HPV33 and HPV45 sublineage antigenicity defined by neutralizing antibodies elicited during natural infection.

Human Papillomavirus variants are classified into lineages and sublineages based upon their genome sequence, but the impact of variation on the function of encoded proteins is unclear. We used a global panel of natural infection sera and relational antigenic maps to assess HPV33 and HPV45 neutralizing antibody specificity. HPV33 A2, A3, B and C variants were spatially resolved ∼5-fold distant from the A1 reference while HPV45 variants were resolved within ∼2-fold with differences mapped to residues on the capsid surface. These data inform the degree of lineage and sublineage specificity within the natural infection humoral immune response to oncogenic HPV.