In vitro antiviral activity of single domain antibody fragments against poliovirus.
VHHs or Nanobodies are single-domain antigen-binding fragments derived from heavy chain antibodies found in camelids. It has already been shown that complex protein mixtures and even whole organisms elicit good immune responses in camelids; therefore we hypothesized that VHHs selected from a dromedary immunized with poliovirus type 1 might inhibit the in vitro replication of poliovirus through binding to essential biological sites on the viral capsid. In this study, we aimed to determine whether VHHs inhibit wild-type and vaccine strains of poliovirus type 1. Interestingly, VHHs showed a potent antipolio activity with EC50 values in the low nanomolar range. Moreover, these antibody fragments completely blocked viral multiplication at higher concentrations. Remarkably, no (immune) escape variants against some of these VHHs could be generated. In conclusion, VHHs fulfil several in vitro requirements to be assigned as potential antiviral compounds for further development of an anti-poliovirus drugs.
Thys
Bert
B
Department of Pharmaceutical Biotechnology and Molecular Biology, Centre for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. bert.thys@vub.ac.be
Schotte
Lise
L
Muyldermans
Serge
S
Wernery
Ulrich
U
Hassanzadeh-Ghassabeh
Gholamreza
G
Rombaut
Bart
B
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002162:Camelus; D006367:HeLa Cells; D006801:Humans; D007128:Immunoglobulin Fragments / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D017955:Poliovirus / Q000187:drug effects* / Q000254:growth & development; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D007128:Immunoglobulin Fragments