Selective Persistence of HPV Cross-Neutralising Antibodies following Reduced-Dose HPV Vaccine Schedules.

Zheng Quan Toh,Fiona M Russell,Evelyn Tuivaga,Ian H Frazer,Trevelyan Menheniott,Rita Reyburn,Suzanne M Garland,James Fong,Felisita T Ratu,Paul V Licciardi,Lien Anh Ha Do,Silivia Matanitobua,Cattram D Nguyen,Jennie Kosasih,Edward Kim Mulholland

doi:10.3390/vaccines7040200

Abstract

The duration of cross-neutralising antibody responses (cross-NAb) following HPV immunisation is unknown. We compared cross-NAb responses in cohort of girls who were either unimmunised or had received immunisation with one, two or three doses of 4vHPV (Gardasil®, Merck Inc., Kenilworth, NJ, USA) six years earlier, before and one month after a booster dose of 2vHPV (Cervarix®, GSK, Brentford, UK). NAb to potentially cross-reactive HPV genotypes 31, 33, 45, 52 and 58 were measured using a HPV pseudovirion-based neutralisation assay. Girls who had previously received at least one dose of 4vHPV had significantly higher NAb titres for HPV31 when compared with unimmunised girls, whereas no difference in NAb titre was observed for four other genotypes (33, 45, 52 and 58). Following a single further immunisation with 2vHPV, NAb titres to each of the five tested HPV genotypes were comparable for girls who previously received one, two or three doses of 4vHPV, and were significantly higher than for previously unimmunised girls. Immunisation with one, two or three doses of 4vHPV induced NAb to HPV31 that persisted for six years, but there was no persistence of NAb to HPV33, 45, 52 or 58. Our results suggest that one or two doses of 4vHPV may provide long-term protection against HPV31.

Highlights

Introduction6 months) have demonstrated effective protection >96% against human papillomavirus (HPV) type specific cervical cancer precursors in previously uninfected individuals [1,2,3,4,5]
Bivalent (HPV16, 18) (Cervarix® ) and quadrivalent (HPV6, 11, 16, 18) (Gardasil® ) human papillomavirus (HPV) vaccines, when administered in a standard three-dose schedule (0, 1 or 2, and6 months) have demonstrated effective protection >96% against HPV type specific cervical cancer precursors in previously uninfected individuals [1,2,3,4,5]
Six years after the primary immunisation but prior to the booster dose, a significant difference was seen in the seropositivity rates for HPV31 in the girls who received one dose of 4vHPV when compared with three doses, but there were otherwise no significant difference in seropositivity rates between girls who received one or two doses of 4vHPV when compared with girls who received three doses

Summary

Introduction

6 months) have demonstrated effective protection >96% against HPV type specific cervical cancer precursors in previously uninfected individuals [1,2,3,4,5]. Both vaccines induce high levels of vaccine type-specific antibodies that persist for at least 12 years [6]. HPV infection and cervical cancer precursor lesions caused by HPV31/33/45/52/58 in women given three doses of 2vHPV or 4vHPV [9,10,11], a recent post-hoc analysis of Phase III clinical studies have revealed significantly higher efficacy against non-vaccine type high grade cervical lesions in 2HPV when compared with 4vHPV [12]. In countries that have introduced either 2vHPV or 4vHPV immunisation, effectiveness of

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