Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

• DOI: 10.1128/jvi.01190-10
• Publication Date: 2010-08-12T02:28:22Z
• Authors: James D. Brien; S. Kyle Austin; Soila Sukupolvi-P...; Katie M. O'Brien; Syd Johnson; Daved H. Fremont; Michael S. Diamond
• Keywords: Heterologous; Dengue vaccine

Dengue viruses (DENV) comprise a family of related positive-strand RNA that infect up to 100 million people annually. Currently, there is no approved vaccine or therapy prevent infection diminish disease severity. Protection against DENV associated with the development neutralizing antibodies recognize viral envelope (E) protein. Here, goal identifying monoclonal (MAbs) can function as postexposure therapy, we generated panel 82 new MAbs DENV-3, including 24 highly MAbs. Using yeast surface display, localized epitopes most strongly lateral ridge domain III (DIII) type 3 (DENV-3) E While several functioned prophylactically DENV-3-induced lethality in stringent intracranial-challenge model mice, only three exhibited therapeutic activity homologous strain when administered 2 days after infection. Remarkably, MAb our protected challenge by from heterologous DENV-3 genotype. Consistent this, single neutralized efficiently nine different strains used this study, likely because sequence variation DIII within and between genotypes. Our studies suggest diversity may limit efficacy tetravalent vaccines DENV, neutralization potency generally correlated narrowed genotype specificity.