scholarly journals Antibodies That Inhibit Binding of Plasmodium falciparum-Infected Erythrocytes to Chondroitin Sulfate A and to the C Terminus of Merozoite Surface Protein 1 Correlate with Reduced Placental Malaria in Cameroonian Women

2004 ◽  
Vol 72 (3) ◽  
pp. 1603-1607 ◽  
Author(s):  
Diane Wallace Taylor ◽  
Aniong Zhou ◽  
Lauren E. Marsillio ◽  
Lucy W. Thuita ◽  
Efua B. Leke ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Chondroitin Sulfate ◽  
Placental Malaria ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Liver Stage ◽  
Merozoite Surface Protein 1 ◽  
Erythrocyte Surface ◽  
Antibody Levels ◽  
Chondroitin Sulfate A

ABSTRACT Plasmodium falciparum-infected erythrocytes often sequester in the placenta of pregnant women, producing placental malaria, a condition that can compromise the health of the developing fetus. Scientists are hopeful that a vaccine can be developed to prevent this condition. Immunological mechanisms responsible for eliminating parasites from the placenta remain unclear, but antibodies to the carboxyl-terminal 19-kDa segment of the merozoite surface protein 1 (MSP1-19), the ring-infected erythrocyte surface antigen (RESA), and an erythrocyte-surface ligand that binds chondroitin sulfate A (CSA-L) have been implicated. In addition, antibodies to sporozoite and liver-stage antigens could reduce initial parasite burdens. This study sought to determine if antibodies to the circumsporozoite protein (CSP), liver-stage antigen 1 (LSA1), RESA, MSP1-19, or CSA-L correlated with either the absence of placental parasites or low placental parasitemias. Using a frequency-matched case-control study design, we compared antibody levels in women (gravidity 1 to 11) with and without placental malaria. Results showed that women who were antibody negative for MSP1-19 were at a higher risk of having placental malaria than women with antibodies (P < 0.007). Furthermore, an association between high levels of antibodies that blocked the binding of infected erythrocytes to CSA and low placental parasitemias was observed (P = 0.02). On the other hand, women with high antibody levels at term to CSP, LSA1, and RESA were more likely to have placental malaria than antibody-negative women. Since antibodies to MSP1-19 and CSA-L were associated with reduced placental malaria, both antigens show promise for inclusion in a vaccine for women of child-bearing age.

scholarly journals High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission

2012 ◽  
Vol 80 (4) ◽  
pp. 1479-1490 ◽  
Author(s):  
Yeung L. Tutterrow ◽  
Marion Avril ◽  
Kavita Singh ◽  
Carole A. Long ◽  
Robert J. Leke ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Chondroitin Sulfate ◽  
Malaria Transmission ◽  
Placental Malaria ◽  
Plasma Samples ◽  
High Antibody ◽  
Allelic Variants ◽  
Increased Risk ◽  
Antibody Levels ◽  
Chondroitin Sulfate A

ABSTRACTPlacental malaria, caused by sequestration ofPlasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity.

scholarly journals Efficacy of Two Alternate Vaccines Based on Plasmodium falciparum Merozoite Surface Protein 1 in anAotus Challenge Trial

2001 ◽  
Vol 69 (3) ◽  
pp. 1536-1546 ◽  
Author(s):  
Anthony W. Stowers ◽  
Vittoria Cioce ◽  
Richard L. Shimp ◽  
Mark Lawson ◽  
George Hui ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Vaccine Antigen ◽  
Merozoite Surface Protein 1 ◽  
Adjuvant Vaccine ◽  
New Formulation ◽  
Antibody Levels

ABSTRACT In an attempt to produce a more defined, clinical-grade version of a vaccine based on Plasmodium falciparum merozoite surface protein 1 (MSP1), we evaluated the efficacy of two recombinant forms of MSP1 in an Aotus nancymai challenge model system. One recombinant vaccine, bvMSP142, based on the 42-kDa C-terminal portion of MSP1, was expressed as a secreted protein in baculovirus-infected insect cells. A highly pure baculovirus product could be reproducibly expressed and purified at yields in excess of 8 mg of pure protein per liter of culture. This protein, when tested for efficacy in the Aotus challenge model, gave significant protection, with only one of seven monkeys requiring treatment for uncontrolled parasitemia after challenge with P. falciparum. The second recombinant protein, P30P2MSP119, has been used in previous studies and is based on the smaller, C-terminal 19-kDa portion of MSP1 expressed inSaccharomyces cerevisiae. Substantial changes were made in its production process to optimize expression. The optimum form of this vaccine antigen (as judged by in vitro and in vivo indicators) was then evaluated, along with bvMSP142, for efficacy in theA. nancymai system. The new formulation of P30P3MSP119 performed significantly worse than bvMSP142 and appeared to be less efficacious than we have found in the past, with four of seven monkeys in the vaccinated group requiring treatment for uncontrolled parasitemia. With both antigens, protection was seen only when high antibody levels were obtained by formulation of the vaccines in Freund's adjuvant. Vaccine formulation in an alternate adjuvant, MF59, resulted in significantly lower antibody titers and no protection.

scholarly journals Antibodies That Inhibit Plasmodium falciparum Adhesion to Chondroitin Sulfate A Are Associated with Increased Birth Weight and the Gestational Age of Newborns

2003 ◽  
Vol 71 (11) ◽  
pp. 6620-6623 ◽  
Author(s):  
Patrick E. Duffy ◽  
Michal Fried
Keyword(s):  
Plasmodium Falciparum ◽  
Birth Weight ◽  
Chondroitin Sulfate ◽  
Pregnancy Outcomes ◽  
Placental Malaria ◽  
Western Kenya ◽  
Antibody Levels ◽  
Pregnancy Malaria ◽  
Reduced Risk ◽  
Chondroitin Sulfate A

ABSTRACT Antibodies that inhibit Plasmodium falciparum adhesion to the placental receptor chondroitin sulfate A are associated with a reduced risk of placental malaria, but whether these antibodies lead to improved pregnancy outcomes is unknown. We measured antiadhesion antibody levels in parturient women in western Kenya, where malaria transmission is intense. Secundigravid women with antiadhesion activity in their plasma delivered babies that were on average 398 g heavier (P = 0.019) and 2 weeks more mature (P = 0.002) than babies delivered to secundigravidas without antiadhesion activity. Our findings support the development of antiadhesion vaccines to prevent poor fetal outcomes due to pregnancy malaria.

IgG subclass antibodies to three variants of Plasmodium falciparum merozoite surface protein-1 (PfMSP-119) in an area with unstable malaria transmission in Iran

Acta Tropica ◽  
2011 ◽  
Vol 119 (2-3) ◽  
pp. 84-90 ◽  
Author(s):  
Akram Abouie Mehrizi ◽  
Sara Asgharpour ◽  
Ali-Hatef Salmanian ◽  
Navid Dinparast Djadid ◽  
Sedigheh Zakeri
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Igg Subclass ◽  
Merozoite Surface Protein 1 ◽  
Falciparum Merozoite

scholarly journals Extensive Antigenic Polymorphism within the Repeat Sequence of the Plasmodium falciparum Merozoite Surface Protein 1 Block 2 Is Incorporated in a Minimal Polyvalent Immunogen

2005 ◽  
Vol 73 (9) ◽  
pp. 5928-5935 ◽  
Author(s):  
Kevin K. A. Tetteh ◽  
David R. Cavanagh ◽  
Patrick Corran ◽  
Rosemary Musonda ◽  
Jana S. McBride ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Single Molecule ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Repeat Sequence ◽  
Allelic Polymorphism ◽  
Length Variation ◽  
Candidate Sequence ◽  
Merozoite Surface Protein 1 ◽  
Allelic Sequence

ABSTRACT Polymorphism in pathogen antigens presents a complex challenge for vaccine design. A prime example is the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP1), to which allele-specific antibodies have been associated with protection from malaria. In a Zambian population studied here, 49 of 91 alleles sampled were of the K1-like type (the most common of three block 2 types in all African populations), and most of these had unique sequences due to variation in tri- and hexapeptide repetitive motifs. There were significant negative correlations between allelic sequence lengths of different regions of the repeats, so the complete repeat sequence had less length variation than its component parts, suggesting a constraint on overall length. Diverse epitopes recognized by three murine monoclonal antibodies and 24 individual human sera were then mapped by using a comprehensive panel of synthetic peptides, revealing epitopes in all regions of the repeats. To incorporate these different epitopes in a single molecule, a composite sequence of minimal overall length (78 amino acids) was then designed and expressed as a recombinant antigen. More human immune sera reacted with this “K1-like Super Repeat” antigen than with proteins consisting of single natural allelic sequences, and immunization of mice elicited antibodies that recognized a range of five cultured parasite lines with diverse K1-like MSP1 block 2 repeat sequences. Thus, complex allelic polymorphism was deconstructed and a minimal composite polyvalent antigen was engineered, delivering a designed candidate sequence for inclusion in a malaria vaccine.

Selection and genetic drift of polymorphisms within the merozoite surface protein-1 gene of Plasmodium falciparum

Gene ◽  
2000 ◽  
Vol 241 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Kazuyuki Tanabe ◽  
Naoko Sakihama ◽  
Yoshimitu Nakamura ◽  
Osamu Kaneko ◽  
Masatugu Kimura ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Drift ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Merozoite Surface Protein 1
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