Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization

Jian Guan, Stephanie M. Bywaters, Sarah A. Brendle, Hyunwook Lee, Robert E. Ashley, Alexander M. Makhov, James F. Conway, Neil D. Christensen, Susan Hafenstein

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope. Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays.

Original languageEnglish (US)
Pages (from-to)253-263
Number of pages11
StatePublished - Sep 1 2015
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. John Schiller for kindly providing HPV16 sheLL and pYSEAP plasmids. This project is funded, in part, under a grant with the Pennsylvania Department of Health using Tobacco CURE Funds . We thank the Microscopy Imaging Core Facility at the Pennsylvania State University College of Medicine. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. The work was supported by Penn State COM Institutional Research Grant #124171-IRG-13-042-01-IRG (SH) , NIH SIG 1S10RR031780-01A1 (SH) , and the Jake Gittlen Memorial Golf Tournament (NC) .

Publisher Copyright:
© 2015 The Authors.


  • Conformation
  • Crosslinking
  • Cryo-EM
  • Epitope
  • HPV16
  • Human papillomavirus
  • MAb
  • Neutralization
  • Stabilization
  • Virus fab complex


Dive into the research topics of 'Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization'. Together they form a unique fingerprint.

Cite this