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- Title
Ribosome display for the rapid generation of high-affinity Zika-neutralizing single-chain antibodies.
- Authors
Kunamneni, Adinarayana; Ye, Chunyan; Bradfute, Steven B.; Durvasula, Ravi
- Abstract
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.
- Subjects
ZIKA virus infections; VIRAL disease diagnosis; IMMUNOGLOBULINS; NEUTRALIZATION (Chemistry); VIRAL proteins
- Publication
PLoS ONE, 2018, Vol 13, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0205743