Long‐term persistence of systemic and mucosal immune response to HPV‐16/18 AS04‐adjuvanted vaccine in preteen/adolescent girls and young women

Abstract

Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered to young women aged 10-25 years. Serum and cervicovaginal secretion (CVS) samples were collected at prespecified time-points during the 48-month follow-up period. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay (ELISA). At Month 48, all subjects remained seropositive for serum anti-HPV-16 and -18 antibodies. As previously observed, anti-HPV-16 and -18 antibodies levels (ELISA Units/mL) were higher in subjects vaccinated at the age of 10-14 years (2862.2 and 940.8) compared to subjects vaccinated at the age of 15-25 years (1186.2 and 469.8). Moreover, anti-HPV-16 and -18 antibodies in CVS were still detectable for subjects aged 15-25 years (84.1% and 69.7%, respectively). There was a strong correlation between serum and CVS anti-HPV-16 and -18 antibodies levels (correlation coefficients 5 0.84 and 0.90 at Month 48, respectively) supporting the hypothesis of transudation or exudation of serum immunoglobulin G antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to 4 years after the first vaccine dose.Cervical cancer is the second most common cancer among women worldwide, with nearly 500,000 new cases and approximately 270,000 deaths each year. 1,2 Human papillomavirus (HPV) infection with oncogenic types is well recognized as the necessary cause of virtually all cervical cancers, and HPV DNA has been found in 99.7% of all cases. 2-4 HPV types 16 and 18 are the most common oncogenic HPV types, responsible for about 70% of all cervical cancers. 5,6

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

“…Antibody kinetics had similar profiles across all age groups, displaying a decline in GMT values with increasing ages at first vaccination. As previously observed in the same study, a more or less potent correlation was observed between the anti‐HPV‐16/18 antibody levels in the serum and CVS samples, further supporting the previous observation of long‐lasting transudation of serum antibodies across the cervical epithelium, although this association was not as strong as that seen at the Year 6 time point and was quite weak for HPV‐18, presumably as a result of a smaller number of evaluable samples at the Year 10 time point 10, 18, 23.…”

Long-term Immunogenicity and Safety of the HPV-16/18 AS04-adjuvanted Vaccine in 10- to 14-year-old Girls

“…35,36 Anti-HPV-16 and -18 antibody levels induced by the HPV-16/18 AS04-adjuvanted vaccine were maintained for up to 6 years postvaccination at much higher levels (at least 33-fold) than the antibody levels associated with natural infection, which is in line with previous studies. 18,21,22,25,26,29,31 Naturally acquired anti-HPV antibody seroconversion was previously found to be insufficient to protect against reinfection with homologous human papillomavirus types. 34 Nevertheless, a recent study showed that individuals with high naturally acquired anti-HPV-16 antibody titers were likely to be protected against HPV-16 reinfection and its associated atypical squamous cells of undetermined significance.…”

“…29 The kinetics of anti-HPV-16 and -18 antibody titers were similar to those observed in previous clinical trials, with antibody GMTs showing a peak response after the administration of the third vaccine dose, which then declined to reach a plateau approximately 18-24 months after the first vaccination. 13,15,18,21,22,26,31 Production of high and sustained antibody titers through vaccination could be assumed to be predictive of long-term protection against oncogenic human papillomavirus infections and [32][33][34] Although this study was not designed to assess efficacy, anti-HPV-16 and -18 antibody levels in adolescent girls at 6 years postvaccination were severalfold higher than the plateau levels observed in young adult women in a previous study, in which sustained efficacy of the HPV-16/18 AS04-adjuvanted vaccine against cervical lesions and infections was demonstrated. [13][14][15]18,21,22 These findings were consistent with the results of the initial study and its followup period up to 4 years postvaccination 27,28 and were expected since immune responses to vaccination are known to be higher in younger populations.…”

“…24 In preteen/adolescent girls aged 9-14 years, ie, the primary targeted population for organized vaccination programs, immune responses induced by the HPV-16/18 AS04-adjuvanted vaccine have been shown to be approximately 2-fold higher than in young adult women. [25][26][27][28] The enhanced immune responses observed in preteen/adolescent girls may predict a longer persistence of high antibody levels in younger age populations.…”

Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point—registry-based follow-up ofthree cohorts from randomized trials

“…4 13 In addition, 64 16-17 year olds received 3 doses of the HPV-16/18 vaccine by May 2005 in a concomitant HPV-012 trial which ended 4 years later. 15 Following the end of the active follow-up in May 2009, approximately 50% of the HAV-vaccine recipients chose HPV-16/18 cross-vaccination during 2009-2010. HrHPV DNA positives at the last PATRICIA trial visit (215 from the HPV-16/18 cohort and 318 from the HAV cohort) continued active clinical follow-up (HPV-052 study protocol) for approximately 1.9 years after the end of the PATRICIA trial.…”