Serologic response to human papillomavirus genotypes following vaccination: findings from the HITCH cohort study

Abstract

Background

Human papillomavirus (HPV) infection contributes to approximately 5% of the worldwide cancer burden. The three-dose HPV vaccine has demonstrated immunogenicity and efficacy. Humoral responses may be critical for preventing, controlling, and/or eliminating HPV infection. Using data from the HITCH cohort, we analysed humoral immune response to HPV vaccination among women in relation to the phylogenetic relatedness of HPV genotypes.

Methods

We included 96 women aged 18–24 years attending college or university in Montreal, Canada. Participants provided blood samples at enrolment and five follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S‐transferase fusion proteins of multiple Alphapapillomavirus types, and to virus-like particles (VLP-L1) of HPV16 and HPV18 were measured using multiplex serology. We assessed correlations between antibody seroreactivities using Pearson correlations (r).

Results

At enrolment, 87.7% of participants were unvaccinated, 2.4% had received one, 3.2% two, and 6.7% three doses of HPV vaccine. The corresponding L1 seropositivity to any HPV was 41.2%, 83.3%, 100%, and 97.0%. Between-type correlations for L1 seroreactivities increased with the number of vaccine doses, from one to three. Among the latter, the strongest correlations were observed for HPV58–HPV33 (Pearson correlation [r] = 0.96; α9-species); HPV11–HPV6 (r = 0.96; α10-species); HPV45–HPV18 (r = 0.95; α7-species), and HPV68–HPV59 (r = 0.95; α7-species).

Conclusions

Correlations between HPV-specific antibody seroreactivities are affected by phylogenetic relatedness, with anti-L1 correlations becoming stronger with the number of vaccine doses received.

Keywords:

• Antibodies
• human papillomavirus
• immunogenicity
• papillomavirus vaccines
• serology

Acknowledgments

The authors thank the volunteering participants. The authors also thank Emilie Comète and Julie Guenoun for the processing and laboratory testing of samples, and additional members of the HITCH Cohort Study group: Allita Rodrigues (study coordinator); Hélène Voyer and Véronique Legault (laboratory staff); Gail Kelsall, Suzanne Dumais, Natalia Morykon and Amelia Rocamora (management of subject participation and specimen collection); Nathalie Slavtcheva (study management); Veronika Moravan (data management); Michel Roger (collaborator); Vicky D'Anjou-Pomerleau, Jennifer Selinger, Elizabeth Montpetit-Dubrule, Jessica Sammut, Emilie Lapointe, Johanna Bleecker and Shady Rahayel (study promotion). The authors also thank Melanie Drew (Student Health Services Clinic, Concordia University) and the staff of the Student Health Services Clinics at McGill and Concordia Universities, for their collaboration with HITCH research nurses.

Ethical approval

All subjects provided written informed consent for study participation, and for the storage and use of their specimens in future studies. HITCH follows all national and international regulations regarding research with human data and materials, including the Declaration of Helsinki. The study was conducted in accordance with the principles and articles stipulated by the Tri-Council Policy Statement Ethical Conduct for Research Involving Humans. Ethical approval was obtained from the institutional review boards at McGill University, Concordia University, and Centre Hospitalier de l’Université de Montréal. Ethics renewal approval is requested annually from McGill University (Study Number A09-M77-04A).

Disclosure statement

ELF has served as an occasional advisor to companies involved with human papillomavirus (HPV) diagnostics (Roche, BD, Qiagen, Gen-Probe) and HPV vaccines (Merck, GSK). His institution has received unconditional grants from Merck in aid of investigator-initiated studies. MZ and ELF hold a patent related to the discovery ‘DNA methylation markers for early detection of cervical cancer,’ registered at the Office of Innovation and Partnerships, McGill University, Montreal, Quebec, Canada (October 2018). FC has received grants or free reagents through his institution from Merck Sharp and Dohme, Becton Dickinson and Roche, as well as honoraria from Merck and Roche for lectures on HPV. TW serves on advisory boards for MSD (Merck) Sharp & Dohme. MDW is currently a senior medical writer at Certara Synchrogenix consulting services. All other authors report no potential conflicts of interest. None of the work presented in this manuscript was paid for or influenced by any of the aforementioned companies.

Data availability statement

The data underlying this article will be shared upon reasonable request to ELF.

Additional information

Funding

The HITCH cohort study was supported by the Canadian Institutes of Health Research [CIHR; grant numbers MOP10 68893 and CRN-83320 to ELF]; and the United States National Institutes of Health [grant number RO1AI073889 to ELF]. Supplementary and unconditional funding support was provided by Merck Frosst Canada Ltd, and Merck & Co Ltd. MDW was funded by a CIHR Postdoctoral Fellowship Award [Funding Reference Number: 201611MFE-382677-269048]. SM was funded by a CIHR HIV/AIDS and STBBI Research Initiative, sponsored by the CIHR Institute of Infection and Immunity, Postdoctoral Fellowship Award [Funding Reference Number: 202110HIV-477526-93701]. ANB is a Canada Research Chair in Sexually Transmitted Infection Prevention and a recipient of a University of Toronto Department of Family and Community Medicine non-clinician scientist award. The sponsors did not have a role in designing or conducting the study or writing and publication of the manuscript.