| Autor: |
Behzadi MA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Choi A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Global Health and Emerging Pathogens Institute, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Duehr J; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Feyznezhad R; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Upadhyay C; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Schotsaert M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Global Health and Emerging Pathogens Institute, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Palese P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. raffael.nachbagauer@mssm.edu. |
| Abstrakt: |
Rhinoviruses (RVs) are the main cause of the common cold worldwide. To date, more than 160 types of the virus have been recognized, categorized into three major species - A, B, and C. There are currently no approved vaccines available to prevent infection with RVs. To elicit antibodies against conserved regions located on capsid proteins of RV A viruses, mice were sequentially vaccinated with DNA plasmids encoding capsid proteins of different RV A types. After a final boost with whole virus, antibody-expressing hybridomas were generated. After isotyping, 11 monoclonal antibodies (mAbs) expressing an IgG subtype Fc-domain were selected for further expansion and purification. Three mAbs showed cross-reactivity against multiple strains of RV A viruses by ELISA, including strains A1A, A1B, A15, A16 and A49. Other mAbs had strain-specific binding patterns, with the majority of mAbs showing reactivity to RV-A15, the strain used for the final vaccination. We found that the RV-A15-specific mAbs, but not the cross-reactive mAbs, had neutralizing activity against RV-A15. An antibody dependent cellular phagocytosis (ADCP) assay revealed substantial ADCP activity for one of the cross-reactive mAbs. Epitope mapping of the neutralizing mAbs via escape mutant virus generation revealed a shared binding epitope on VP1 of RV-A15 for several neutralizing mAbs. The epitope of the ADCP-active, non-neutralizing mAb was determined by microarray analysis of peptides generated from the VP1 capsid protein. VP1-specific, cross-reactive antibodies, especially those with ADCP activity, could contribute to protection against RV infections. |
