Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects

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.

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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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). https://doi.org/10.1134/S0006297919070101

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Keywords

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