title: Neutralization of dengue virus in the presence of Fc receptor-mediated phagocytosis distinguishes serotype-specific from cross-neutralizing antibodies.
abstract: Although several vaccine candidates are presently in various phases of clinical trials, the field still lacks an effective tool to determine protective immunity. The presence of cross-neutralizing antibodies limits a serological approach to identify the etiology and distinguish lifelong from short-lived humoral protection. A recent study indicated that cross-reactive but not serotype-specific antibodies require high antibody concentration to co-ligate FcγRIIB and inhibit infection. Here, we tested if these differences could allow us to distinguish serotype-specific from cross-neutralizing antibodies. Using 30 blinded early convalescent serum samples from patients with virologically confirmed dengue, we demonstrate that neutralization in the presence of FcγR-mediated phagocytosis in THP-1 correctly identifies the DENV serotype of the infection in 93.3% of the cases compared to 76.7% with plaque reduction neutralization test. Our findings could provide a new approach for evaluating DENV neutralization and suggest that in addition to blocking specific ligand-receptor interactions for viral entry, antibodies must prevent viral uncoating during FcγR-mediated phagocytosis for complete humoral protection.
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 169854 Singapore, Singapore.
authors.forename: Ryan S L
authors.initials: RS
authors.lastname: Wu
authors.forename: Kuan Rong
authors.initials: KR
authors.lastname: Chan
authors.forename: Hwee Cheng
authors.initials: HC
authors.lastname: Tan
authors.forename: Angelia
authors.initials: A
authors.lastname: Chow
authors.forename: John C
authors.initials: JC
authors.lastname: Allen
authors.forename: Eng Eong
authors.initials: EE
authors.lastname: Ooi
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D045744:Cell Line, Tumor; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009500:Neutralization Tests / Q000379:methods; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology*; D012680:Sensitivity and Specificity; D013045:Species Specificity; D010948:Viral Plaque Assay; D053586:Virus Internalization
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG