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REVIEW: Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects

M. S. Vonsky1,2,a, A. L. Runov1,2,3, I. V. Gordeychuk3,4,5,b, and M. G. Isaguliants3,4,6,7,c*

1Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia

2Almazov National Medical Research Centre, Ministry of Health of Russian Federation, 197341 St. Petersburg, Russia

3Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of Russian Federation, 123098 Moscow, Russia

4Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences, 108819 Moscow, Russia

5Sechenov First Moscow State Medical University, Ministry of Health of Russian Federation, 119991 Moscow, Russia

6Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology, SE-171 77 Stockholm, Sweden

7Riga Stradins University, Department of Pathology, LV-1007 Riga, Latvia

* To whom correspondence should be addressed.

Received April 3, 2019; Revised April 15, 2019; Accepted April 21, 2019
Human papillomaviruses of high carcinogenic risk (HR HPVs) are major etiological agents of malignant diseases of the cervix, vulva, penis, anal canal, larynx, head, and neck. Prophylactic vaccination against HPV, which mainly covers girls and women under 25, does not prevent vertical and horizontal HPV transmission in infants and children and does not have a therapeutic effect. As a result, a significant proportion of the population is not protected from the HPV infection and development of HPV-associated neoplastic transformation and cancer, which indicates the need for development and introduction of therapeutic HPV vaccines. Unlike prophylactic vaccines aimed at the formation of virus-neutralizing antibodies, therapeutic vaccines elicit cellular immune response leading to the elimination of infected and malignant cells expressing viral proteins. The ideal targets for vaccine immunotherapy are highly conserved HR HPV oncoproteins E6 and E7 expressed in precancerous and tumor tissues. Here, we describe expression of these proteins during different stages of HPV infection, their antigenic and immunogenic properties, and T-cell epitopes, the response to which correlates with natural regression of HPV-induced neoplastic changes. The review describes patterns of E6 and E7 oncoproteins presentation to the immune system as components of candidate vaccines along with the results of the most promising preclinical trials and animal models used in these trials. Special attention is paid to vaccine candidates which have shown efficacy in clinical trials in patients with HPV-associated neoplastic changes.
KEY WORDS: human papillomavirus, squamous cell carcinoma, neoplasia, E6 and E7 oncoproteins, therapeutic vaccination, genetic vaccines, immune response

DOI: 10.1134/S0006297919070101