Natural and vaccine-induced B cell-derived systemic and mucosal humoral immunity to human papillomavirus

ABSTRACT

Introduction

Human papillomavirus (HPV) are the causative agent of mucosal neoplasia. Both cervical, anal and oropharyngeal cancers incidence is constantly increasing, making the HPV infection, a significant worldwide concern. Together, the CD8+ T cytotoxic cell-mediated response and the HPV-specific antibody response control most of the HPV infections before the development of cancers.

Areas covered

We searched the MEDLINE and EMBASE databases and identified 228 eligible studies from 1987 to 2019 which examines both naturally acquired and vaccine induced humoral immunity against HPV infection in female and male subjects from worldwide origin. Herein, we synthesize current knowledge on the features of systemic and mucosal humoral immunity against HPV. We discuss the issues of the balance between the viral clearance or the escape to the host immune response, the differences between natural and vaccine-induced HPV-specific antibodies and their neutralizing capability. We also discuss the protection afforded after natural infection or following prophylactic vaccination.

Expert opinion

Understanding the antibody response induced by HPV infection has led to the design of first-generation prophylactic vaccines. Now, prophylactic vaccination induces protective and long-lasting antibody response which would also strengthened the natural moderate humoral response in people previously exposed to the virus.

KEYWORDS:

• Human papillomavirus infection
• HPV-associated cancers
• Natural and vaccine-induced humoral immune responses
• Virus-like particle HPV prophylactic vaccine
• Neutralizing antibody

Article highlights

• Naturally acquired HPV-type specific antibodies provide modest protection against subsequent infections for women, but not for men.

• Several men and women exhibiting humoral immunity following natural HPV infection are still, nevertheless, at risk for subsequent or recurrent HPV infections and associated cancers.

• The impact of HIV on the protective effect conferred by the naturally acquired HPV-type specific antibodies is still unclear.

• The current approved three prophylactic vaccines, Cervarix®, Gardasil-4®, and Gardasil-9® are all strongly immunogenic and induced high and persistent titers of anti-HPV antibodies highly type-specific and also cross-reactive, both in the serum and in the mucosal compartments. Thus, this vaccine-induced humoral response confers a strong and durable protection against subsequent and recurrent HPV infections in young girls and boys.

• However, some concerns arise about the vaccination with these three vaccines. Firstly, the decline of vaccine-induced antibody to HPV18 and related phylogenetic types suggest a possible progressive loss of the protection elicited against these HPV, after vaccination with both the two Gardasil® vaccines. On the other hand, there is an urgent necessity to reduce the dose schedule from a 6-month 3-dose schedule to a unique but highly immunogenic and protective dose.

• The extension of the age of vaccination should be also thoroughly studied for a possible extension from the current recommendation (9–14 years old) to a possible recommendation of age vaccination well beyond the age of 25 years to 35/40 years old, both for adult women and men which are the most at-risk age group for HPV-related cancers.

• Along with a reduced dose schedule, a vaccination program including young adult individuals (25–40 years old) and also individuals with preexisting HPV infection markers (HPV DNA positivity and/or anti-HPV antibodies seropositivity) would be a great alternative for extending the vaccine coverage. Particularly in countries with limited resources which are also both the countries where the current vaccination recommendations are difficult to be implemented and also those with the highest prevalence and incidence of HPV infection and related cancers. These alternatives could help to broaden the herd immunity against HPV in the most at-risk population living in the most at-risk areas.

Acknowledgments

Ralph-Sydney Mboumba Bouassa is a PhD student from the Ecole Doctorale en Infectiologie Tropicale, Franceville, Gabon, benefiting from a scholarship of the Gabonese Government and is holder of merit from the Agence Universitaire de la Francophonie. Mohammad-Ali Jenabian is the holder of the tier 2 Canada research chair in immune-virology.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.