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

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, 6months 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.

• Authors: Komi Gbédandé, 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, Multi-centre research paper
• Journal: Vaccine (Vaccine) Vol. 35 Issue 27 Pg. 3474-3481 (06 14 2017) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 28527688 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Protozoan
• Cytokines
• Malaria Vaccines
• VAR2CSA protein, Plasmodium falciparum

Topics

• Adolescent
• Adult
• Antigens, Protozoan (immunology)
• B-Lymphocytes (immunology)
• Benin
• Cytokines (metabolism)
• Enzyme-Linked Immunospot Assay
• Female
• Humans
• Infant, Newborn
• Malaria Vaccines (immunology)
• Malaria, Falciparum (prevention & control)
• Placenta Diseases (prevention & control)
• Pregnancy
• Pregnancy Complications, Infectious (prevention & control)
• T-Lymphocytes (immunology)
• Young Adult