Academic Journal
Ribosome display for the rapid generation of high-affinity Zika-neutralizing single-chain antibodies.
| Title: | Ribosome display for the rapid generation of high-affinity Zika-neutralizing single-chain antibodies. |
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| Authors: | Adinarayana Kunamneni, Chunyan Ye, Steven B Bradfute, Ravi Durvasula |
| Source: | PLoS ONE, Vol 13, Iss 11, p e0205743 (2018) |
| Publisher Information: | Public Library of Science (PLoS), 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Medicine, Science |
| More Details: | BACKGROUND:Zika virus (ZIKV) is an emerging pathogen with no approved therapeutics and only limited diagnostics available. To address this gap, six mouse single-chain antibodies (scFvs) to ZIKV envelope (E) protein were isolated rapidly and efficiently from a ribosome-displayed antibody library constructed from the spleens of five immunized mice. METHODOLOGY/RESULTS:In this report, we have generated a panel of mouse scFvs to ZIKV E protein using ribosome display. The six scFvs demonstrated no cross-reactivity with DENV2 NGC envelope protein, suggesting specificity for ZIKV E protein. These scFvs showed differences in their affinity: two (scFv45-3, scFv63-1) of them were dominant after four rounds of panning, and showed higher affinity (an apparent Kd values from 19 to 27 nM) than the other four (scFv5-1, scFv7-2, scFv38-1, and scFv51-2). All six scFvs showed ZIKV-neutralizing activity in the plaque reduction neutralization test (PRNT) assay and their neutralizing activity was positively correlated with their affinities. CONCLUSIONS/SIGNIFICANCE:The scFvs (45-3 and 63-1) with highest affinity may have dual utility as diagnostics capable of recognizing ZIKV E subtypes and may be further developed to treat ZIKV infection. Our approach has the added advantage of generating Fc receptor-deficient antibodies, minimizing concern of antibody-dependent enhancement (ADE) of infection. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC6239285?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0205743 |
| Access URL: | https://doaj.org/article/8f90957a61ef480bb0bf2c1b9e05547f |
| Accession Number: | edsdoj.8f90957a61ef480bb0bf2c1b9e05547f |
| Database: | Directory of Open Access Journals |
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| ISSN: | 19326203 |
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| DOI: | 10.1371/journal.pone.0205743 |
| Published in: | PLoS ONE |
| Language: | English |