Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae

Komi Gbedande, Nadine Fievet, Firmine Viwami, Sem Ezinmegnon, Saadou Issifou, Jean Philippe Chippaux, Yannelle Dossou, Kabirou Moutairou, Achille Massougbodji, Nicaise Ndam, Willem Adriaan de Jongh, T. Max M. Søgaard, Ali Salanti, Morten A. Nielsen, Meral Esen, Benjamin Mordmüller, Philippe Deloron, Adrian J.F. Luty

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3474-3481
Number of pages8
JournalVaccine
Volume35
Issue number27
DOIs
StatePublished - Jun 14 2017
Externally publishedYes

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Keywords

  • Cytokines
  • Malaria
  • Pregnancy
  • T & B cells
  • Vaccine
  • VAR2CSA

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Gbedande, K., Fievet, N., Viwami, F., Ezinmegnon, S., Issifou, S., Chippaux, J. P., Dossou, Y., Moutairou, K., Massougbodji, A., Ndam, N., de Jongh, W. A., Søgaard, T. M. M., Salanti, A., Nielsen, M. A., Esen, M., Mordmüller, B., Deloron, P., & Luty, A. J. F. (2017). Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae. Vaccine, 35(27), 3474-3481. https://doi.org/10.1016/j.vaccine.2017.05.027