title: A single chimpanzee-human neutralizing monoclonal antibody provides post-exposure protection against type 1 and type 2 polioviruses.
abstract: BACKGROUND
  Development of anti-poliovirus therapies to complement vaccination is an urgent priority. A number of antiviral drugs are in development. Recently we have developed human monoclonal antibodies that could be used for treatment of chronically infected individuals and emergency response to potential reappearance of polioviruses after eradication.
  
  
  OBJECTIVE
  The aim of this study was to characterize neutralizing activity of anti-poliovirus monoclonal antibody A12 against wild type, vaccine-derived, and drug-resistant poliovirus strains, evaluate in vivo pre- and post-exposure protective properties of the antibody against polioviruses of serotypes 1 and 2, and to determine whether it interferes with response to immunization with poliovirus vaccine.
  
  
  METHODS
  Immunogenicity studies were performed in CD1 mice. Poliovirus neutralizing titers were determined in poliovirus microneutralization assay. Poliovirus immunization-challenge experiments were performed in poliovirus-susceptible TgPVR21 mice.
  
  
  RESULTS
  We show that monoclonal antibody A12 effectively neutralizes in vitro a broad range of type 1 and type 2 wild and vaccine-derived polioviruses, provides effective pre- and post-exposure protection of TgPVR21 mice from challenge with a lethal dose of poliovirus. Treatment of animals with the antibody concurrent with IPV immunization does not prevent immune response to the vaccine.
  
  
  CONCLUSIONS
  Anti-poliovirus antibody A12 effectively neutralizes a range of wild and VDPV strains and protectstransgenic mice susceptible to poliovirus against lethal challenge upon pre- and post-exposure administration. This suggests that the antibodies could be used in combination with drugs and/or vaccine to improve their efficacy and prevent emergence of resistant variants, and provides a justification for initiating their clinical evaluation.
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 52, Room 1126, Silver Spring, MD 20993-0002, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Kouiavskaia
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Zhaochun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 52, Room 1126, Silver Spring, MD 20993-0002, USA.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Dragunsky
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 52, Room 1126, Silver Spring, MD 20993-0002, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Mirochnitchenko
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Purcell
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 52, Room 1126, Silver Spring, MD 20993-0002, USA. Electronic address: konstantin.chumakov@fda.hhs.gov.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chumakov
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D002679:Pan troglodytes; D011051:Poliomyelitis / Q000517:prevention & control*; D017955:Poliovirus / Q000276:immunology*; D056990:Post-Exposure Prophylaxis; D065129:Pre-Exposure Prophylaxis; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing
keywords: Antiviral therapy; Chronic virus excretors; Drug-resistance; Emergency prophylaxis; Polio eradication