Daniela Michlmayr1, Paulina Andrade1,2, Eduardo J M Nascimento3, Allan Parker3, Parnal Narvekar1, Hansi J Dean3, Eva Harris1. 1. Division of Infectious Diseases and Vaccinology, School of Public Health, University of California Berkeley, Berkeley, California, USA. 2. Universidad San Francisco de Quito, Colegio de Ciencias Biológicas y Ambientales, Quito, Ecuador. 3. Takeda Vaccines, Inc., Cambridge, Massachusetts, USA.
Abstract
BACKGROUND: Dengue is caused by 4 antigenically distinct serotypes of dengue virus (DENV1-4). Takeda's live attenuated tetravalent dengue vaccine (TAK-003) candidate is composed of an attenuated DENV2 and chimeric viruses containing prM/E of DENV1, 3 and 4 on the DENV2 backbone. The multicolor FluoroSpot (MCF) assay enables quantitation of serotype-specific and cross-reactive individual memory B cells (MBCs) secreting DENV-specific antibodies in a polyclonal mixture. METHODS: Using the MCF assay, we determined the type-specific and cross-reactive MBC response in peripheral blood mononuclear cells collected pre- and postvaccination from 7 macaques and 15 randomly selected individuals who received TAK-003 (8 DENV seronegative and 7 DENV seropositive) in a phase 2 clinical trial in Singapore (DEN-205 study). RESULTS: Preexisting DENV-specific MBC responses were detected only in seropositive vaccine recipients at day 0. Following vaccination, both type-specific and cross-reactive MBCs to all 4 DENV serotypes were observed in all macaques and clinical trial participants. The proportion of type-specific MBCs was higher than cross-reactive MBCs and remained stable between day 30 and 360 post vaccination. CONCLUSIONS: These results demonstrate that, unlike primary or secondary natural DENV infection, tetravalent vaccination elicits tetravalent type-specific MBCs, and thus all 4 components of TAK-003 contribute to the DENV-specific MBC response following vaccination. CLINICAL TRIALS REGISTRATION: NCT02425098.
BACKGROUND: Dengue is caused by 4 antigenically distinct serotypes of dengue virus (DENV1-4). Takeda's live attenuated tetravalent dengue vaccine (TAK-003) candidate is composed of an attenuated DENV2 and chimeric viruses containing prM/E of DENV1, 3 and 4 on the DENV2 backbone. The multicolor FluoroSpot (MCF) assay enables quantitation of serotype-specific and cross-reactive individual memory B cells (MBCs) secreting DENV-specific antibodies in a polyclonal mixture. METHODS: Using the MCF assay, we determined the type-specific and cross-reactive MBC response in peripheral blood mononuclear cells collected pre- and postvaccination from 7 macaques and 15 randomly selected individuals who received TAK-003 (8 DENV seronegative and 7 DENV seropositive) in a phase 2 clinical trial in Singapore (DEN-205 study). RESULTS: Preexisting DENV-specific MBC responses were detected only in seropositive vaccine recipients at day 0. Following vaccination, both type-specific and cross-reactive MBCs to all 4 DENV serotypes were observed in all macaques and clinical trial participants. The proportion of type-specific MBCs was higher than cross-reactive MBCs and remained stable between day 30 and 360 post vaccination. CONCLUSIONS: These results demonstrate that, unlike primary or secondary natural DENVinfection, tetravalent vaccination elicits tetravalent type-specific MBCs, and thus all 4 components of TAK-003 contribute to the DENV-specific MBC response following vaccination. CLINICAL TRIALS REGISTRATION: NCT02425098.
Authors: Robert K M Choy; A Louis Bourgeois; Christian F Ockenhouse; Richard I Walker; Rebecca L Sheets; Jorge Flores Journal: Clin Microbiol Rev Date: 2022-07-06 Impact factor: 50.129
Authors: Pongsakorn Thawornpan; Siriruk Changrob; Piyawan Kochayoo; Kittikorn Wangriatisak; Francis B Ntumngia; Sai Lata De; Eun-Taek Han; John H Adams; Patchanee Chootong Journal: PLoS One Date: 2022-10-18 Impact factor: 3.752