Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine
| Autor: | Parnal Narvekar, Paulina Andrade, Allan Parker, Daniela Michlmayr, Hansi Dean, Eva Harris, Eduardo J. M. Nascimento |
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| Rok vydání: | 2020 |
| Předmět: |
Serotype
Dengue Vaccines Dengue virus Cross Reactions medicine.disease_cause Antibodies Viral Serogroup Vaccines Attenuated Peripheral blood mononuclear cell Dengue fever Dengue Antibody Specificity Immunology and Allergy Medicine Animals Humans Dengue vaccine B-Lymphocytes Singapore biology business.industry Vaccination Dengue Virus medicine.disease Virology Antibodies Neutralizing Infectious Diseases biology.protein Macaca Antibody business FluoroSpot Immunologic Memory |
| Zdroj: | The Journal of infectious diseases. 223(2) |
| ISSN: | 1537-6613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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