Structural Superimposition

Abstact

Human papillomavirus type 45 (HPV45) is a high-risk genotype and the third most prevalent HPV type associated with cervical cancer worldwide, posing a significant public health concern. Although HPV45 is included in the commercial 9-valent HPV vaccine, its complete virion structure and the molecular basis of antibody-mediated neutralization remain incompletely understood. Here, we report the near-atomic resolution structure of the HPV45 pseudovirus (PsV45) determined by cryo-electron microscopy. We also isolated and structurally characterized several neutralizing monoclonal antibodies (nAbs) targeting PsV45. Our analysis reveals two distinct neutralizing epitopes on PsV45, and these nAbs likely neutralize the virus by a common mechanism involving the inhibition of viral attachment, despite differences in their binding interfaces. Biochemical assays confirmed that antibodies with non-overlapping binding modes can engage PsV45 simultaneously, indicating potential for synergistic combinations. These findings elucidate the structural basis of HPV45 type specificity and provide insights into HPV neutralization mechanisms.