title: Human monoclonal antibodies derived from memory B cells following live attenuated dengue virus vaccination or natural infection exhibit similar characteristics.
abstract: The immunopathogenesis of severe dengue is poorly understood, but there is concern that induction of cross-reactive nonneutralizing antibodies by infection or vaccination may increase the likelihood of severe disease during a subsequent infection. We generated a total of 63 new human monoclonal antibodies to compare the B-cell response of subjects who received the National Institutes of Health live attenuated dengue vaccine rDEN1Δ30 to that of subjects following symptomatic primary infection with DENV1. Both infection and vaccination induced serum neutralizing antibodies and DENV1-reactive peripheral blood B cells, but the magnitude of induction was lower in vaccinated individuals. Serotype cross-reactive weakly neutralizing antibodies dominated the response in both vaccinated and naturally infected subjects. Antigen specificities were very similar, with a slightly greater percentage of antibodies targeting E protein domain I/II than domain III. These data shed light on the similarity of human B-cell response to live attenuated DENV vaccine or natural infection.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
authors.forename: Ruklanthi
authors.initials: R
authors.lastname: de Alwis
authors.forename: Nurgun
authors.initials: N
authors.lastname: Kose
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Whitehead
authors.forename: Aravinda M
authors.initials: AM
authors.lastname: de Silva
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D019067:Antibody-Dependent Enhancement; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002140:California; D002460:Cell Line; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D009500:Neutralization Tests; D009657:North Carolina; D011994:Recombinant Proteins; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D053059:Dengue Vaccines; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated
keywords: B cells; antibodies; antibody-dependent enhancement; dengue virus; human; hybridomas; neutralization