title: Dengue serotype cross-reactive, anti-e protein antibodies confound specific immune memory for 1 year after infection.
abstract: Dengue virus has four serotypes and is endemic globally in tropical countries. Neither a specific treatment nor an approved vaccine is available, and correlates of protection are not established. The standard neutralization assay cannot differentiate between serotype-specific and serotype cross-reactive antibodies in patients early after infection, leading to an overestimation of the long-term serotype-specific protection of an antibody response. It is known that the cross-reactive response in patients is temporary but few studies have assessed kinetics and potential changes in serum antibody specificity over time. To better define the specificity of polyclonal antibodies during disease and after recovery, longitudinal samples from patients with primary or secondary DENV-2 infection were collected over a period of 1 year. We found that serotype cross-reactive antibodies peaked 3 weeks after infection and subsided within 1 year. Since secondary patients rapidly produced antibodies specific for the virus envelope (E) protein, an E-specific ELISA was superior compared to a virus particle-specific ELISA to identify patients with secondary infections. Dengue infection triggered a massive activation and mobilization of both naïve and memory B cells possibly from lymphoid organs into the blood, providing an explanation for the surge of circulating plasmablasts and the increase in cross-reactive E protein-specific antibodies.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Biopolis , Singapore.
authors.forename: Ying Xiu
authors.initials: YX
authors.lastname: Toh
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital , Singapore , Singapore.
authors.forename: Victor
authors.initials: V
authors.lastname: Gan
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Biopolis , Singapore.
authors.forename: Thavamalar
authors.initials: T
authors.lastname: Balakrishnan
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Biopolis , Singapore.
authors.forename: Roland
authors.initials: R
authors.lastname: Zuest
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Biopolis , Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Biopolis , Singapore.
authors.forename: Solomonraj
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Biopolis , Singapore.
authors.forename: Ramapraba
authors.initials: R
authors.lastname: Appanna
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital , Singapore , Singapore.
authors.forename: Tun Linn
authors.initials: TL
authors.lastname: Thein
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital , Singapore , Singapore.
authors.forename: Adrian Kheng-Yeow
authors.initials: AK
authors.lastname: Ong
authors.affiliation: Environmental Health Institute, National Environment Agency , Singapore , Singapore.
authors.forename: Lee Ching
authors.initials: LC
authors.lastname: Ng
authors.affiliation: Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital , Singapore , Singapore ; Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore ; Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore , Singapore.
authors.forename: Yee Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , Biopolis , Singapore.
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
keywords: B cells; Dengue; antibodies; cross-reactive; longitudinal studies; plasmablasts; vaccines; viral infection