Komi Gbédandé1, Nadine Fievet2, Firmine Viwami3, Sem Ezinmegnon4, Saadou Issifou5, Jean-Philippe Chippaux6, Yannelle Dossou7, Kabirou Moutairou8, Achille Massougbodji9, Nicaise Ndam10, Willem Adriaan de Jongh11, T Max M Søgaard12, Ali Salanti13, Morten A Nielsen14, Meral Esen15, Benjamin Mordmüller16, Philippe Deloron17, Adrian J F Luty18. 1. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; Département de Biochimie et de Biologie Cellulaire, Faculté des Sciences et Techniques, Université d'Abomey-Calavi, Benin; MERIT UMR D216, Institut de Recherche pour le Développement, Université Paris Descartes, COMUE Sorbonne Paris Cité, 75006 Paris, France. Electronic address: gbedande.komi@gmail.com. 2. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; MERIT UMR D216, Institut de Recherche pour le Développement, Université Paris Descartes, COMUE Sorbonne Paris Cité, 75006 Paris, France. Electronic address: nadine.fievet@ird.fr. 3. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin. Electronic address: vfeafr@yahoo.fr. 4. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin. Electronic address: e25sem@yahoo.fr. 5. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin. Electronic address: isaadou2002@yahoo.fr. 6. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; MERIT UMR D216, Institut de Recherche pour le Développement, Université Paris Descartes, COMUE Sorbonne Paris Cité, 75006 Paris, France. Electronic address: jean-philippe.chippaux@ird.fr. 7. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin. Electronic address: akpedossou@gmail.com. 8. Département de Biochimie et de Biologie Cellulaire, Faculté des Sciences et Techniques, Université d'Abomey-Calavi, Benin. Electronic address: kamoutairo@yahoo.fr. 9. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin. Electronic address: massougbodjiachille@yahoo.fr. 10. MERIT UMR D216, Institut de Recherche pour le Développement, Université Paris Descartes, COMUE Sorbonne Paris Cité, 75006 Paris, France. Electronic address: nicaise.ndam@ird.fr. 11. ExpreS(2)ion Biotechnologies SCION-DTU Science Park DK-2970, Hoersholm, Denmark. Electronic address: wdj@expres2ionbio.com. 12. ExpreS(2)ion Biotechnologies SCION-DTU Science Park DK-2970, Hoersholm, Denmark. Electronic address: max@expres2ionbio.com. 13. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. Electronic address: salanti@sund.ku.dk. 14. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. Electronic address: mortenn@sund.ku.dk. 15. Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany. Electronic address: meral.esen@uni-tuebingen.de. 16. Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen, Germany. Electronic address: benjamin.mordmueller@uni-tuebingen.de. 17. MERIT UMR D216, Institut de Recherche pour le Développement, Université Paris Descartes, COMUE Sorbonne Paris Cité, 75006 Paris, France. Electronic address: philippe.deloron@ird.fr. 18. Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance (CERPAGE), Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Benin; MERIT UMR D216, Institut de Recherche pour le Développement, Université Paris Descartes, COMUE Sorbonne Paris Cité, 75006 Paris, France. Electronic address: adrian.luty@ird.fr.
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.
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: C Álvarez-Larrotta; O M Agudelo; Y Duque; K Gavina; S K Yanow; A Maestre; J Carmona-Fonseca; E Arango Journal: Clin Exp Immunol Date: 2018-10-19 Impact factor: 4.330
Authors: Benjamin Mordmüller; Mihály Sulyok; Diane Egger-Adam; Mafalda Resende; Willem A de Jongh; Mette H Jensen; Helle Holm Smedegaard; Sisse B Ditlev; Max Soegaard; Lars Poulsen; Charlotte Dyring; Carlos Lamsfus Calle; Annette Knoblich; Javier Ibáñez; Meral Esen; Philippe Deloron; Nicaise Ndam; Saadou Issifou; Sophie Houard; Randall F Howard; Steven G Reed; Odile Leroy; Adrian J F Luty; Thor G Theander; Peter G Kremsner; Ali Salanti; Morten A Nielsen Journal: Clin Infect Dis Date: 2019-10-15 Impact factor: 9.079
Authors: David Ricardo Salamanca; Marcela Gómez; Anny Camargo; Laura Cuy-Chaparro; Jessica Molina-Franky; César Reyes; Manuel Alfonso Patarroyo; Manuel Elkin Patarroyo Journal: Front Microbiol Date: 2019-12-03 Impact factor: 5.640
Authors: Alexandre Manirakiza; Eugène Serdouma; Richard Norbert Ngbalé; Sandrine Moussa; Samuel Gondjé; Rock Mbetid Degana; Gislain Géraud Banthas Bata; Jean Methode Moyen; Jean Delmont; Gérard Grésenguet; Abdoulaye Sepou Journal: J Public Health Afr Date: 2017-12-31