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- Table of Contents
Facts about D site-binding protein.
May be a direct target for regulation by the circadian pacemaker element clock. May affect circadian period and sleep regulation.
Human | |
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Gene Name: | DBP |
Uniprot: | Q10586 |
Entrez: | 1628 |
Belongs to: |
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bZIP family |
Albumin D box-binding protein; Albumin D-element-binding protein; D site of albumin promoter (albumin D-box) binding protein; D site-binding protein; DABP; taxREB302; Tax-responsive enhancer element-binding protein 302
Mass (kDA):
34.349 kDA
Human | |
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Location: | 19q13.33 |
Sequence: | 19; NC_000019.10 (48630030..48637379, complement) |
Ubiquitously expressed. Expressed in the suprachiasmatic nuclei (SCN) and in most peripheral tissues, with a strong circadian rhythmicity.
Nucleus.
This article will focus on the primary vaccine targets in PvDBP. This protein induces antibodies that are both sexual and asexual against the parasite. These antibodies will hopefully one day be used in the fight against malaria and the parasite. We must continue to develop vaccines against the parasite in order to end it. Read on to find out more about the best uses that this marker has in boster biology.
Plasmodium VIVAX PvDBP is a promising candidate for a malaria vaccine. However, the parasite is polymorphic so it induces specific immune responses. Further, there is currently no consensus on the epitopes of broadly neutralizing antibodies to PvDBP, which hinders rational design of potent DBP-based vaccines. It is important to identify globally conserved Epitopes. The DBP epitopes can be identified and used as potential vaccine candidates by performing mutational mapping.
The circumsporozoite proteins (CSP), is a key target in malaria vaccine development. This protein is made up of T cell epitopes. Yeast containing "S" expression cassettes can be used to express RTS and S. It also contains the P. falciparum-CSP fragment. Yeast expresses this polypeptide, which is then spontaneously assembles into mixed lipoprotein particles.
PvCSP vaccine demonstrated a delayed latent period in the phase I/I studies. Single-stage antigens cannot cause sterile protection. Instead, multiple targets should have been used in the next-generation P.vivax vaccine. This strategy has been successful in P. Falciparum vaccine development. The use of multiple targets has been shown increase the effectiveness of vaccines.
TLR4 agonists found in PvCSP induce cytophilic T cell responses in vitro, and induce IL-2 and TNF release from CD4+ cells. In addition, the PvCSP recombinant vaccine induces protection by activating B cells and macrophages. The PvCSP vaccine induces TNF production and a reduction in IL-2 levels in human immune cells.
The 42-kDa segment of MSP-1 protein was also targeted by the researchers. This potential vaccine candidate was also investigated. They observed that the recombinant proteins induced a strong immune response among BALB/c animals. The recombinant PvCSP c chimera was able to produce antibodies that agglutinate the Spz. This indicates the Spz's infective capacity has been lost. While both rPvCSP-c and VMP 001 are immunogenic, rPvCSP-c also has high antibody specificity against variants of PvCSP.
Boster Bio is not only focusing on the antigens but also the microbial vectors which infect rodents as well as primates. Because it plays multiple roles in disease transmission, the PvDBP is an important target for malaria prevention. It is crucial that the vaccine candidate has a wide immune spectrum and is safe for humans. The safety of the candidate vaccination is being evaluated by the company. It is too early to draw definitive conclusions. However the development process is moving forward and there is a lot to come.
It also offers stability benefits. Plant-based rPA has allowed the company to achieve increased stability in a powder spray-dried formulation. This eliminates the need to use cold chains and gives the company greater confidence in its ability to stockpile the vaccine for civilian or military use. The company is confident it can produce a vaccine candidate against SARS in a matter of years.
Recent results from a study have shown that Boster Bio’s PvDBP can trigger T cell responses to fight malaria. In both groups, the MVA PvDBP elicits significantly more T-cell responses than placebo. We used the KruskalWallis test as well as Dunn's multiple comparison to verify this claim.
Boster Bio PvDBP RII induces antibodies against parasite asexuality according to binding assay. The recombinant proteins bound to reticulocytes in a concentration-dependent manner. As negative and positive controls, PvRBP, GST-His, neuraminidase, and PvRBP-2 were used. The recombinant proteins bound to the reticulocytes at a concentration of 20mg/ml in a dose-dependent fashion.
After two weeks of treatment, serum antibody responses showed decreased levels, but were still higher than preboost levels. The results showed that there were no significant differences in serum antibodies between the different groups. This suggests that the vaccine induces antibodies against parasite asexual phases. This is a promising result for a vaccine against Malaria. Boster Bio's PvDBP induces anti-parasite antibodies, as demonstrated by the results.
Results from a previous study indicated that PvDBP RII induced IL-10 and IFN-g T cell responses. These responses were age dependent. The six peptide pool vaccines induced IFN–g T cell responses that were widely distributed across all six pools. The peptide mapping of the PvDBP-RII immunogen revealed that three epitopes contained polymorphic residues, which triggered variant-specific cellular responses.
The HMP013 Indian P.vivax strain has been frozen for use in CHMI clinical trial. The HMP013 PvDBP -RII has a binding-inhibition titer of 50% that is similar to the Oxford assay. In the Oxford assay, both the SalI variants had similar binding inhibition titers.
We used the PvRBP1a-PvRBP1b PvRBP1b protein recombinant proteins in the current study to induce antibodies towards the parasite's asexual stage. Two-step procedures were used to determine whether the PvRBPs inducing antibodies were effective. First, rabbit immune sera had to be double-labeled in two steps with anti-MSP1a and anti-PvDBP RII immuno-reactive antibodies. Finally, immunohistochemical staining was performed with DAPI.
The RRBP family is a highly immunogenic group of proteins that mediate the invasion process of parasites. Both PvRBP1a and PvRBP2a are essential ligands for the parasites. The RRBP family members have a common N-terminal structure and structural conservation.
Induced responses of T cells to ChAd63 could be used to induce antibody responses against malaria. This platform was originally created to induce T cell reactions against the blood stage antibody in humans. The vaccine was also tested in mice. PvDBP/RII induces IFNg T cell responses with median levels 2,000 SFU/million in PBMCs.
Boster Bio’s PvDBP induces immune responses similar to natural infection in endemic population. The vaccine induces antibodies that are mainly composed of IgG1-IgG3 proteins. They also exhibit moderate avidity. The exact proportion of each antibody isotype as well as its affinity and avidity are not known, but they are consistent for endemic malaria infection.
The immunological response to PVX_081550, a vaccine candidate from Boster Bio, was observed in endemic areas of P. vivax. It was lower that the MSP119 subclass, however it increased more than 100-fold for individuals with at least three episodes. The antigens were the PVX_081550, GAMA, P12, P41, CSP, RBP1a and RBP2cNB, as well as the reticulocyte-specific protein (CSP).
The peptides present in Boster Bio's PvDBP have high affinity for reticulocytes. These peptides are easily recognized in patient sera as well as immunized mice. These experiments resulted in cytophilic antibodies that induced cell-mediated inhibition and antibody-dependent inhibition of the parasite’s growth. The antigens in these experiments were immunogenic and induced Th2/Th2 immune responses.
Boster Bio's PvDBP is a highly immunogenic peptide that induces antibodies against the parasite's male and female stages. Although the peptide causes an IgG response in rhesus monkeys, this is not due cross-reactivity. Boster Bio's PvDBP has an antigenicity that is indicative of its potential effectiveness.
Boster Bio's PvCSP contains a TLR agonist to improve the immune response. The vaccine produced antibodies against Aotus Nancymaae's C-terminal region and the VK210 repeat region. After the experimental challenge, 66.7% were protected against the parasite. The activation and inhibition of MMP-1 activities also promoted activation in B-cells.
The study also revealed that a significant number of volunteers had extremely high IgG levels against CSP and RBP proteins. The results of the study, although not directly comparable to the others, are promising and suggest that this drug can be used to instill vaccines against malaria. The research is published in the journal PLoS Negl Trop Dis (10.13758)
The study also examined the effects of demographic and epidemiological factors on antibody response. The results of this study show that Boster Bio's PvDBP can induce antibodies to the parasite's sexual stages. However, a previous study found that RBP1a has a protective effect against clinical Malaria. It is important not to forget that RBP1a increases the immune response in children.
PvDBP (pronounced "polymorphic") is a P. vivax-derived protein. It is composed of a highly polymorphic central region. It also has C terminal domains which are highly conserved. During the erythocyte cycle, PvMSP3 interacts with the Mrz-surface. If the immune response is stronger to P.vivax, this could indicate a vaccine.
PMID: 7835883 by Khatib Z.A., et al. Chromosomal localization and cDNA cloning of the human DBP and TEF genes.
PMID: 8786133 by Shutler G., et al. Genomic structure of the human D-site binding protein (DBP) gene.