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Biochemistry (Moscow)

, Volume 84, Issue 7, pp 800–816 | Cite as

Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects

  • M. S. VonskyEmail author
  • A. L. Runov
  • I. V. Gordeychuk
  • M. G. IsaguliantsEmail author
Review

Abstract

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.

Keywords

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

Abbreviations

APC

antigen-presenting cell

CC

cervical cancer

CTL

cytotoxic T-lymphocyte

DC

dendritic cell

HLA

human leukocyte antigen

HR HPV

human papillomavirus of high carcinogenic risk

HSIL

high grade squamous intraepithelial lesion

ICI

immune checkpoint inhibitor

LLO

listeriolysin O

LSIL

low-grade squamous intraepithelial lesion

MHC

main histocompatibility complex

MVA

modified vaccinia virus Ankara

ORF

open reading frame

SCCHN

squamous cell carcinoma of the head and neck

SFV

Semliki Forest virus

SLPs

long (including overlapping) synthetic peptides

TAA

tumor associated antigen

TCR

T-cell receptor

TLR

toll-like receptor

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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  1. 1.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia
  2. 2.Almazov National Medical Research CentreMinistry of Health of Russian FederationSt. PetersburgRussia
  3. 3.Gamaleya National Research Center for Epidemiology and MicrobiologyMinistry of Health of Russian FederationMoscowRussia
  4. 4.Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological ProductsRussian Academy of SciencesMoscowRussia
  5. 5.Sechenov First Moscow State Medical UniversityMinistry of Health of Russian FederationMoscowRussia
  6. 6.Karolinska Institutet, Department of MicrobiologyTumor and Cell BiologyStockholmSweden
  7. 7.Department of PathologyRiga Stradins UniversityRigaLatvia

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