DENV Specific Neutra™ Antibody Products

Dengue virus (DENV) is a single positive-sense RNA (+ssRNA) virus transmitted by mosquitoes. DENV is the cause of dengue fever. In severe cases, it can progress to dengue hemorrhagic fever and dengue shock syndrome, which have significant morbidity and fatality rates. DENV is usually spherical and mainly consists of +ssRNA, capsid (C) protein, and envelope (E) protein. It belongs to a subgroup of serotypes in the Flaviviridae family with four serotypes, DENV1~4, depending on antigenicity. DENV binds to receptors on the surface of sensitive cells and then enters the cells by cellular phagocytosis and membrane fusion. Finally, it decapsulates and releases the viral RNA under the action of lysosomal enzymes.

Its Gene ID: 1494449, UniProtKB ID: A0A411DW34, and OMIM ID: 614371.

Pathogenesis of DENV

DENV triggers the production of a wide range of cross-reactive antibodies during the initial infection, many of which have limited or no ability to neutralize the virus. These heterotypic antibodies or subneutralizing antibodies bind to viral particles to form virus-antibody complexes. They are internalized into myeloid cells by binding through the Fc receptor (FcR) of IgG, resulting in monocyte-macrophage infections and antibody-dependent enhancement (ADE) effects. In addition, DENV infection can activate various types of T cells and release cytokines including IL-2, IFN-γ, histamine, and allergens C3a and C5a. This cascade of immune responses can worsen the symptoms of the infection, potentially leading to shock, circulatory failure, and hemorrhage.

Fig.1 Pathogenesis and ADE of DENV.¹

Neutralizing Antibodies Targeting DENV E Protein

Since the use of polyclonal antibodies carries a significant risk of ADE, monoclonal antibodies (mAbs) have certain unique advantages in dengue therapy. The E protein, which is commonly known as a target for neutralizing antibodies, is present in 180 copies on the outer surface of DENV. The majority of DENV E protein mAbs primarily target structural domain III epitopes, for which they are mostly serotype-specific. Structural domain III of the E protein is involved in binding DENV to the surface of host cells to mediate viral entry. Therefore, these antibodies can inhibit viral replication by blocking viral binding to host cell receptors and potential endocytosis. Research has shown that certain mAbs to DENV E proteins targeting the FL loop of structural domain II and the A chain of structural domain III do not have any ADE effect.

Fig.2 MAbs targeting DENV E protein.¹

Creative Biolabs offers 8 different anti-DENV neutralizing antibody products to our global customers. These antibodies target different serotypes of DENV and can be used in ELISA, IF, WB, etc.

REFERENCE

1. Sarker, Animesh, Nidhi Dhama, and Rinkoo Devi Gupta. "Dengue virus neutralizing antibody: a review of targets, cross-reactivity, and antibody-dependent enhancement." Frontiers in immunology 14 (2023): 1200195. Distributed under open access license CC BY 4.0, without modification.