Adriaan; Søgaard, T. Max M.; Salanti, Ali; Nielsen, Morten A.; Esen, Meral; Mordmüller, Benjamin; Deloron, Philippe; Luty, Adrian J.F.
• Is Part Of: Vaccine. Volume 35:Issue 27(2017)
• Page Start: 3474
• Page End: 3481
• Publication Date: 2017-06-14
• Subjects: ANV antenatal visit -- BD Becton Dickinson -- AEC (3-amino-9-ethylcarbazole) -- CBA cytometric bead array -- CERPAGE Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance -- CPDA citrate phosphate dextrose adenine -- IRD Research Institute for Development, IFN-γ, Interferon gamma -- IL-6 Interleukin-6 -- IL-10 Interleukin-10 -- IL-13 Interleukin -- IPTp intermittent preventive treatment during pregnancy -- LLOD lower limit of detection -- PBMC peripheral blood mononuclear cells -- PHA phytohemagglutinin -- PAM pregnancy-associated malaria -- P. falciparum (Plasmodium falciparum) -- RDT rapid diagnostic test -- SP sulfadoxine-pyrimethamine, PlacMalVac, placental malaria vaccine -- TBS thick blood smear -- TNF tumor necrosis factor -- UI universal unit -- WHO World Health Organization; Malaria -- Pregnancy -- VAR2CSA -- Vaccine -- Cytokines -- T & B cells; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.05.027
• Languages: English
• ISSNs: 0264-410X

Abstract

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.