title: Conservation of the DENV-2 type-specific and DEN complex-reactive antigenic sites among DENV-2 genotypes.
abstract: The envelope (E) protein is composed of three domains (ED1, ED2 and ED3) with ED3 targeted by the most potent neutralizing antibodies. DENV-2 strains can be divided into six genotypes. Comparison of ED3 of representative strains of the six genotypes revealed that there are nine variable residues that are specific to a given genotype. Recombinant ED3s (rED3s) of six different DENV-2 strains representing all nine variable residues were expressed, and their reactivity against a panel of two DENV-2 type-specific and three DENV complex-reactive monoclonal antibodies (mAbs) were compared. The differences in binding affinity to the rED3s representing different DENV-2 genotypes were relatively small, with the exception of type-specific-mAb 3H5 that showed up to 10-fold differences in binding between genotypes. Overall the binding differences did not lead to detectable differences in neutralization. Based on these results, DENV-2 ED3-specific neutralizing antibodies will likely be effective against DENV-2 strains from all six genotypes.
authors.affiliation: Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-0436, USA.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Pitcher
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gromowski
authors.forename: David W C
authors.initials: DW
authors.lastname: Beasley
authors.forename: Alan D T
authors.initials: AD
authors.lastname: Barrett
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D014764:Viral Proteins