scholarly journals Measurement of Antibody Levels against Region II of the Erythrocyte-Binding Antigen 175 of Plasmodium falciparum in an Area of Malaria Holoendemicity in Western Kenya

2004 ◽  
Vol 72 (2) ◽  
pp. 735-741 ◽  
Author(s):  
Eunita A. Ohas ◽  
John H. Adams ◽  
John N. Waitumbi ◽  
Alloys S. S. Orago ◽  
Arnoldo Barbosa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Sialic Acid ◽  
Inhibitory Activity ◽  
Western Kenya ◽  
Transmission Season ◽  
High Transmission ◽  
Exposed Population ◽  
Erythrocyte Binding ◽  
Antibody Levels ◽  
Region Ii

ABSTRACT Region II of the 175-kDa erythrocyte-binding antigen (EBA-175RII) of Plasmodium falciparum is functionally important in sialic acid-dependent erythrocyte invasion and is considered a prime target for an invasion-blocking vaccine. The objectives of this study were to (i) determine the prevalence of anti-EBA-175RII antibodies in a naturally exposed population, (ii) determine whether naturally acquired antibodies have a functional role by inhibiting binding of EBA-175RII to erythrocytes, and (iii) determine whether antibodies against EBA-175RII correlate with immunity to clinical malaria. We treated 301 lifelong residents of an area of malaria holoendemicity in western Kenya for malaria, monitored them during a high-transmission season, and identified 33 individuals who were asymptomatic despite parasitemia (clinically immune). We also identified 50 clinically susceptible individuals to serve as controls. These 83 individuals were treated and monitored again during the subsequent low-transmission season. Anti-EBA-175RII antibodies were present in 98.7% of the individuals studied. The antibody levels were relatively stable between the beginning and end of the high-transmission season and correlated with the plasma EBA-175RII erythrocyte-binding-inhibitory activity. There was no difference in anti-EBA-175RII levels or plasma EBA-175RII erythrocyte-binding-inhibitory activity between clinically immune and clinically susceptible groups. However, these parameters were higher in nonparasitemic than in parasitemic individuals at enrollment. These results suggest that although antibodies against EBA-175RII may be effective in suppressing some of the wild parasite strains, EBA-175RII is unlikely to be effective as a monovalent vaccine against malaria, perhaps due to allelic heterogeneity and/or presence of sialic acid-independent strains.

scholarly journals Genotyping cognate Plasmodium falciparum in humans and mosquitoes to estimate onward transmission of asymptomatic infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kelsey M. Sumner ◽  
Elizabeth Freedman ◽  
Lucy Abel ◽  
Andrew Obala ◽  
Brian W. Pence ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Odds Ratio ◽  
Asymptomatic Malaria ◽  
Major Contributor ◽  
Western Kenya ◽  
High Transmission ◽  
Transmission Reduction ◽  
Asymptomatic Infections ◽  
Infection Types ◽  
Natural Settings

AbstractMalaria control may be enhanced by targeting reservoirs of Plasmodium falciparum transmission. One putative reservoir is asymptomatic malaria infections and the scale of their contribution to transmission in natural settings is not known. We assess the contribution of asymptomatic malaria to onward transmission using a 14-month longitudinal cohort of 239 participants in a high transmission site in Western Kenya. We identify P. falciparum in asymptomatically- and symptomatically-infected participants and naturally-fed mosquitoes from their households, genotype all parasites using deep sequencing of the parasite genes pfama1 and pfcsp, and use haplotypes to infer participant-to-mosquito transmission through a probabilistic model. In 1,242 infections (1,039 in people and 203 in mosquitoes), we observe 229 (pfcsp) and 348 (pfama1) unique parasite haplotypes. Using these to link human and mosquito infections, compared with symptomatic infections, asymptomatic infections more than double the odds of transmission to a mosquito among people with both infection types (Odds Ratio: 2.56; 95% Confidence Interval (CI): 1.36–4.81) and among all participants (OR 2.66; 95% CI: 2.05–3.47). Overall, 94.6% (95% CI: 93.1–95.8%) of mosquito infections likely resulted from asymptomatic infections. In high transmission areas, asymptomatic infections are the major contributor to mosquito infections and may be targeted as a component of transmission reduction.

scholarly journals Moderately Neutralizing Epitopes in Nonfunctional Regions Dominate the Antibody Response toPlasmodium falciparumEBA-140

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Nichole D. Salinas ◽  
May M. Paing ◽  
Jagat Adhikari ◽  
Michael L. Gross ◽  
Niraj Tolia
Keyword(s):  
Immune Response ◽  
Sialic Acid ◽  
Neutralizing Antibodies ◽  
Fold Increase ◽  
Binding Pocket ◽  
Content Type ◽  
Tight Junction Formation ◽  
Sialic Acid Binding ◽  
Erythrocyte Binding ◽  
Region Ii

ABSTRACTPlasmodium falciparumerythrocyte-binding antigen 140 (EBA-140) plays a role in tight junction formation during parasite invasion of red blood cells and is a potential vaccine candidate for malaria. Individuals in areas where malaria is endemic possess EBA-140-specific antibodies, and individuals with high antibody titers to this protein have a lower rate of reinfection by parasites. The red blood cell binding segment of EBA-140 is comprised of two Duffy-binding-like domains, called F1 and F2, that together create region II. The sialic acid-binding pocket of F1 is essential for binding, whereas the sialic acid-binding pocket in F2 appears dispensable. Here, we show that immunization of mice with the complete region II results in poorly neutralizing antibodies. In contrast, immunization of mice with the functionally relevant F1 domain of region II results in antibodies that confer a 2-fold increase in parasite neutralization compared to that of the F2 domain. Epitope mapping of diverse F1 and F2 monoclonal antibodies revealed that the functionally relevant F1 sialic acid-binding pocket is a privileged site inaccessible to antibodies, that the F2 sialic acid-binding pocket contains a nonneutralizing epitope, and that two additional epitopes reside in F1 on the opposite face from the sialic acid-binding pocket. These studies indicate that focusing the immune response to the functionally important F1 sialic acid binding pocket improves the protective immune response of EBA-140. These results have implications for improving future vaccine designs and emphasize the importance of structural vaccinology for malaria.

scholarly journals Lack of Association between Maternal Antibody and Protection of African Infants from Malaria Infection

2000 ◽  
Vol 68 (10) ◽  
pp. 5856-5863 ◽  
Author(s):  
E. M. Riley ◽  
G. E. Wagner ◽  
M. F. Ofori ◽  
J. G. Wheeler ◽  
B. D. Akanmori ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Direct Evidence ◽  
Protective Role ◽  
Transmission Season ◽  
Time Of Infection ◽  
Antigen Antibody ◽  
Antibody Levels ◽  
Southern Ghana

ABSTRACT Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparumschizonts and recombinant circumsporozoite antigen, MSP-119, MSP-2, AMA-1, and Pf155 (also called ring-infected erytrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/μl of blood) were seronegative for MSP-119 at the time of infection.

scholarly journals Safety and Immunogenicity of a Recombinant Nonglycosylated Erythrocyte Binding Antigen 175 Region II Malaria Vaccine in Healthy Adults Living in an Area Where Malaria Is Not Endemic

2010 ◽  
Vol 17 (10) ◽  
pp. 1552-1559 ◽  
Author(s):  
H. M. El Sahly ◽  
S. M. Patel ◽  
R. L. Atmar ◽  
T. A. Lanford ◽  
T. Dube ◽  
...  
Keyword(s):  
United States ◽  
Malaria Vaccine ◽  
Aluminum Phosphate ◽  
The United States ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Reactions ◽  
Erythrocyte Binding ◽  
Low Levels ◽  
Antibody Levels ◽  
Region Ii

ABSTRACT Erythrocyte binding antigen region II (EBA-175) is a conserved antigen of Plasmodium falciparum that is involved in binding of the parasite to the host's erythrocytes. We evaluated the safety and immunogenicity of a recombinant EBA-175 vaccine with aluminum phosphate adjuvant in healthy young adults living in the United States. Eighteen subjects/group received ascending doses (5, 20, 80, or 160 μg) of the vaccine at 0, 1, and 6 months; 8 subjects received placebo. Most of the injection site and systemic reactions were mild to moderate in intensity. After 2 or 3 doses of the vaccine at any concentration, antibody levels measured by enzyme-linked immunosorbent assay were significantly higher than those for the placebo group. Sera from subjects who received 3 doses of the vaccine at any concentration inhibited the growth of erythrocyte-stage P. falciparum at low levels compared to sera from placebo recipients or preimmune sera. In conclusion, the EBA-175 vaccine with adjuvant was safe and immunogenic in malaria-naïve subjects.

scholarly journals Invasion Profiles of Brazilian Field Isolates of Plasmodium falciparum: Phenotypic and Genotypic Analyses

2004 ◽  
Vol 72 (10) ◽  
pp. 5886-5891 ◽  
Author(s):  
Cheryl-Ann Lobo ◽  
Karla de Frazao ◽  
Marilis Rodriguez ◽  
Marion Reid ◽  
Mariano Zalis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Invasion Pathways ◽  
Parasite Invasion ◽  
Specific Amino Acid ◽  
Field Isolates ◽  
Erythrocyte Invasion ◽  
Erythrocyte Binding ◽  
Normal Enzyme ◽  
Region Ii ◽  
Distinct Field

ABSTRACT The invasion of red blood cells (RBCs) by Plasmodium falciparum is dependent on multiple molecular interactions between erythrocyte receptors and parasite ligands. Invasion studies using culture-adapted parasite strains have indicated significant receptor heterogeneity. It is not known whether this heterogeneity reflects the parasite invasion arsenal in the field. We have studied the invasion phenotypes of 14 distinct field isolates from the Legal Amazon areas of Brazil by using erythrocyte invasion assays to investigate invasion into normal, enzyme-treated, and clinical-mutant RBCs. Analysis of these isolates revealed four distinct invasion profiles. Using En(a−) cells to get an unequivocal estimate of the use of glycophorin A (GPA) as a receptor, we found that the 175-kDa erythrocyte-binding antigen (EBA-175)/GPA pathway was used by a minority of the parasite isolates studied. Although polymorphism of region II domains at specific amino acid positions in both EBA-140 and EBA-181 was found in these field isolates, this did not correlate with invasion profiles and thus receptor selectivity. These studies have further confirmed the existence of a significant diversity of invasion pathways in nature and suggest that additional parasite ligands will have to be targeted to devise global vaccines that will work in the field.

scholarly journals Comparison of non-magnetic and magnetic beads multiplex assay for assessment of Plasmodium falciparum antibodies

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6120 ◽  
Author(s):  
Bartholomew N. Ondigo ◽  
Gregory S. Park ◽  
Cyrus Ayieko ◽  
Donald D. Nyangahu ◽  
Ronald Wasswa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Magnetic Beads ◽  
Negative Control ◽  
Suitable Alternative ◽  
Western Kenya ◽  
Multiplex Assays ◽  
Immune Parameters ◽  
Antibody Assays ◽  
Antibody Levels ◽  
Control Plasma

Background New reagents have emerged allowing researchers to assess a growing number of vaccine-associated immune parameters. Multiplex immunoassay(s) are emerging as efficient high-throughput assays in malaria serology. Currently, commercial vendors market several bead reagents for cytometric bead assays (CBA) but relative performances are not well published. We have compared two types of bead-based multiplex assays to measure relative antibody levels to malarial antigens. Methods Assays for the measurement of antibodies to five Plasmodium falciparum vaccine candidates using non-magnetic and magnetic fluorescent microspheres were compared for their performances with a Bio-Plex200 instrument. Mean fluorescence intensity (MFI) was determined from individuals from western Kenya and compared to known positive and negative control plasma samples. Results P. falciparum recombinant antigens were successfully coupled to both non-magnetic and magnetic beads in multiplex assays. MFIs between the two bead types were comparable for all antigens tested. Bead recovery was superior with magnetic beads for all antigens. MFI values of stored non-magnetic coupled beads did not differ from freshly coupled beads, though they showed higher levels of bead aggregation. Discussion Magnetic and non-magnetic beads performed similarly in P. falciparum antibody assays. Magnetic beads were more expensive, but had higher bead recovery, were more convenient to use, and provided rapid and easy protocol manipulation. Magnetic beads are a suitable alternative to non-magnetic beads in malarial antibody serology.

scholarly journals Evidence for two-stage binding by the 175-kD erythrocyte binding antigen of Plasmodium falciparum.

1993 ◽  
Vol 178 (5) ◽  
pp. 1497-1505 ◽  
Author(s):  
K C Kain ◽  
P A Orlandi ◽  
J D Haynes ◽  
K L Sim ◽  
D E Lanar
Keyword(s):  
Plasmodium Falciparum ◽  
Sialic Acid ◽  
Conformational Changes ◽  
Plasmodium Falciparum Malaria ◽  
Multistage Process ◽  
Cellular Receptors ◽  
Homologous Part ◽  
Erythrocyte Binding ◽  
Initial Interaction ◽  
Endogenous Proteases

Plasmodium falciparum malaria merozoites invade human erythrocytes bearing sialic acid in a multistage process involving the sialic acid-dependent binding of a malaria molecule, the 175-kD erythrocyte binding antigen (EBA-175). We show here that after the initial interaction of EBA-175 with its sialic acid-containing erythrocyte determinant, endogenous proteases can cleave EBA-175 to 65-kD fragment(s), whose binding to erythrocytes is sialic acid independent. A 65-kD fragment was immunoprecipitated by antibodies against peptides between residues 354 and 1061 but not beyond residue 1062. Binding experiments utilizing combinations of native protein, expression-PCR-synthesized EBA-175 polypeptides, peptide synthesis, and antibodies, demonstrated that sialic acid-independent binding could be further mapped to a small (about 40-amino acid) homologous part of the dimorphic allelic region of EBA-175, residues 898-938 (Camp strain numbering). These data support a two-step binding hypothesis and are discussed in relation to the formation of a junction between the merozoite and the erythrocyte, and the finding that after the interaction of some viruses with specific cellular receptors, they undergo conformational changes or cleavage permitting membrane fusion with the host cell.

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