Ten‐year immune persistence and safety of the HPV‐16/18 AS04‐adjuvanted vaccine in females vaccinated at 15–55 years of age

Abstract

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV‐16/18 from prophylactic vaccination remains unknown. We investigated the 10‐year immune response and long‐term safety profile of the HPV‐16/18 AS04‐adjuvanted vaccine (AS04‐HPV‐16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04‐HPV‐16/18 vaccine in the primary phase‐III study (NCT00196937) were invited to attend annual evaluations for long‐term immunogenicity and safety. Anti‐HPV‐16/18 antibodies in serum and cervico‐vaginal secretions (CVS) were measured using enzyme‐linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow‐up period. Seropositivity rates for anti‐HPV‐16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15–25‐year olds remained seropositive for anti‐HPV‐18 compared to 93.7% and 83.8% of 26–45‐year olds and 45–55‐year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti‐HPV‐16 and anti‐HPV‐18 titers were at least 5.3‐fold and 3.1‐fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti‐HPV‐16/18 antibody titers in subjects aged 15–25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti‐HPV‐16) and 0.38 (anti‐HPV‐18). This study concluded that vaccinated females aged 15–55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long‐term protection against HPV.

Durability of the neutralizing antibody response to vaccine and non-vaccine HPV types 7 years following immunization with either Cervarix® or Gardasil® vaccine

“…All participants remained seropositive to HPV16 following immunization with either vaccine and against HPV18 following immunization with Cervarix®, but seropositivity to HPV18 in the recipients who received the Gardasil® vaccine was lower than 100% after 7 years of follow up. These data are consistent with antibody binding data from 8-9 years of follow up of adolescents [10] or 16 -23 year old women [11] immunized with three doses of Gardasil®, a 10 year follow up study of 15 -25 year old women immunized with three doses of Cervarix® [12] and long term follow up (ca. 12 year) of women enrolled in the Finnish cohorts of the Phase 3 licensure trials of both Cervarix® and Gardasil® vaccines [13].…”

“…A lower vaccine-type seropositivity rate for the neutralizing antibody response in Gardasil® vaccinees was also reported at 5 years in a head to head study of both vaccines in 18 -26 year old women [14]. Lower HPV18 seropositivity rates in Gardasil® vaccinees were evident in both the neutralizing and binding antibody responses reported here but these were higher than the rates reported from other studies [11,12,14] likely due to the younger age of the vaccine recipients in the present study.…”

Human papillomavirus vaccination: The ESGO–EFC position paper of the European society of Gynaecologic Oncology and the European Federation for colposcopy

“…In a substudy of young men aged 16 to 26 years, the observed efficacy against anal disease was 75% for the vaccine types [6]. The clinical efficacy was demonstrated also in women aged from 15 to 45 years [7]; immunogenicity was evaluated in girls and boys from the age of 9 years and for adult women up to the age of 55 years [8]. Based on these data, all three vaccines are licensed by European Medicines Agency (EMA) for girls and boys from the age of 9 years without any upper age limit.…”

The Use of Both Therapeutic and Prophylactic Vaccines in the Therapy of Papillomavirus Disease

“…For anti-HPV18, there were more seropositive females in the 15-to 25-year-old group (99.2%) than for the 26to 45-year-olds (93.7%) and 46-to 55-year-olds (83.8%) (90). In these studies, the anti-HPV16 and anti-HPV18 titers remained above natural infection levels in all of the age groups, and more interestingly, they were predicted to persist for more than 30 years after vaccination (91).…”