Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection
Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue virus infection remain undefin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2016
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| Online Access: | https://hdl.handle.net/10356/84671 http://hdl.handle.net/10220/41909 |
| _version_ | 1824454020030267392 |
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| author | Xu, Meihui Züst, Roland Toh, Ying Xiu Pfaff, Jennifer M. Kahle, Kristen M. Davidson, Edgar Doranz, Benjamin J. Velumani, Sumathy Tukijan, Farhana Wang, Cheng-I Fink, Katja |
| author2 | Jung, J. U. |
| author_facet | Jung, J. U. Xu, Meihui Züst, Roland Toh, Ying Xiu Pfaff, Jennifer M. Kahle, Kristen M. Davidson, Edgar Doranz, Benjamin J. Velumani, Sumathy Tukijan, Farhana Wang, Cheng-I Fink, Katja |
| author_sort | Xu, Meihui |
| collection | NTU |
| description | Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. In this study, we address the protective capacity of dengue virus-specific antibodies that are produced by plasmablasts a few days after natural secondary infection. Among a panel of 18 dengue virus-reactive human monoclonal antibodies, four groups of antibodies were identified based on their binding properties. While antibodies targeting the fusion loop of the glycoprotein of dengue virus dominated the antibody response, two smaller groups of antibodies bound to previously undescribed epitopes in domain II of the E protein. The latter, largely serotype-cross-reactive antibodies, demonstrated increased stability of binding at pH 5. These antibodies possessed weak to moderate neutralization capacity in vitro but were the most efficacious in promoting the survival of infected mice. Our data suggest that the cross-reactive anamnestic antibody response has a protective capacity despite moderate neutralization in vitro and a moderate decrease of viremia in vivo. |
| first_indexed | 2025-02-19T03:15:40Z |
| format | Journal Article |
| id | ntu-10356/84671 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:15:40Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/846712023-02-28T17:01:08Z Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection Xu, Meihui Züst, Roland Toh, Ying Xiu Pfaff, Jennifer M. Kahle, Kristen M. Davidson, Edgar Doranz, Benjamin J. Velumani, Sumathy Tukijan, Farhana Wang, Cheng-I Fink, Katja Jung, J. U. School of Biological Sciences dengue virus infection antibody Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. In this study, we address the protective capacity of dengue virus-specific antibodies that are produced by plasmablasts a few days after natural secondary infection. Among a panel of 18 dengue virus-reactive human monoclonal antibodies, four groups of antibodies were identified based on their binding properties. While antibodies targeting the fusion loop of the glycoprotein of dengue virus dominated the antibody response, two smaller groups of antibodies bound to previously undescribed epitopes in domain II of the E protein. The latter, largely serotype-cross-reactive antibodies, demonstrated increased stability of binding at pH 5. These antibodies possessed weak to moderate neutralization capacity in vitro but were the most efficacious in promoting the survival of infected mice. Our data suggest that the cross-reactive anamnestic antibody response has a protective capacity despite moderate neutralization in vitro and a moderate decrease of viremia in vivo. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2016-12-21T02:10:15Z 2019-12-06T15:49:13Z 2016-12-21T02:10:15Z 2019-12-06T15:49:13Z 2016 Journal Article Xu, M., Züst, R., Toh, Y. X., Pfaff, J. M., Kahle, K. M., Davidson, E., et al. (2016). Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection. Journal of Virology, 90(24), 11122-11131. 0022-538X https://hdl.handle.net/10356/84671 http://hdl.handle.net/10220/41909 10.1128/JVI.01096-16 en Journal of Virology © 2016 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. 10 p. application/pdf |
| spellingShingle | dengue virus infection antibody Xu, Meihui Züst, Roland Toh, Ying Xiu Pfaff, Jennifer M. Kahle, Kristen M. Davidson, Edgar Doranz, Benjamin J. Velumani, Sumathy Tukijan, Farhana Wang, Cheng-I Fink, Katja Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection |
| title | Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection |
| title_full | Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection |
| title_fullStr | Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection |
| title_full_unstemmed | Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection |
| title_short | Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection |
| title_sort | protective capacity of the human anamnestic antibody response during acute dengue virus infection |
| topic | dengue virus infection antibody |
| url | https://hdl.handle.net/10356/84671 http://hdl.handle.net/10220/41909 |
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