Sustained Immunogenicity of 2-dose Human Papillomavirus 16/18 AS04-adjuvanted Vaccine Schedules in Girls Aged 9–14 Years: A Randomized Trial

Huang, Li‐Min; Puthanakit, Thanyawee; Chiu, Cheng-Hsun; Tang, Ren-Bin; Schwarz, Tino F.; Pellegrino, Angelo; Esposito, Susanna; Frenette, Louise; McNeil, Shelly; Durando, Paolo; Rheault, Paul; Giaquinto, Carlo; Horn, Michael; Petry, Karl Ulrich; Peters, Klaus; Toma, Aurel; Hillemanns, Peter; Simoni, Stéphanie De; Friel, Damien; Pemmaraju, Suryakiran; Hezareh, Marjan; Thomas, Florence; Descamps, Dominique; Folschweiller, Nicolas; Struyf, Frank

doi:10.1093/infdis/jix154

Cited by 21 publications

(21 citation statements)

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“…This is consistent with previous findings reported by Romanowski et al, which showed that 2 doses of bHPV (spaced at 6 months) produced an immune response that persists for up to 5 years of follow-up [ 10 ]. Although our antibody responses differ slightly from those reported by Romanowski et al [ 10 ] and Huang et al [ 12 ], who used the same serological assay, our findings support evidence of the high and strong immune response in girls who received <3 doses. In comparing antibody response among different studies, it should be taken into account the difference in participants and study designs, as well as differences between laboratories and kit lots for VLP-based ELISAs.…”

Section: Discussionsupporting

confidence: 66%

Persistence of Immunity When Using Different Human Papillomavirus Vaccination Schedules and Booster-Dose Effects 5 Years After Primary Vaccination

Lazcano‐Ponce¹,

Torres‐Ibarra²,

Cruz-Valdéz³

et al. 2018

The Journal of Infectious Diseases

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BackgroundThere are limited data regarding the duration of immunity induced by different human papillomavirus (HPV) vaccination schedules and the immunogenicity of a booster dose of both bivalent HPV vaccine (bHPV) or quadrivalent HPV vaccine (qHPV).MethodsFollow-up of a nonrandomized clinical trial to evaluate the 5-year antibody persistence of the bHPV in girls (age, 9–10 years) and women (age, 18–24 years). Noninferiority of the 2-dose versus 3-dose schedule among girls was evaluated at months 54 (n = 639) and 64 (n = 990). Girls vaccinated with a 2-dose schedule of bHPV or qHPV received a booster dose of either vaccine at month 61. Immunogenicity was measured using a virus-like particle–based enzyme-linked immunosorbent assay. Geometric mean titers (GMTs) for HPV16/18 were estimated after stratification by vaccination schedule and age group.ResultsAt months 54 and 64, the 2-dose schedule remained noninferior to the 3-dose schedule. GMTs remained above natural infection levels across all age groups up to 64 months. After the booster, anti-HPV16/18 GMTs increased exponentially with the same pattern, regardless of vaccine administered. No safety concerns were identified with the booster dose.ConclusionsA 2-dose schedule is highly immunogenic in girls, suggesting a high immune memory. Thus, a booster dose is likely to be unprofitable, considering the low global immunization coverage.Clinical Trials RegistrationNCT01717118

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Section: Discussionsupporting

confidence: 66%

Persistence of Immunity When Using Different Human Papillomavirus Vaccination Schedules and Booster-Dose Effects 5 Years After Primary Vaccination

Lazcano‐Ponce¹,

Torres‐Ibarra²,

Cruz-Valdéz³

et al. 2018

The Journal of Infectious Diseases

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“…The reduced dose schedule from 3-dose to 2-dose for the young adolescent population was based on the evidence that the 2-dose regimens in young adolescent girls showed an equivalent immune response to the 3-dose regimen in 15-25 years old females in terms of magnitude and durability of the immune response. 40,41 Studies following vaccinated individuals for 6-12 years suggested that 3-dose HPV vaccines offer long-term protection against HPV infection and HPVrelated diseases. [42][43][44] However, whether the duration of protection can cover the entire sexually active life expectancy and whether a boost dose is required remained to be studied.…”

Section: Discussionmentioning

confidence: 99%

A ten-year study of immunogenicity and safety of the AS04-HPV-16/18 vaccine in adolescent girls aged 10-14 years

Schwarz

Huang

Valencia

et al. 2019

Human Vaccines & Immunotherapeutics

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This study assessed long-term immunogenicity and safety following 3 doses of AS04-adjuvanted human papillomavirus (HPV)-16/18 L1 virus-like particle (VLP) vaccine in females 10-14 years old. Girls included in the immunogenicity subset in the primary controlled, observer-blinded, randomized study (NCT00196924) who received 3 doses were invited for a 10-year follow-up (NCT00316706 and NCT00877877). Serum antibody responses against HPV-16/18 (vaccine types) and HPV-31/45 (nonvaccine types) were measured by enzyme-linked immunosorbent assay (ELISA) using type-specific VLP as coating antigens. Serious adverse events (SAEs) and pregnancy information were recorded. At Month (M) 120, all subjects (N = 418, according-to-protocol immunogenicity cohort) were seropositive for anti-HPV-16/18 antibodies. Geometric mean titers (GMTs) were 1589.9 ELISA Units [EU]/mL (95% confidence interval [CI]: 1459.8-1731.6) for anti-HPV-16 and 597.2 EU/mL (95% CI: 541.7-658.5) for anti-HPV-18 in subjects seronegative at baseline for the type analyzed. Post hoc mathematical modeling predicted a durability ≥50 years for anti-HPV-16 and anti-HPV-18. For the non-vaccine humoral type response, all initially seronegative subjects had seroconverted at M7, with anti-HPV-31 GMT of 2030.5 EU/mL (95% CI: 1766.2-2334.4) and anti-HPV-45 GMT of 2300.8 EU/mL (95% CI: 2036.8-2599.0). At M120, 87.7% and 85.1% remained seropositive for anti-HPV-31 with GMT of 242.9 EU/mL (95% CI: 201.4-293.0) and anti-HPV-45 with GMT of 204.7 EU/mL (95% CI: 170.0-246.6). During the 10-year follow-up, no SAEs or abnormal pregnancy outcomes were causally related to vaccination. Three doses of the AS04-HPV-16/18 vaccine induced high and sustained antibody response against HPV-16,18,31 and 45 in girls aged 10-14 years during the 10-year follow-up, with an acceptable long-term safety profile.

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“…Clinical trials in pediatric populations are conducted in those individuals who stand to potentially benefit from the treatment. Healthy children participate in studies such as immunization trials against diseases that they might reasonably be expected to contract or postapproval assessment of nutritional supplements . Reasonably stable children with the target disease participate in clinical pharmacology studies as well as in clinical studies of medications used to treat diseases that occur only in children .…”

Section: General Study Considerations For Pediatric Subjectsmentioning

confidence: 99%

The Path to Perfect Pediatric Posology — Drug Development in Pediatrics

Korth‐Bradley

2018

The Journal of Clinical Pharma

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Reluctance to enroll pediatric subjects in clinical trials has left gaps in information about dosing, safety, and efficacy of medications. Pharmacotherapeutic information for pediatric patients may be available for only a small range of ages and may be deficient, as children respond differently as they grow and mature from prematurity to adolescence. Current regulations, however, require early planning for the participation of children in drug development, as pediatric plans must be submitted at the end of phase 1 (European Union) or the end of phase 2 (United States). These plans are extensive, outlining planned studies, subjects to be enrolled, dose and dosage form justification, planned observations, and statistical analysis as well as planned modeling, simulation, and extrapolation analyses. The extent to which efficacy information in adults can be extrapolated to children depends on how similar the disease is in adults and each of the 5 pediatric age groups. Extrapolation may not be possible for conditions that do not occur in adults, requiring a complete development plan in adults, or extrapolation may be complete because of similar pathology and response to treatment. Pharmacokinetic and safety information cannot be extrapolated and must be collected in children of all ages, unless a waiver is granted. Physiologically based pharmacokinetic modeling, optimal design, population pharmacokinetics, and scavenged samples are all examples of new methodologies being used to study pediatric therapeutics. Clinicaltrials.gov and EU Clinical Trials registry are good sources of results of pediatric trials, although sponsors are also working toward prompt publication of study results in peer‐reviewed journals.

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Sustained Immunogenicity of 2-dose Human Papillomavirus 16/18 AS04-adjuvanted Vaccine Schedules in Girls Aged 9–14 Years: A Randomized Trial

Abstract: SummaryHuman papillomavirus vaccination began using a 3-dose schedule. Compared with the 3-dose schedule in women, the 2-dose schedules are effective options in young girls as of 36 months after first dose. Two-dose schedules could improve compliance and vaccination coverage.

Cited by 21 publications

References 32 publications

Persistence of Immunity When Using Different Human Papillomavirus Vaccination Schedules and Booster-Dose Effects 5 Years After Primary Vaccination

Persistence of Immunity When Using Different Human Papillomavirus Vaccination Schedules and Booster-Dose Effects 5 Years After Primary Vaccination

A ten-year study of immunogenicity and safety of the AS04-HPV-16/18 vaccine in adolescent girls aged 10-14 years

The Path to Perfect Pediatric Posology — Drug Development in Pediatrics

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