Human monoclonal antibodies that neutralize vaccine and wild-type poliovirus strains.
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.
Lankenau Institute for Medical Research, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
Rama Devudu
RD
Puligedda
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
Diana
D
Kouiavskaia
Lankenau Institute for Medical Research, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA; Immunome, Inc., 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
Sharad P
SP
Adekar
Lankenau Institute for Medical Research, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
Rashmi
R
Sharma
Lankenau Institute for Medical Research, 100 E. Lancaster Ave., Wynnewood, PA 19096, USA.
Chandana
C
Devi Kattala
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
Gennady
G
Rezapkin
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
Bella
B
Bidzhieva
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.
Scott K
SK
Dessain
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. Electronic address: Konstantin.Chumakov@fda.hhs.gov.
Konstantin
K
Chumakov
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification; D003001:Cloning, Molecular; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006801:Humans; D017955:Poliovirus / Q000276:immunology*; D011485:Protein Binding
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes
Antiviral therapeutic; Chronic viral infection; Epitope; Eradication; Neutralization; Poliovirus