Banerjee, S. and Shi, H. and Banasik, M. and Moon, H. and Lees, W. and Qin, Y. and Harley, A. and Shepherd, Adrian J. and Cho, M.W. (2017) Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region. Virology 505 , pp. 113-126. ISSN 0042-6822.
Abstract
The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone. MPER-specific rabbit monoclonal antibodies were generated, including 9F6. Although it lacked neutralizing activity, the target epitope profile of 9F6 closely resembled those of 4E10 and 10E8 (671NWFDITNWLWYIK683). B-cell repertoire analyses suggested the importance of co-immunizations for maturation of 9F6, which warrants further evaluation of our IPAS-RAM vaccine strategy using an improved priming immunogen.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | HIV-1, Vaccine, gp41, MPER, Rabbit, Neutralizing antibody, Antibody maturation, Next-generation sequencing, NGS |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Data Analytics, Birkbeck Institute for |
| Depositing User: | Administrator |
| Date Deposited: | 10 Mar 2017 14:09 |
| Last Modified: | 02 Aug 2023 17:32 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/18320 |
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