title: Naturally Acquired Binding-Inhibitory Antibodies toPlasmodium vivaxDuffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study.
abstract: A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially forPlasmodium vivax(Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events ofPlasmodiuminfection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv andPlasmodium falciparum(Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119versus PfAMA1, Spearman's rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood mononuclear cells from Pv-infected women presented fewer CD8+IFN-γ+T cells and secreted more G-CSF and IL-4 independently of the stimulus usedin vitro. Functional anti-PvDBP levels at recruitment had a positive association with birth weight (difference per doubling antibody levels: 45 g,p-value: 0.046). Thus, naturally acquired binding-inhibitory antibodies to PvDBP might confer protection against poor outcomes of Pv malaria in pregnancy.
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona, Catalonia , Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Requena
authors.affiliation: Caucaseco Scientific Research Center, Universidad del Valle , Cali , Colombia.
authors.forename: Myriam
authors.initials: M
authors.lastname: Arévalo-Herrera
authors.affiliation: Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Menegon
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil; Instituto Leônidas e Maria Deane (ILMD/Fiocruz Amazonia), Amazonia, Brazil.
authors.forename: Flor E
authors.initials: FE
authors.lastname: Martínez-Espinosa
authors.affiliation: Centro de Estudios en Salud, Universidad del Valle de Guatemala , Guatemala City , Guatemala.
authors.forename: Norma
authors.initials: N
authors.lastname: Padilla
authors.affiliation: Instituto Leônidas e Maria Deane (ILMD/Fiocruz Amazonia), Amazonia, Brazil; Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Bôtto-Menezes
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Amazonas , Manaus , Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Malheiro
authors.affiliation: International Center for Genetic Engineering and Biotechnology , Delhi , India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Hans
authors.affiliation: Centro de Estudios en Salud, Universidad del Valle de Guatemala , Guatemala City , Guatemala.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Castellanos
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Macfarlane Burnet Institute of Medical Research, Melbourne, VIC, Australia; Walter and Eliza Hall Institute, Parkville, VIC, Australia.
authors.forename: Leanne
authors.initials: L
authors.lastname: Robinson
authors.affiliation: Papua New Guinea Institute of Medical Research , Madang , Papua New Guinea.
authors.forename: Paula
authors.initials: P
authors.lastname: Samol
authors.affiliation: Medical College Bikaner , Bikaner, Rajasthan , India.
authors.forename: Swati
authors.initials: S
authors.lastname: Kochar
authors.affiliation: Medical College Bikaner , Bikaner, Rajasthan , India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Kochar
authors.affiliation: Medical College Bikaner , Bikaner, Rajasthan , India.
authors.forename: Dhanpat K
authors.initials: DK
authors.lastname: Kochar
authors.affiliation: Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria, Malaria Branch , Atlanta, GA , USA.
authors.forename: Meghna
authors.initials: M
authors.lastname: Desai
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona, Catalonia , Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona, Catalonia , Spain.
authors.forename: Llorenç
authors.initials: L
authors.lastname: Quintó
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona, Catalonia , Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.affiliation: University of Melbourne , Melbourne, VIC , Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rogerson
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Catalonia, Spain; Walter and Eliza Hall Institute, Parkville, VIC, Australia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Severini
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Catalonia, Spain; ICREA, Barcelona, Spain.
authors.forename: Hernando A
authors.initials: HA
authors.lastname: Del Portillo
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona, Catalonia , Spain.
authors.forename: Azucena
authors.initials: A
authors.lastname: Bardají
authors.affiliation: International Center for Genetic Engineering and Biotechnology , Delhi , India.
authors.forename: Chetan C
authors.initials: CC
authors.lastname: Chitnis
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona, Catalonia , Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona, Catalonia , Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
keywords: PvDBP; T cell; antibodies; cytokines; falciparum; immunity; malaria in pregnancy; vivax