Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine.
J Infect Dis
; 223(2): 247-257, 2021 02 03.
Article
em En
| MEDLINE
| ID: mdl-32572472
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vacinas Atenuadas
/
Linfócitos B
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Dengue
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Vírus da Dengue
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Vacinas contra Dengue
Tipo de estudo:
Clinical_trials
Limite:
Animals
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Humans
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article