| Autor: |
Lanning S; Department of Molecular Cell and Developmental Biology, University of California Santa Cruz.; Department of Biomolecular Engineering, University of California Santa Cruz., Aguilar-Hernández N; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México., Serrão VHB; Biomolecular Cryo-electron Microscopy Facility, University of California Santa Cruz.; Department of Chemistry and Biochemistry, University of California Santa Cruz., López T; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México., O'Rourke SM; Department of Biomolecular Engineering, University of California Santa Cruz., Lentz A; Department of Biomolecular Engineering, University of California Santa Cruz., Ricemeyer L; Department of Biomolecular Engineering, University of California Santa Cruz., Espinosa R; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México., López S; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México., Arias CF; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México., DuBois RM; Department of Biomolecular Engineering, University of California Santa Cruz. |
| Abstrakt: |
Human astroviruses (HAstVs) are a leading cause of viral childhood diarrhea that infect nearly every individual during their lifetime. Although human astroviruses are highly prevalent, no approved vaccine currently exists. Antibody responses appear to play an important role in protection from HAstV infection, however knowledge about the neutralizing epitope landscape is lacking, as only 3 neutralizing antibody epitopes have previously been determined. Here, we structurally define the epitopes of 3 uncharacterized HAstV-neutralizing monoclonal antibodies: antibody 4B6 with X-ray crystallography to 2.67 Å, and antibodies 3H4 and 3B4 simultaneously with single-particle cryogenic-electron microscopy to 3.33 Å. We assess the epitope locations relative to conserved regions on the capsid spike and find that while antibodies 4B6 and 3B4 target the upper variable loop regions of the HAstV spike protein, antibody 3H4 targets a novel region near the base of the spike that is more conserved. Additionally, we found that all 3 antibodies bind with high affinity, and they compete with receptor FcRn binding to the capsid spike. These studies inform which regions of the HAstV capsid can be targeted by monoclonal antibody therapies and could aid in rational vaccine design. |
