Antibody persistence and evidence of immune memory at 5 years following administration of the 9-valent HPV vaccine Ana Guevara a , Robinson Cabello b , Linn Woelber c , Edson Duarte Moreira Jr d , Elmar Joura e , Olaf Reich f , Christine Shields g , Misoo C. Ellison g , Amita Joshi g , Alain Luxembourg g,⇑ a Research Unit, Pablo Tobon Uribe Hospital, Medellin, Antioquia, Colombia b Vía Libre CRS, Jr. Paraguay 490, Lima 01, Peru c University Medical Center Hamburg-Eppendorf, Hamburg, Germany d Associação Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation, Brazilian Ministry of Health, Bahia, Brazil e Medical University of Vienna, Comprehensive Cancer Center, Vienna, Austria f Department of Obstetrics & Gynecology, Medical University of Graz, Austria g Merck & Co., Inc., Kenilworth, NJ, USA article info Article history: Received 28 March 2017 Received in revised form 3 July 2017 Accepted 5 July 2017 Available online 5 August 2017 Keywords: Human papillomavirus 9vHPV vaccine Immunogenicity Clinical trial Immune memory abstract Background: The 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11/16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPV- related vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the genera- tion of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5 years post-vaccination. Methods: A subset of subjects (N = 150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28 days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card. Results: HPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1 week and 1 month post-dose 4 were 1.25–4.10 and 1.65–4.88-fold higher, respectively, than levels observed 1 month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1 week and 1 month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated. Conclusions: A three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5 years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting. Conclusions: Clinical Trials.gov Identifier: NCT00543543. Ó 2017 Elsevier Ltd. All rights reserved. 1. Introduction Human Papillomavirus (HPV) is responsible for 5% of the global cancer burden with including nearly all cervical cancers and a substantial proportion of vulvar, vaginal, anal, penile and oropharyngeal cancers representing >600,000 new cases annually worldwide [1]. HPV infection is also associated with acquisition of anogenital warts [1]. Prophylactic vaccination thus offers the potential to prevent HPV-related cancers and other diseases. A 9- valent HPV (types 6/11/16/18/31/33/45/52/58) (9vHPV) vaccine (Gardasil 9, Merck & Co., Inc., Kenilworth, NJ) was developed to provide protection against the HPV types already covered by the quadrivalent HPV (types 6/11/16/18) (qHPV) vaccine and HPV types 31/33/45/52/58, which are, after HPV types 16/18, the most http://dx.doi.org/10.1016/j.vaccine.2017.07.017 0264-410X/Ó 2017 Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: Merck & Co., Inc., 351N. Sumneytown Pike, North Wales, PA 19454, USA. E-mail address: alain_luxembourg@merck.com (A. Luxembourg). Vaccine 35 (2017) 5050–5057 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine