Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects


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 intro- duction 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.



antigen-presenting cell


cervical cancer


cytotoxic T-lymphocyte


dendritic cell


human leukocyte antigen


human papillomavirus of high carcinogenic risk


high grade squamous intraepithelial lesion


immune checkpoint inhibitor


listeriolysin O


low-grade squamous intraepithelial lesion


main histocompatibility complex


modified vaccinia virus Ankara


open reading frame


squamous cell carcinoma of the head and neck


Semliki Forest virus


long (including overlapping) synthetic peptides


tumor associated antigen


T-cell receptor


toll-like receptor


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Correspondence to M. S. Vonsky or M. G. Isaguliants.

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Russian Text © The Author(s), 2019, published in Biokhimiya, 2019, Vol. 84, No. 7, pp. 1016–1035.

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Vonsky, M.S., Runov, A.L., Gordeychuk, I.V. et al. Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects. Biochemistry Moscow 84, 800–816 (2019).

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  • human papillomavirus
  • squamous cell carcinoma
  • neoplasia
  • E6 and E7 oncoproteins
  • therapeutic vaccination
  • genetic vaccines
  • immune response