Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine

doi:10.1016/j.vaccine.2015.08.059

Vaccine

Volume 33, Issue 48, 27 November 2015, Pages 6855-6864

https://doi.org/10.1016/j.vaccine.2015.08.059 Get rights and content

Highlights

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V503-006 was a randomized safety and immunogenicity study in females 12–26 years of age.
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V503-006 evaluated 9vHPV vaccine in those with previous qHPV vaccination.
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9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients.
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9vHPV vaccine was immunogenic for HPV 31/33/45/52/58 in prior qHPV vaccine recipients.

Abstract

Objectives

To assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine.

Methods

V503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12–26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n = 618) or saline placebo (n = 306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA).

Results

The frequency of injection-site AEs (days 1–5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1–15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV = 0.5%; placebo = 0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown.

Conclusions

Administration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12–26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated.

Introduction

A 9-valent HPV (Types 6/11/16/18/31/33/45/52/58) (9vHPV) vaccine has been developed to provide protection against the HPV types already covered by the quadrivalent HPV (types 6/11/16/18) (qHPV) vaccine plus the next five most common oncogenic types (31/33/45/52/58) associated with cervical cancer. Overall, the 9vHPV vaccine offers the potential to prevent approximately 90% of cervical cancers and HPV-related, vulvar, vaginal and anal cancers as well as nearly 90% of genital warts worldwide [1], [2], [3], [4], [5], [6]. In a phase III study, the 9vHPV vaccine prevented ∼97% high-grade cervical, vulvar and vaginal disease associated with HPV 31/33/45/52/58 and elicited non-inferior anti-HPV 6/11/16/18 antibody response compared with qHPV vaccine [7]. The 9vHPV vaccine was licensed in December of 2014 in the United States, in February of 2015 in Canada, and in June of 2015 in the European Union and Australia under the trade name GARDASIL™ 9.

Since the qHPV vaccine's approval in 2006 and through the end of 2014, over 178 million of doses have been distributed worldwide (Merck, data on file). Given the demonstrated protection against oncogenic strains responsible for approximately 20% additional cervical cancer, individuals previously vaccinated may consider that broader protection against HPV is valuable and appropriate and seek additional coverage with the 9vHPV vaccine. Also, health care providers may wonder whether it is safe to administer 9vHPV vaccine to individuals with missing or incomplete vaccination records and who do not remember whether or not they previously received HPV vaccination. In anticipation of such situations, a study was conducted to describe the safety and immunogenicity profile of the 9vHPV vaccine administered to prior qHPV vaccine recipients.

Section snippets

Study and population

This study (Protocol V503-006, NCT# NCT01047345) was a double-blinded, placebo-controlled, safety and immunogenicity study of the 9vHPV vaccine in girls and women 12–26 years of age who previously received a 3-dose regimen of qHPV vaccine. The study was initiated in February 2010 and was completed in June 2011. Subjects were enrolled from 32 study sites and 8 countries (Australia, Canada, Colombia, Denmark, Hong Kong, Mexico, Sweden, United States [including Puerto Rico]). The study was

Study population

A total of 935 subjects were screened for inclusion in this study and 924 were randomized, including 618 subjects in the 9vHPV vaccine group and 306 subjects in the placebo group. The numbers of subjects who were randomized, vaccinated, and completed or discontinued the study are provided in Fig. 1.

As seen in Table 1, the 2 vaccination groups were comparable with respect to age, geographic region, and race. Most subjects (99%) had received a 3-dose regimen of qHPV vaccine within a 1-year period

Discussion

The safety and immunogenicity of a 3-dose regimen of the 9vHPV vaccine was analyzed in girls and women 12–26 years of age who had previously received a 3-dose regimen of qHPV vaccine. The 9vHPV vaccine was generally well tolerated in this population. Discontinuations and vaccine-related serious AEs were rare. Injection-site AEs were mostly mild or moderate in intensity. Injection-site AEs occurred more frequently in the 9vHPV vaccine group than in the placebo group; given that a saline placebo

Acknowledgements

Investigators (who are not also authors): (Australia) Ferdinandus Johan de Looze, (Canada) Marie-Claude Audet, Celine Bouchard, Barry Dworkin, (Colombia) Alfonso Correa, Jaime Alberto Restrepo, Humberto Reynales, (Denmark) Erik Sogaard Andersen, Jesper Mehlsen, Ole Mogensen, Soren Toubro, (Hong Kong) Hextan Ngan, (Sweden) Kristiina Kask, Agneta Moller, Sven-Eric Olsson, Jan Wall, Charlotte Wallgren, (United States) Shane Christensen, Matthew Davis, Daron Ferris, Stanley Gall, Katie Ann Julien,

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View all citing articles on Scopus

^☆: NCT# NCT01047345.

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Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine☆

Highlights

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Study and population

Study population

Discussion

Acknowledgements

Lancet Oncol

Eur J Cancer

Eur J Cancer

Vaccine

Virology

Vaccine

Vaccine

Vaccine

Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease

Infect Agent Cancer

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide

Int J Cancer

9-valent HPV vaccine against infection and intraepithelial neoplasia in women

N Engl J Med

Development of a human papillomavirus competitive Luminex immunoassay for 9 HPV types

Hum Vaccines Immunother

The use of confidence or fiducial limits illustrated in the case of the binomial

Biometrika