Duffy blood group and its relationship to malaria vaccine

Duffy Blood Group System and the malaria adaptation process in humans

duffy blood group and its relationship to malaria vaccine

This has influenced the variation in Duffy blood types seen in populations where malaria is common. It also binds the malaria parasite Plasmodium vivax, and RBCs that lack the Duffy Fya and Fyb . The Duffy antigens known to have caused maternal immunization and subsequent hemolytic . Related information . OMIM. Duffy antigen/chemokine receptor (DARC), also known as Fy glycoprotein (FY) or CD (Cluster of Differentiation ), is a protein that in humans is encoded by the DARC gene. The Duffy antigen is located on the surface of red blood cells, and is named .. The association between the Duffy antigen and HIV infection appears to be. Thus, the Duffy blood group of vaccines against malaria, but little.

This suggests that the relative frequencies of Fya and Fyb alleles in these populations may affect DBP vaccine efficacy. Alternatively, DBP might remain the critical invasion ligand using alternate receptors for invasion.

This novel ligand is anticipated to be involved in an alternate invasion pathway to DBP. Several in vitro assays have been used to study the interaction between the ligand domains of P.

The region between cysteines 4 and 7 constitutes the major determinants for receptor recognition. This mechanism of interaction suggests that dimerization is critical for, and driven by DARC binding, leading to the formation of a stable high-affinity complex composed of two DBP and two DARC molecules.

Unlike the parasite ligands, ECD1 alone is not sufficient for chemokine binding. A schematic for the stepwise assembly is shown at the bottom.

Red blood cell invasion by Plasmodium vivax: Current opinion and future therapeutic prospects Chemokines and their receptors play a major role in facilitating the entry and transmission of intracellular pathogens, typical examples being in HIV and P.

Duffy blood group and malaria.

As such, they represent attractive targets for novel therapeutics. Methods that can prevent receptor—ligand interaction such as interfering with signaling pathways that are induced upon receptor activation and modification of receptor trafficking pathways can be explored to develop therapeutics. This is mainly based on the evidence that some individuals are able to develop long-lasting and strain-transcending inhibitory antibodies against DBPII.

Notwithstanding, strategies targeting the other counterpart of this host—parasite interaction in the blood stream, that is DARC, have not been intensively explored.

To date, it is mostly established that P.

duffy blood group and its relationship to malaria vaccine

Inhibition of this key interaction provides an excellent opportunity for parasite inhibition. This shows the importance of the DARC binding pocket and dimer formation for parasite survival. These molecules if targeted to the dimer interface and receptor-binding pocket, they could prevent dimer formation and consequently merozoite invasion. Vaccines as a therapeutic tool Vaccines are considered the best means of control of infectious diseases.

Over 70 different vaccines against P. The most promising vaccine against P. Unfortunately, the same advances have not been seen for vaccines against P.

Duffy blood group and malaria.

A series of P. These include the apical membrane antigen AMA-198 DBP, 99reticulocyte binding proteins,and merozoite surface proteins. Because of the difficulty in obtaining enough reticulocytes, long-term culture for P. Despite these challenges, a number of potential strategies are being explored for the development of a P.

Some studies have reported strategies to overcoming strain-specific immunity in P. Notwithstanding, the efficacy of a DBP-based vaccine may differ among populations with varying Fy phenotypes. Several chemokine receptors have been validated as successful targets of anti-inflammatory therapies and anti-HIV infectivity strategy. A new biotechnology tool for genome editing, CRISPR, has gained wide interest in the scientific world and researchers believe that it could transform the field of biology.

An example is engineered monkeys with targeted mutations to prevent HIV infections in human cells.

  • Duffy Blood Group System and the malaria adaptation process in humans.
  • Duffy antigen system

An alternate DARC-related approach to vaccines is the use of novel agents specific for individual malaria species targeting their pathways of invasion. Zinc finger array precursors of zinc finger nucleases, which are artificial hybrid restriction enzymes, are becoming powerful tools for primary editing of host genomes as a strategy to halt pathogen infectivity. The feasibility of this approach is supported by existing evidence pointing to resistance of RBCs of naturally selected Duffy-negative blacks to P.

Duffy Blood Group System and the malaria adaptation process in humans

Small molecule agonists and antagonists as inhibitors of receptor-ligand interaction The interaction between chemokine receptors and their ligands involves initial interaction with the N-terminal extracellular domains of the receptor, generally mediated by electrostatic forces. Modifications of these regions, using chemokine analogues, either truncations or extension of the amino terminus, — have been found to retain affinity for the receptors, while impairing signaling.

Chemokine receptor antagonists are still in early stages of development. Through screening of small molecules, Pfizer was able to identify a small molecule inhibitor that could block the gp binding to the chemokine receptor CCR5. The disease is transmitted through the bite of female Anopheles mosquitoes, even though in certain situations other mechanisms are possible.

Additionally they are receptors for the chemokine family involved in the regulation of inflammatory processes. This resistance appears to have significantly influenced the distribution of Duffy system phenotypes in areas where malaria is endemic. The etiologic agent, Plasmodium sp.

Malaria is caused by infestation of different species of protozoa of the genus Plasmodium: Mortality was also reduced from 3 deaths per 10, cases in to 1.

11. AB blood type (genetics)

In this same period, there was a considerable change in the transmission dynamics of malaria with concentrations of cases in specific municipalities. The number of municipalities at high risk, i. Sporadic autochthonic cases occurred in restricted focal areas.

duffy blood group and its relationship to malaria vaccine

Often, infant mortality and morbidity are related to delay in establishing the correct diagnosis because of few clinical features. This promotes the fertilization process producing zygotes that become invasive and grow and divide thus producing thousands of invasive sporozoites.

These migrate through the body and invade the salivary glands of female mosquitoes. Females, when they feed again, inoculate sporozoites in the blood of man, which rapidly migrate into hepatocytes and transform into trophozoites in the liver where they mature and divide to form thousands of merozoites.

The liver cells rupture releasing merozoites into the circulation, thereby initiating the blood cycle. In this phase, symptoms do not appear in the host.

Duffy Blood Group System and the malaria adaptation process in humans.

In the blood cycle, the merozoites develop into trophozoites forming schizonts. This stage of the cycle is associated with clinical symptoms. After a period of asexual replication, some merozoites differentiate into gametocytes and become infective to mosquitoes.