Characterization of the effector mechanisms of a transmission-blocking antibody upon differentiation ofPlasmodium bergheigametocytes into ookinetesin vitro

Parasitology ◽  
1994 ◽  
Vol 109 (1) ◽  
pp. 11-17 ◽  
Author(s):  
G. R. R. Ranawaka ◽  
A. R. Alejo-Blanco ◽  
R. E. Sinden
Keyword(s):  
Mechanisms Of Action ◽  
Antibody Activity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Maximal Inhibition ◽  
Blocking Antibody ◽  
Transmission Blocking ◽  
Ammonium Sulphate Precipitation ◽  
Papain Digestion ◽  
Peripheral Blood Leucocytes

SUMMARYThe transmission-blocking monoclonal antibody 13.1, which recognizes the ookinete surface antigen Pbs21 ofPlasmodium berghei, and an IgG2a isotype control antibody 26.37 were purified by caprylic acid and ammonium sulphate precipitation. Fab fragments were prepared by papain digestion. IgG but not Fab from antibody 13.1 reduced ookinete formation byP. bergheiin culture by as much as 94% at a concentration of 100 μg/ml. There was little difference in antibody efficacy in the range 6·25–400 μg/ml in this assay. The parasite was most sensitive to antibody activity in the first 6–9 h of culture, i.e. the gamete/zygote and early retort stages. Peripheral blood leucocytes (PBL) were essential to achieve maximal inhibition by mAb 13.1 (activity was abrogated totally if PBL were removed). Together the data suggest that one of the mechanisms of action of this antibody is antibody-mediated PBL killing. Phagocytosis of parasites was noted in these experiments in all cultures. We have not attempted in this study to distinguish between Fc-mediated opsonization, as opposed to antibody-dependent cellular cytotoxicity.

scholarly journals Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Brandon McLeod ◽  
Kazutoyo Miura ◽  
Stephen W. Scally ◽  
Alexandre Bosch ◽  
Ngan Nguyen ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Affinity Maturation ◽  
Human Antibody ◽  
Blocking Antibody ◽  
Transmission Blocking ◽  
Clinical Models ◽  
Humoral Responses ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

Abstract Transmission-blocking vaccines have the potential to be key contributors to malaria elimination. Such vaccines elicit antibodies that inhibit parasites during their development in Anopheles mosquitoes, thus breaking the cycle of transmission. To date, characterization of humoral responses to Plasmodium falciparum transmission-blocking vaccine candidate Pfs25 has largely been conducted in pre-clinical models. Here, we present molecular analyses of human antibody responses generated in a clinical trial evaluating Pfs25 vaccination. From a collection of monoclonal antibodies with transmission-blocking activity, we identify the most potent transmission-blocking antibody yet described against Pfs25; 2544. The interactions of 2544 and three other antibodies with Pfs25 are analyzed by crystallography to understand structural requirements for elicitation of human transmission-blocking responses. Our analyses provide insights into Pfs25 immunogenicity and epitope potency, and detail an affinity maturation pathway for a potent transmission-blocking antibody in humans. Our findings can be employed to guide the design of improved malaria transmission-blocking vaccines.

scholarly journals In Vitro Characterization of the Antibacterial Spectrum of Novel Bacterial Type II Topoisomerase Inhibitors of the Aminobenzimidazole Class

2006 ◽  
Vol 50 (4) ◽  
pp. 1228-1237 ◽  
Author(s):  
Nagraj Mani ◽  
Christian H. Gross ◽  
Jonathan D. Parsons ◽  
Brian Hanzelka ◽  
Ute Müh ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Wide Spectrum ◽  
Dna Gyrase ◽  
Antibacterial Activities ◽  
Mechanisms Of Action ◽  
Fluoroquinolone Resistance ◽  
Topoisomerase Iv ◽  
Low Frequencies

ABSTRACT Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities.

Monoclonal Antibodies against the Tn-Specific Isolectin B4 fromVicia villosaSeeds: Characterization of the Epitope of the Blocking Antibody VV34

2004 ◽  
Vol 23 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Andrea Medeiros ◽  
Nora Berois ◽  
Henia Balter ◽  
Ana Robles ◽  
Enrique Perez-Payá ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Blocking Antibody ◽  
Isolectin B4

scholarly journals Membrane glycopeptides from old and young human erythrocytes (Short Communication)

1974 ◽  
Vol 140 (3) ◽  
pp. 557-560 ◽  
Author(s):  
Cesare Balduini ◽  
Carlo Luigi Balduini ◽  
Edoardo Ascari
Keyword(s):  
Sialic Acid ◽  
Erythrocyte Membrane ◽  
Human Erythrocyte ◽  
Short Communication ◽  
Chemical Characterization ◽  
Erythrocyte Membranes ◽  
Main Peak ◽  
Human Erythrocyte Membranes ◽  
Papain Digestion

Glycopeptides were extracted by papain digestion from old and young human erythrocyte membranes and fractionated on DEAE-Sephadex A-25. Chemical characterization of the unfractionated samples and of the main peak eluted from the column indicates that glycoproteins of the erythrocyte membrane undergo significant decreases in sialic acid and galactosamine content with aging.

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