Role of B cells and formation of immunological memory after vaccination against human papillomavirus

The aim of the present review was to analyze the features of B cell immune response and development of immunological memory in humans after vaccination against human papillomavirus (HPV) and during natural infection, as well as to evaluate the efficiency of various types of vaccines, vaccination regimens and factors affecting the duration of protection against human papillomavirus. The literature review includes an analysis of research papers from the databases PubMed, Embase, eLibrary, CyberLeninka and Web of Science, CNKI and MEDLINE. The search period covered publications from 2000 to 2023, with a focus on the last decade. The following keywords and their combinations were used: "HPV vaccine", "B cell memory", "memory B cells", "humoral immunity", "long-term immunity", "immunological memory", "plasma cells", "Gardasil", "Cervarix". Inclusion and exclusion criteria: The analysis included original studies (randomized controlled, cohort studies) and systematic reviews devoted to the study of the humoral immune response, dynamics of specific antibodies and populations of memory B lymphocytes after HPV vaccination in humans. The exclusion criteria were as follows: publications not in English or Russian; research focused exclusively on T cell immunity; work performed only on animal models; conference abstracts and uncensored articles. Selection procedure: The selection was carried out in two stages: (1) Relevance was assessed based on the title and annotation; (2) A full-text analysis of the articles that passed the primary filter was carried out for final verification of compliance with the inclusion criteria. The final selection included 55 publications that most fully reflect the current understanding of the role of B cells in post-vaccination immunity against HPV. Human papillomavirus is the leading cause of cervical cancer. There are three vaccines: Cervarix (bivalent), Gardasil-4 (quadrivalent) and Gardasil-9 (nonavalent), which show efficiency of >90%. Vaccination reduces the risk of developing cervical cancer and other HPV-related disorders. In 2020, WHO launched a global strategy to eliminate cervical cancer as an important public health problem. The effectiveness of HPV vaccines has been confirmed by clinical and population-based studies. The 4vHPV vaccine reduces the incidence of genital warts by 76%, and prevention of cervical cancer in young women reaches 53-57%. In Finland, vaccination showed 100% protection against HPV-associated cancer in vaccinated people compared to those who were not vaccinated. Twoand three-dose regimens provide comparable protection, and a single-dose regimen has demonstrated 89-100% efficacy in a number of studies. The optimal immune response is achieved by vaccinating children aged 9-13 years with two doses. Despite some observations showing that a single dose of HPV vaccine provides good protection against precancerous lesions, the level of antibodies after one dose is lower than after two or three vaccinations. Protection after a single dose may depend more on the response of memory B cells upon repeated contact with the antigen. However, there are no data concrning B cell response after a single dose of HPV vaccine, as well as sufficient studies of local anamnestic responses upon repeated exposure. It would be a great advance in vaccinology if a single dose of HPV vaccine proved its ability to induce protective B cell memory upon repeated contact with HPV antigens.

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