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Antiviral Res. 2014 Aug;108:36-43. doi: 10.1016/j.antiviral.2014.05.005. Epub 2014 May 10.

Human monoclonal antibodies that neutralize vaccine and wild-type poliovirus strains.

Author information

1
Lankenau Institute for Medical Research, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
2
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
3
Lankenau Institute for Medical Research, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA; Immunome, Inc., 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
4
Lankenau Institute for Medical Research, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA; Immunome, Inc., 100 E. Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: dessain@limr.org.
5
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. Electronic address: Konstantin.Chumakov@fda.hhs.gov.

Abstract

An essential requirement for eradication of poliomyelitis is the elimination of circulating vaccine derived polioviruses (cVDPV) and polioviruses excreted by chronically infected individuals with immunodeficiencies (iVDPV). As part of a post-eradication risk management strategy, a human monoclonal antibody (mAb) therapeutic could play a role in halting excretion in asymptomatic carriers and could be used, in combination with vaccines and antiviral drugs, to protect polio-exposed individuals. Cross-neutralizing mAbs may be particularly useful, as they would reduce the number of mAbs needed to create a comprehensive PV therapeutic. We cloned a panel of IgG mAbs from OPV-vaccinated, IPV-boosted healthy subjects. Many of the mAbs had potent neutralizing activities against PV wild-type (WT) and Sabin strains, and two of the mAbs, 12F8 and 1E4, were significantly cross-reactive against types 1 and 2 and types 1 and 3, respectively. Mapping the binding epitopes using strains resistant to neutralization (escape mutants) suggested that cross-specific PV binding epitopes may primarily reside within the canyon region, which interacts with the cellular receptor molecule CD155 and the cross-neutralizing chimpanzee/human mAb, A12. Despite their close proximity, the epitopes for the 12F8 and 1E4 mAbs on Sabin 1 were not functionally identical to the A12 epitope. When tested together, 12F8 and 1E4 neutralized a diverse panel of clinically relevant PV strains and did not exhibit interference. Virus mutants resistant to the anti-poliovirus drug V-073 were also neutralized by the mAbs. The 12F8 and 1E4 mAbs may suitable for use as anti-PV therapeutics.

KEYWORDS:

Antiviral therapeutic; Chronic viral infection; Epitope; Eradication; Neutralization; Poliovirus

PMID:
24824031
DOI:
10.1016/j.antiviral.2014.05.005
[Indexed for MEDLINE]
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