Post-hoc analysis from phase III trials of human papillomavirus vaccines: considerations on impact on non-vaccine types

Ryser, Martin; Berlaimont, Valérie; Karkada, Naveen; Mihályi, Attila; Rappuoli, Rino; Most, Robbert van der

doi:10.1080/14760584.2019.1579647

Cited by 18 publications

(22 citation statements)

References 52 publications

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“…Taken together these data might suggest that, despite the low levels of non-vaccine type antibodies elicited by the HPV vaccines, it is their specificity that distinguishes them from type-specific antibodies elicited by natural infection and contributes to the vaccine effectiveness against nonvaccine types observed in vaccine trials and impact studies [2,5]. A recent review [25] and post-hoc analysis of vaccine efficacy data [26] have attempted to delineate possible mechanism(s) behind the potency of the HPV vaccines, including the activation of additional immune pathways and uncertainty about the levels and site of action of these immune effectors. The role that neutralizing antibodies play in the long-term protection against infection and subsequent disease is uncertain and the utility of such antibodies as a potential correlate or surrogate of such protection in unclear.…”

Section: Discussionmentioning

confidence: 99%

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

Godi

Panwar

Haque

et al. 2019

Vaccine

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Bivalent (Cervarix®) and quadrivalent (Gardasil®) Human Papillomavirus (HPV) vaccines demonstrate remarkable efficacy against the targeted genotypes, HPV16 and HPV18, but also a degree of cross-protection against non-vaccine incorporated genotypes, HPV31 and HPV45. These outcomes seem to be supported by observations that the HPV vaccines induce high titer neutralizing antibodies against vaccine types and lower responses against non-vaccine types. Few data are available on the robustness of the immune response against non-vaccine types. We examined the durability of vaccine and non-vaccine antibody responses in a follow up of a head-tohead study of 12-15 year old girls initially randomized to receive three doses of Cervarix® or Gardasil® vaccine. Neutralizing antibodies against both vaccine and non-vaccine types remained detectable up to 7 years following initial vaccination and a mixed effects model was used to predict the decline in antibody titers over a 15 year period. The decline in vaccine and non-vaccine type neutralizing antibody titers over the study period was estimated to be 30% every 5-7 years, with Cervarix® antibody titers expected to remain 3-4 fold higher than Gardasil® antibody titers over the long term. The antibody decline rates in those with an initial response to non-vaccine types were similar to that of vaccine types and are predicted to remain detectable for many years. Empirical data on the breadth, magnitude, specificity and durability of the immune response elicited by the HPV vaccines contribute to improving the evidence base supporting this important public health intervention. Original trial: ClinicalTrials.gov NCT00956553

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Section: Discussionmentioning

confidence: 99%

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

Godi

Panwar

Haque

et al. 2019

Vaccine

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“…Similarly, the incidence of a7, a9, and a10 HPV types was significantly lower in male partners of vaccinated women. Previous studies have reported cross-type protection from HPV vaccines via induction of cross-neutralizing antibodies (24)(25)(26)(27)(28). It is conceivable that this effect on the humoral immune response would ultimately alter the transmission dynamics of HPV types of the a7, a9, and a10 species not included in the vaccines.…”

Section: Discussionmentioning

confidence: 99%

Vaccination of Young Women Decreases Human Papillomavirus Transmission in Heterosexual Couples: Findings from the HITCH Cohort Study

Wissing

Burchell

El‐Zein

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Vaccination against human papillomaviruses (HPV) prevents HPV infections and, consequently, cervical lesions. However, the effect of vaccination on HPV transmission within couples is unknown. Methods: We used data from HITCH, a prospective cohort study of heterosexual couples (women ages 18-24 years) in Montreal, 2005 to 2013. Vaccination history was selfreported. Genital samples were tested for HPV DNA by PCR (linear array). Type-specific viral loads were quantified using real-time PCR. OR and HR were estimated using multilevel mixed-effects logistic regression and a parametric model for interval-censored survival-time data, respectively. Differences in viral loads were evaluated using the Friedman ANOVA test. Results: Among 497 couples, 12, 16, and 35 women received 1, 2, or 3 vaccination doses at baseline, respectively. Median age at vaccination was 18 years. Most women (92.1%) had their first coitus before vaccination. At baseline, partner concordance of persistent HPV6/11/16/18 infections was lower in vaccinated than unvaccinated women [adjusted OR ¼ 0.10; 95% confidence interval (CI), 0.01-0.65] but not for non a7/a9/a10-HPV types (adjusted OR ¼ 1.00; 95% CI, 0.44-2.29). Incidence of persistent a7/a9/a10 HPV types in women was inversely associated with vaccination status at baseline (adjusted HR ¼ 0.12; 95% CI, 0.03-0.47). Likewise, male partners of vaccinated women had a lower incidence of a7/a9/a10 HPV infections (adjusted OR ¼ 0.22; 95% CI, 0.05-0.95). Vaccinated women with HPV 6/11/16/18 infections had lower viral loads (P ¼ 0.001) relative to unvaccinated women. Conclusions: Vaccination of sexually active women significantly reduced transmission of a7/a9/a10 HPV types in heterosexual couples. Impact: These results underscore and quantify the positive effect of HPV vaccination on HPV transmission within heterosexual couples.

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“…15 Based on the evidence available to date, the protection provided by the AS04-HPV-16/18 vaccine against HPV types other than 16/18 is presumably due to the adjuvant system. [16][17][18] As the risk of cervical HPV infection is related to sexual activity and considering the prophylactic nature of the HPV vaccines, 19,20 vaccination should occur before onset of sexual activity. 21 Long-lasting protection is, however, crucial to protect girls and women during the early years of their sexual activity when the risk of infection is the highest.…”

Section: Introductionmentioning

confidence: 99%

Long‐term persistence of immune response to the AS04‐adjuvanted HPV‐16/18 vaccine in Chinese girls aged 9‐17 years: Results from an 8‐9‐year follow‐up phase III open‐label study

Zhang²,

He³

et al. 2020

Asia-Pac J Clncl Oncology

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Aim: In 9-17-year-old Chinese girls, the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18) given as three-dose schedule induced high antibody levels, which were noninferior 1 month after the third dose to those observed in 18-25-year-old Chinese women in a large efficacy study. We assessed the persistence of antibodies 8-9 years after vaccination in the same subjects. Methods: This follow-up phase III, open-label study (NCT03355820) included subjects who had received three doses of AS04-HPV-16/18 in the initial trial (NCT00996125). Serum antibody concentrations were assessed by ELISA and compared to antibody persistence observed in 18-25-year-old Chinese women 6 years after first vaccination in the efficacy study (NCT00779766). Results: Out of the 227 enrolled subjects, 223 were included in the per-protocol immunogenicity analysis. Mean interval from first AS04-HPV-16/18 dose to blood sampling was 101.4 months (8.5 years). For antibodies against HPV-16 and-18, 8.5 years after first vaccine dose all subjects remained seropositive and antibody. Geometric mean concentrations (GMCs) were 1236.3 (95% confidence interval [CI]: 1121.8; 1362.4) and 535.6 (95% CI: 478.6; 599.4) ELISA Units/mL, respectively. These seropositivity rates and antibody GMCs were higher than those observed 6 years after first vaccination of 18-25-year-old women. Conclusion: Sustained anti-HPV-16 and-18 immune responses were observed 8-9 years after AS04-HPV-16/18 vaccination of 9-17 year-old Chinese girls that were higher than the ones observed 6 years after first vaccination in Chinese adult women This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Post-hoc analysis from phase III trials of human papillomavirus vaccines: considerations on impact on non-vaccine types

Cited by 18 publications

References 52 publications

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

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

Vaccination of Young Women Decreases Human Papillomavirus Transmission in Heterosexual Couples: Findings from the HITCH Cohort Study

Long‐term persistence of immune response to the AS04‐adjuvanted HPV‐16/18 vaccine in Chinese girls aged 9‐17 years: Results from an 8‐9‐year follow‐up phase III open‐label study

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