Background: Dengue virus serotypes 1-4 (DENV-1-4) are the most common vector-borne viral pathogens of humans and the etiological agents of dengue fever and dengue hemorrhagic syndrome. A live-attenuated tetravalent dengue vaccine (TDV) developed by Takeda Vaccines has recently progressed to phase 3 safety and efficacy evaluation. Methods: We analyzed the qualitative features of the neutralizing antibody (nAb) response induced in naive and DENV-immune individuals after TDV administration. Using DENV-specific human monoclonal antibodies (mAbs) and recombinant DENV displaying different serotype-specific Ab epitopes, we mapped the specificity of TDV-induced nAbs against DENV-1-3. Results: Nearly all subjects had high levels of DENV-2-specific nAbs directed to epitopes centered on domain III of the envelope protein. In some individuals, the vaccine induced nAbs that tracked with a DENV-1-specific neutralizing epitope centered on domain I of the envelope protein. The vaccine induced binding Abs directed to a DENV-3 type-specific neutralizing epitope, but findings of mapping of DENV-3 type-specific nAbs were inconclusive. Conclusion: Here we provide qualitative measures of the magnitude and epitope specificity of the nAb responses to TDV. This information will be useful for understanding the performance of TDV in clinical trials and for identifying correlates of protective immunity.
RCT Entities:
Background: Dengue virus serotypes 1-4 (DENV-1-4) are the most common vector-borne viral pathogens of humans and the etiological agents of dengue fever and dengue hemorrhagic syndrome. A live-attenuated tetravalent dengue vaccine (TDV) developed by Takeda Vaccines has recently progressed to phase 3 safety and efficacy evaluation. Methods: We analyzed the qualitative features of the neutralizing antibody (nAb) response induced in naive and DENV-immune individuals after TDV administration. Using DENV-specific human monoclonal antibodies (mAbs) and recombinant DENV displaying different serotype-specific Ab epitopes, we mapped the specificity of TDV-induced nAbs against DENV-1-3. Results: Nearly all subjects had high levels of DENV-2-specific nAbs directed to epitopes centered on domain III of the envelope protein. In some individuals, the vaccine induced nAbs that tracked with a DENV-1-specific neutralizing epitope centered on domain I of the envelope protein. The vaccine induced binding Abs directed to a DENV-3 type-specific neutralizing epitope, but findings of mapping of DENV-3 type-specific nAbs were inconclusive. Conclusion: Here we provide qualitative measures of the magnitude and epitope specificity of the nAb responses to TDV. This information will be useful for understanding the performance of TDV in clinical trials and for identifying correlates of protective immunity.
Authors: Usha K Nivarthi; Nurgun Kose; Gopal Sapparapu; Douglas Widman; Emily Gallichotte; Jennifer M Pfaff; Benjamin J Doranz; Daniela Weiskopf; Alessandro Sette; Anna P Durbin; Steve S Whitehead; Ralph Baric; James E Crowe; Aravinda M de Silva Journal: J Virol Date: 2017-02-14 Impact factor: 5.103
Authors: Leah C Katzelnick; Judith M Fonville; Gregory D Gromowski; Jose Bustos Arriaga; Angela Green; Sarah L James; Louis Lau; Magelda Montoya; Chunling Wang; Laura A VanBlargan; Colin A Russell; Hlaing Myat Thu; Theodore C Pierson; Philippe Buchy; John G Aaskov; Jorge L Muñoz-Jordán; Nikos Vasilakis; Robert V Gibbons; Robert B Tesh; Albert D M E Osterhaus; Ron A M Fouchier; Anna Durbin; Cameron P Simmons; Edward C Holmes; Eva Harris; Stephen S Whitehead; Derek J Smith Journal: Science Date: 2015-09-18 Impact factor: 47.728
Authors: Sri Rezeki Hadinegoro; Jose Luis Arredondo-García; Maria Rosario Capeding; Carmen Deseda; Tawee Chotpitayasunondh; Reynaldo Dietze; H I Hj Muhammad Ismail; Humberto Reynales; Kriengsak Limkittikul; Doris Maribel Rivera-Medina; Huu Ngoc Tran; Alain Bouckenooghe; Danaya Chansinghakul; Margarita Cortés; Karen Fanouillere; Remi Forrat; Carina Frago; Sophia Gailhardou; Nicholas Jackson; Fernando Noriega; Eric Plennevaux; T Anh Wartel; Betzana Zambrano; Melanie Saville Journal: N Engl J Med Date: 2015-07-27 Impact factor: 91.245
Authors: Sandra Henein; Jesica Swanstrom; Anthony M Byers; Janice M Moser; S Farzana Shaik; Matthew Bonaparte; Nicholas Jackson; Bruno Guy; Ralph Baric; Aravinda M de Silva Journal: J Infect Dis Date: 2017-02-01 Impact factor: 5.226
Authors: Guntur Fibriansah; Kristie D Ibarra; Thiam-Seng Ng; Scott A Smith; Joanne L Tan; Xin-Ni Lim; Justin S G Ooi; Victor A Kostyuchenko; Jiaqi Wang; Aravinda M de Silva; Eva Harris; James E Crowe; Shee-Mei Lok Journal: Science Date: 2015-07-03 Impact factor: 47.728
Authors: Guntur Fibriansah; Joanne L Tan; Scott A Smith; Ruklanthi de Alwis; Thiam-Seng Ng; Victor A Kostyuchenko; Ramesh S Jadi; Petra Kukkaro; Aravinda M de Silva; James E Crowe; Shee-Mei Lok Journal: Nat Commun Date: 2015-02-20 Impact factor: 14.919
Authors: Guntur Fibriansah; Joanne L Tan; Scott A Smith; Adamberage R de Alwis; Thiam-Seng Ng; Victor A Kostyuchenko; Kristie D Ibarra; Jiaqi Wang; Eva Harris; Aravinda de Silva; James E Crowe; Shee-Mei Lok Journal: EMBO Mol Med Date: 2014-01-13 Impact factor: 12.137
Authors: Ellen Young; Robert H Carnahan; Daniela V Andrade; Nurgun Kose; Rachel S Nargi; Ethan J Fritch; Jennifer E Munt; Michael P Doyle; Laura White; Thomas J Baric; Mark Stoops; Aravinda DeSilva; Longping V Tse; David R Martinez; Deanna Zhu; Stefan Metz; Marcus P Wong; Diego A Espinosa; Magelda Montoya; Scott B Biering; Soila Sukulpolvi-Petty; Guillermina Kuan; Angel Balmaseda; Michael S Diamond; Eva Harris; James E Crowe; Ralph S Baric Journal: Cell Host Microbe Date: 2020-05-13 Impact factor: 21.023
Authors: Laura J White; Ellen F Young; Mark J Stoops; Sandra R Henein; Elizabeth C Adams; Ralph S Baric; Aravinda M de Silva Journal: PLoS Negl Trop Dis Date: 2021-03-12
Authors: Daniela V Andrade; Colin Warnes; Ellen Young; Leah C Katzelnick; Angel Balmaseda; Aravinda M de Silva; Ralph S Baric; Eva Harris Journal: Sci Rep Date: 2019-11-07 Impact factor: 4.379
Authors: Huy A Tu; Usha K Nivarthi; Nancy R Graham; Philip Eisenhauer; Matthew J Delacruz; Kristen K Pierce; Stephen S Whitehead; Jonathan E Boyson; Jason W Botten; Beth D Kirkpatrick; Anna P Durbin; Aravinda M deSilva; Sean A Diehl Journal: Cell Rep Med Date: 2020-12-22