Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses
© Copyright © 2020 Hou, Ye, Loo, Wong and Chen. 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 gene...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media SA
2021
|
| Online Access: | https://hdl.handle.net/1721.1/134376 |
| _version_ | 1826188143377776640 |
|---|---|
| author | Hou, Jue Ye, Weijian Loo, Hooi Linn Wong, Lan Hiong Chen, Jianzhu |
| author2 | Singapore-MIT Alliance in Research and Technology (SMART) |
| author_facet | Singapore-MIT Alliance in Research and Technology (SMART) Hou, Jue Ye, Weijian Loo, Hooi Linn Wong, Lan Hiong Chen, Jianzhu |
| author_sort | Hou, Jue |
| collection | MIT |
| description | © Copyright © 2020 Hou, Ye, Loo, Wong and Chen. 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. |
| first_indexed | 2024-09-23T07:55:14Z |
| format | Article |
| id | mit-1721.1/134376 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T07:55:14Z |
| publishDate | 2021 |
| publisher | Frontiers Media SA |
| record_format | dspace |
| spelling | mit-1721.1/1343762023-02-17T19:55:25Z Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses Hou, Jue Ye, Weijian Loo, Hooi Linn Wong, Lan Hiong Chen, Jianzhu Singapore-MIT Alliance in Research and Technology (SMART) Koch Institute for Integrative Cancer Research at MIT © Copyright © 2020 Hou, Ye, Loo, Wong and Chen. 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. 2021-10-27T20:04:42Z 2021-10-27T20:04:42Z 2020 2021-07-15T15:50:07Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134376 en 10.3389/fimmu.2020.585133 Frontiers in Immunology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Frontiers Media SA Frontiers |
| spellingShingle | Hou, Jue Ye, Weijian Loo, Hooi Linn Wong, Lan Hiong Chen, Jianzhu Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses |
| title | Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses |
| title_full | Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses |
| title_fullStr | Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses |
| title_full_unstemmed | Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses |
| title_short | Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses |
| title_sort | successive immunization with epitope decreasing dengue antigens induced conservative anti dengue immune responses |
| url | https://hdl.handle.net/1721.1/134376 |
| work_keys_str_mv | AT houjue successiveimmunizationwithepitopedecreasingdengueantigensinducedconservativeantidengueimmuneresponses AT yeweijian successiveimmunizationwithepitopedecreasingdengueantigensinducedconservativeantidengueimmuneresponses AT loohooilinn successiveimmunizationwithepitopedecreasingdengueantigensinducedconservativeantidengueimmuneresponses AT wonglanhiong successiveimmunizationwithepitopedecreasingdengueantigensinducedconservativeantidengueimmuneresponses AT chenjianzhu successiveimmunizationwithepitopedecreasingdengueantigensinducedconservativeantidengueimmuneresponses |