Impact of Naturally Occurring Variation in the Human Papillomavirus 58 Capsid Proteins on Recognition by Type-Specific Neutralizing Antibodies

Abstract

These data improve our understanding of the impact of natural variation on HPV58 capsid antigenicity and raise the possibility of lineage-specific serotypes.

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

“…Most HPV52 (A2, B1, B2, and C) and HPV58 (A2, A3, B1, B2, D1, and D2) variants exhibited little (<2-fold) or no difference in neutralization sensitivity compared to their respective sublineage A1, whilst HPV52 lineage D and HPV58 lineage C exhibited a >4-fold reduced sensitivity to neutralization by nonavalent vaccine antibodies. The differential recognition of HPV52 D and HPV58 C by nonavalent vaccine sera is in keeping with previously published data on differential sensitivity to natural infection antibodies, preclinical antisera, and L1-specific MAbs for these genotypes [11, 12]. Furthermore, these data suggest that HPV52 D and HPV58 C variants are antigenically distinct from the other lineages within their respective genotypes and should be considered distinct serotypes with respect to nonavalent vaccine-induced immunogenicity.…”

“…Representative variant PsV have previously been created for HPV31, HPV33, HPV45, HPV52, and HPV58 [8–12]. For the present study, lineage variants of HPV16 and HPV18, additional sublineage variants of HPV31 (HPV31 A1, A2, B1, B2) [8], and updated A1 and D2 sublineage variants of HPV58 [12] were created. For HPV16 and HPV18 the consensus lineage A was used as the benchmark sequence while the consensus sublineage A1 was used for the remaining genotypes (Figure 1).…”

“…Inserts were confirmed by Sanger sequencing. Bicistronic psheLL vectors containing these inserts were assembled and with a luciferase reporter (pGL4.51 [luc2/CMV/Neo]; Promega) used to transfect 293TT cells, as previously described [12].…”

“…The pseudovirus (PsV) neutralization assay was performed as previously described [12]. A standardized input of 300 TCID 50 was used for all PsVs.…”

“…The biological consequences of HPV genome variants are unclear. Studies examining the potential impact of natural variation on L1 antigenicity have examined variants of HPV16 [6, 7], HPV31 [8], HPV33 [9], HPV45 [10], HPV52 [11], and HPV58 [12] and demonstrated, in some cases, variant-specific differences in sensitivity to monovalent, bivalent, and quadrivalent VLP immune sera, natural infection sera, and monoclonal antibodies (MAbs). Here, we evaluate the sensitivity of lineage and sublineage variants to neutralization by nonavalent HPV vaccine antibodies.…”