Sensitivity of Human Papillomavirus (HPV) Lineage and Sublineage Variant Pseudoviruses to Neutralization by Nonavalent Vaccine Antibodies

Natural variants of human papillomavirus (HPV) are classified into lineages and sublineages based upon whole-genome sequence, but the impact of diversity on protein function is unclear. We investigated the susceptibility of 3-8 representative pseudovirus variants of HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, and HPV58 to neutralization by nonavalent vaccine (Gardasil®9) sera. Many variants demonstrated significant differences in neutralization sensitivity from their consensus A/A1 variant but these were of a low magnitude. HPV52 D and HPV58 C variants exhibited >4-fold reduced sensitivities compared to their consensus A/A1 variant and should be considered distinct serotypes with respect to nonavalent vaccine-induced immunity.