Dengue Envelope-1 & 3
Description
Dengue Envelope-1 (DENV-1 E)
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Expression: Recombinant DENV-1 DIII (D1ED III) is expressed in Escherichia coli and forms a ~11.3 kDa protein with >95% purity .
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Key Epitopes: Residues T329 in DIII are critical for monoclonal antibody (e.g., E106) binding and neutralization .
Dengue Envelope-3 (DENV-3 E)
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Expression: Produced in HEK293 cells as a glycosylated, soluble domain (amino acids 279–677) with a C-terminal His-tag, achieving >95% purity .
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Cross-Reactivity: Shares antigenic similarities with other flaviviruses (e.g., Zika, West Nile), complicating serological specificity .
IgM Detection in Acute Dengue
| Antigen Used | Sensitivity (%) | Specificity (%) |
|---|---|---|
| DENV-1 rED III alone | 59.09 | 100 |
| DENV-3 rED III alone | 45.45 | 100 |
| Combined (DENV-1/3/4) | 81.82 | 100 |
Combining DENV-1 and DENV-3 rED III antigens significantly improves IgM detection sensitivity in early infection (2–3 days post-symptom onset) by compensating for serotype-specific variations .
Role in Viral Entry Inhibition
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DENV-1 DIII: Blocks dengue-1 virus infection in BHK-21 cells by competitively binding cellular receptors, achieving >80% inhibition at 0.15 mg/mL .
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DENV-3 DIII: While not directly tested in the provided studies, its structural similarity to DENV-1 suggests analogous receptor-binding functionality .
Adjuvant Formulations for DENV-1 DIII
| Adjuvant | Neutralizing Antibody Response (FRNT₅₀) |
|---|---|
| PELC + CpG | 2⁴·⁶ |
| Aluminum phosphate | <2³ |
| CpG alone | <2³ |
The PELC (polyethylene glycol-block-poly(lactide-co-ε-caprolactone)) + CpG adjuvant enhances DENV-1 DIII-specific neutralizing antibodies, demonstrating durability up to 24 weeks post-immunization .
Challenges and Innovations
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Cross-Reactivity: DENV-1 and DENV-3 E proteins share epitopes with other flaviviruses (e.g., residues 386–397 in DENV-2 DIII), necessitating domain-specific diagnostics .
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Conformational Sensitivity: Proper folding of recombinant DIII is critical for inducing protective antibodies, as seen in HEK293-expressed DENV-3 E protein .
Future Directions
Product Specs
Product Science Overview
Dengue virus (DENV) is a mosquito-borne virus that causes dengue fever, a significant public health concern in tropical and subtropical regions. The virus belongs to the genus Flavivirus and has four distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. Each serotype can cause dengue fever, and infection with one serotype provides lifelong immunity to that serotype but not to the others. This article focuses on the recombinant protein known as Dengue Virus Subtype 1 & 3 fused Envelope 58kDa.
The envelope (E) protein of the dengue virus is a critical component for viral entry into host cells. It is responsible for binding to the host cell receptors and facilitating membrane fusion. The E protein is also the primary target for neutralizing antibodies, making it a key focus for vaccine development .
The recombinant Dengue Virus Subtype 1 & 3 fused Envelope 58kDa protein is a fusion of the envelope proteins from DENV-1 and DENV-3. This fusion protein is designed to elicit an immune response that can provide protection against multiple serotypes of the dengue virus. The 58kDa size indicates the molecular weight of the protein, which is a result of the combined sequences from the two serotypes .
Recombinant proteins are typically produced using various expression systems, such as bacterial, yeast, insect, or mammalian cells. The choice of expression system depends on factors like the complexity of the protein, post-translational modifications, and yield requirements. For the Dengue Virus Subtype 1 & 3 fused Envelope 58kDa protein, a common approach is to use baculovirus-insect cell expression systems due to their ability to produce high yields of properly folded and functional proteins .
The purification process involves several steps to ensure the recombinant protein is of high purity and suitable for research or vaccine development. Techniques such as affinity chromatography, ion exchange chromatography, and size-exclusion chromatography are commonly used to achieve this .
The primary application of the Dengue Virus Subtype 1 & 3 fused Envelope 58kDa recombinant protein is in vaccine development. Given the challenges in creating a vaccine that provides balanced protection against all four dengue serotypes, recombinant proteins offer a promising approach. By combining envelope proteins from different serotypes, researchers aim to develop a vaccine that can induce a broad and effective immune response .
Additionally, this recombinant protein can be used in diagnostic assays to detect antibodies against dengue virus in patient samples. It can also serve as a tool for studying the immune response to dengue virus and for screening potential antiviral compounds .
