Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses
| Autor: | Jianzhu Chen, Jue Hou, Weijian Ye, Lan Hiong Wong, Hooi Linn Loo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunoglobulin gene lcsh:Immunologic diseases. Allergy animal diseases Immunology chemical and pharmacologic phenomena Dengue Vaccines Dengue virus medicine.disease_cause Epitope Dengue 03 medical and health sciences epitope-decreasing Epitopes Mice 0302 clinical medicine Immune system Antigen medicine Immunology and Allergy Animals Neutralizing antibody Antigens Viral Original Research biology dengue virus Vaccination biochemical phenomena metabolism and nutrition Virology Mice Inbred C57BL 030104 developmental biology Immunization vaccine development sequential immunization biology.protein bacteria immunoglobulin diversification Antibody lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 11 (2020) |
| ISSN: | 1664-3224 |
| Popis: | Repeated homologous antigen immunization has been hypothesized to hinder antibody diversification, whereas sequential immunization with heterologous immunogens can educate B cell differentiations towards conserved residues thereby facilitating the generation of cross-reactive immunity. In this study, we developed a sequential vaccination strategy that utilized epitope-decreasing antigens to reinforce the cross-reactivity of T and B cell immune responses against all four serotypes dengue virus. The epitope-decreasing immunization was implemented by sequentially inoculating mice with antigens of decreasing domain complexity that first immunized with DENV1 live-attenuated virus, following by the Envelope protein (Env), and then Env domain III (EDIII) subunit protein. When compared to mice immunized with DENV1 live-attenuated virus three times, epitope-decreasing immunization induced higher TNF-α CD8+ T cell immune response against consensus epitopes. Epitope-decreasing immunization also significantly improved neutralizing antibody response to heterologous serotypes. Moreover, this sequential approach promoted somatic hypermutations in the immunoglobulin gene of antigen-specific memory B cells in comparison to repeated immunization. This proof-of-concept work on epitope-decreasing sequential vaccination sheds light on how successively exposing the immune system to decreasing-epitope antigens can better induce cross-reactive antibodies. |
| Databáze: | OpenAIRE |
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