title: Dissecting Antibodies Induced by a Chimeric Yellow Fever-Dengue, Live-Attenuated, Tetravalent Dengue Vaccine (CYD-TDV) in Naive and Dengue-Exposed Individuals.
abstract: Sanofi Pasteur has developed a chimeric yellow fever-dengue, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is currently approved for use in several countries. In clinical trials, CYD-TDV was efficacious at reducing laboratory-confirmed cases of dengue disease. Efficacy varied by dengue virus (DENV) serotype and prevaccination dengue immune status. We compared the properties of antibodies in naive and DENV-exposed individuals who received CYD-TDV. We depleted specific populations of DENV-reactive antibodies from immune serum samples to estimate the contribution of serotype-cross-reactive and type-specific antibodies to neutralization. Subjects with no preexisting immunity to DENV developed neutralizing antibodies to all 4 serotypes of DENV. Further analysis demonstrated that DENV4 was mainly neutralized by type-specific antibodies whereas DENV1, DENV2, and DENV3 were mainly neutralized by serotype cross-reactive antibodies. When subjects with preexisting immunity to DENV were vaccinated, they developed higher levels of neutralizing antibodies than naive subjects who were vaccinated. In preimmune subjects, CYD-TDV boosted cross-reactive neutralizing antibodies while maintaining type-specific neutralizing antibodies acquired before vaccination. Our results demonstrate that the quality of neutralizing antibodies induced by CYD-TDV varies depending on DENV serotype and previous immune status. We discuss the implications of these results for understanding vaccine efficacy.
authors.affiliation: Department of Microbiology and Immunology and.
authors.forename: Sandra
authors.initials: S
authors.lastname: Henein
authors.affiliation: Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill.
authors.forename: Jesica
authors.initials: J
authors.lastname: Swanstrom
authors.affiliation: Sanofi Pasteur, Orlando, Florida.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Byers
authors.affiliation: Sanofi Pasteur, Orlando, Florida.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Moser
authors.affiliation: Sanofi Pasteur, Orlando, Florida.
authors.forename: S Farzana
authors.initials: SF
authors.lastname: Shaik
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bonaparte
authors.affiliation: Sanofi Pasteur, Lyon, France.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jackson
authors.affiliation: Sanofi Pasteur, Lyon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Guy
authors.affiliation: Department of Microbiology and Immunology and.|Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill.
authors.forename: Ralph
authors.initials: R
authors.lastname: Baric
authors.affiliation: Department of Microbiology and Immunology and.
authors.forename: Aravinda M
authors.initials: AM
authors.lastname: de Silva
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D002460:Cell Line; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control; D053059:Dengue Vaccines / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology; D006801:Humans; D000071497:Immunogenicity, Vaccine; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014613:Vaccines, Attenuated
keywords: Dengue vaccine; flavivirus; live attenuated vaccine.; neutralizing antibody