Relationship between Human Immunodeficiency Virus Type 1 Coinfection, Anemia, and Levels and Function of Antibodies to Variant Surface Antigens in Pregnancy-Associated Malaria

Jaworowski, Anthony; Fernandes, Liselle; Yosaatmadja, Francisca; Feng, Gaoqian; Mwapasa, Victor; Molyneux, Malcolm E.; Meshnick, Steven R.; Lewis, Jennifer A.; Rogerson, Stephen J.

doi:10.1128/cvi.00356-08

Cited by 38 publications

(51 citation statements)

References 33 publications

(35 reference statements)

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“…IgG1 and IgG3 are the predominant antibody isotypes in placental infections (19), indicating that antibodies may opsonize IEs for phagocytosis as well as to inhibit binding. Although inhibitory antibodies have been correlated with protection in some studies (17,25), this correlation has not been observed in all reports, and opsonizing antibodies have also been proposed to have a protective role (28,29,34). It is not known whether women ever achieve sterile immunity against placental infections, but they do acquire a substantial degree of protective immunity after repeated exposure (12).…”

Section: Discussionmentioning

confidence: 88%

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Immunization with VAR2CSA-DBL5 Recombinant Protein Elicits Broadly Cross-Reactive Antibodies to Placental Plasmodium falciparum -Infected Erythrocytes

et al. 2010

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Pregnancy-associated malaria is a severe clinical syndrome associated with the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, a member of the large and diverse P. falciparum erythrocyte membrane 1 (PfEMP1) protein family. To better understand if conserved regions in VAR2CSA can be targeted by antibodies, we immunized rabbits with VAR2CSA-DBL1 and -DBL5 recombinant proteins produced in Pichia pastoris and developed a panel of seven chondroitin sulfate A (CSA)-binding parasites from diverse geographic origins. Overall, no two parasites in the panel expressed the same VAR2CSA sequence. The DBL1 domains averaged 80% amino acid identity (range, 72 to 89%), and the DBL5 domains averaged 86% amino acid identity (range, 83 to 99%), similar to a broader sampling of VAR2CSA sequences from around the world. Whereas antibodies generated against the VAR2CSA-DBL1 recombinant protein had only limited breadth and reacted with three or four parasites in the panel, immunization with DBL5 recombinant proteins elicited broadly cross-reactive antibodies against all or most parasites in the panel, as well as to fresh clinical isolates from pregnant women. These findings demonstrate that the major PfEMP1 variant expressed by placental isolates exposes strain-transcendent epitopes that can be targeted by vaccination and may have application for pregnancy malaria vaccine development.

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Section: Discussionmentioning

confidence: 88%

“…Over successive pregnancies, women acquire antibodies to the surface antigens expressed by placental IEs, which correlate with improved pregnancy outcomes (7,25,33,44). Antibodies are thought to protect against placental malaria by inhibiting IE binding to CSA (17,25,40,44) or opsonizing IEs for phagocytosis (28,29,34,52).…”

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confidence: 99%

Immunization with VAR2CSA-DBL5 Recombinant Protein Elicits Broadly Cross-Reactive Antibodies to Placental Plasmodium falciparum -Infected Erythrocytes

et al. 2010

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“…In sub-Saharan Africa, 25 million pregnant women are currently at risk for malaria, accounting for 10,000 maternal and 200,000 neonatal deaths per year (Matangila et al, 2014;Mbah et al, 2015). In such regions of high transmission and endemicity, sub-clinical malarial infection is common (Takem and D'Alessandro, 2013) and individuals living in such regions usually develop protective immunity to malaria by adolescence; however, this protection is partially abrogated in women during pregnancy, resulting in pregnancy-associated malaria (PAM) (Jaworowski et al, 2009;Takem and D'Alessandro, 2013). Pregnancy-associated malaria results in tremendous obstetrical and paediatric morbidity, including maternal anaemia, intrauterine growth retardation, low birth weight, prematurity, miscarriage, and stillbirth (Tonga et al, 2013;Mbah et al, 2015;White, 2015; Chedraui, Daily and Wylie, 2016; Prahl et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Peripheral Parasitaemia and Its Association With Plasma Cytokines Levels in Malaria-Infected Pregnant Women in Aba, Abia State, Nigeria

Ifeanyichukwu

Okamgba

Amilo

et al. 2017

AJID

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Background: Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. Materials and Methods: A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. Results:The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). Conclusion:This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied.

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“…These isotypes bind via their Fc domain to Fc␥ receptors, thereby eliciting cellular immune responses of the innate immune system. Antibody opsonization of P. falciparum-infected erythrocytes and merozoites enhances their phagocytosis (6,12,22,30,33,55). The respiratory burst that is elicited by Fc receptor cross-linking furnishes the phagosome with cytotoxic compounds and has been positively associated with protection (20).…”

mentioning

confidence: 99%

Strain-Transcending Fc-Dependent Killing ofPlasmodium falciparumby Merozoite Surface Protein 2 Allele-Specific Human Antibodies

Stubbs¹,

Olugbile

Balam

et al. 2011

Infect Immun

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It is widely accepted that antibody responses against the human parasitic pathogen Plasmodium falciparum protect the host from the rigors of severe malaria and death. However, there is a continuing need for the development of in vitro correlate assays of immune protection. To this end, the capacity of human monoclonal and polyclonal antibodies in eliciting phagocytosis and parasite growth inhibition via Fc␥ receptor-dependent mechanisms was explored. In examining the extent to which sequence diversity in merozoite surface protein 2 (MSP2) results in the evasion of antibody responses, an unexpectedly high level of heterologous function was measured for allele-specific human antibodies. The dependence on Fc␥ receptors for opsonic phagocytosis and monocyte-mediated antibody-dependent parasite inhibition was demonstrated by the mutation of the Fc domain of monoclonal antibodies against both MSP2 and a novel vaccine candidate, peptide 27 from the gene PFF0165c. The described flow cytometry-based functional assays are expected to be useful for assessing immunity in naturally infected and vaccinated individuals and for prioritizing among blood-stage antigens for inclusion in blood-stage vaccines.Merozoite surface protein 2 (MSP2) is a leading Plasmodium falciparum vaccine candidate. Antibody responses to MSP2 have been associated with protection from malaria in humans (1,11,37,43,50,53) and afford protection in mouse models (35,46). However, extreme sequence diversity in MSP2 is considered an obstacle for vaccine design. Hundreds of alleles encoding MSP2 are classified into two main allelic families represented by the 3D7 and FC27/D10 MSP2 sequences (15,28,49,57). The coexistence of parasites bearing the dimorphic alleles at similar frequencies in globally disparate locations indicates their maintenance by selective pressures (9). Given that MSP2 is a blood-stage antigen, it is considered likely that sequence diversification may be driven by the host immune response by allele-specific antibodies. Consistent with this hypothesis, vaccine recipients in the Combination B phase IIb vaccine trial, whose humoral responses against the MSP2-3D7 allele were boosted, were rendered more susceptible than the placebo controls to parasitization with heterologous FC27-type parasites (16,19). Early studies showed that mouse monoclonal antibodies (MAbs) that discriminated between heterologous parasites affected homologous in vitro growth inhibition (7, 13). Curiously, there is scant evidence of the inability of allele-specific MAbs to inhibit heterologous parasites in vitro (45).Like other P. falciparum antigens, MSP2 antibody responses are skewed to cytophilic (IgG1 and IgG3) isotypes (37,43,50,53,54), which have been positively associated with protection from malaria (4,11,21,37,44,50,54). These isotypes bind via their Fc domain to Fc␥ receptors, thereby eliciting cellular immune responses of the innate immune system. Antibody opsonization of P. falciparum-infected erythrocytes and merozoites enhances their phagocytosis (6,12,22,30,3...

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Relationship between Human Immunodeficiency Virus Type 1 Coinfection, Anemia, and Levels and Function of Antibodies to Variant Surface Antigens in Pregnancy-Associated Malaria

Cited by 38 publications

References 33 publications

Immunization with VAR2CSA-DBL5 Recombinant Protein Elicits Broadly Cross-Reactive Antibodies to Placental Plasmodium falciparum -Infected Erythrocytes

Immunization with VAR2CSA-DBL5 Recombinant Protein Elicits Broadly Cross-Reactive Antibodies to Placental Plasmodium falciparum -Infected Erythrocytes

Peripheral Parasitaemia and Its Association With Plasma Cytokines Levels in Malaria-Infected Pregnant Women in Aba, Abia State, Nigeria

Strain-Transcending Fc-Dependent Killing ofPlasmodium falciparumby Merozoite Surface Protein 2 Allele-Specific Human Antibodies

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